Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest...

53
Does nature affect human immune function? Qing Li, MD, PhD Nippon Medical School Tokyo, Japan May 27, 2011

Transcript of Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest...

Page 1: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Does nature affect human immune function

Qing Li MD PhDNippon Medical School

Tokyo Japan

May 27 2011

What are natural environments(green spaces)

There are numerous definitions of natural environments (also called green spaces)

The Centres for Disease Control define them as ldquoopen undeveloped land with natural vegetationrdquo parks forests playing fields river corridors and the like

Nature is defined as bdquothe environment in which organisms or their biotopes expressly manifest themselves In addition to nature reserves this also includes farmland production forest urban green spaces and back gardens‟ (Health Council of the Netherlands 2004)

What is a forest

In 2000 the Forest Resources Assessment (FRA) 2000 project defined the ldquoforestrdquo as follows

Forest includes natural forests and forest plantations

It is used to refer to land with a tree canopy cover of more than 10 percent and area of more than 05 ha (hectare)

Forests are determined both by the presence of trees and the absence of other predominant land uses

The trees should be able to reach a minimum height of 5 m

httpwwwfaoorgDOCREP004Y1997Ey1997e1mhtm

What is a forest in Japan

In Japan forest is used to refer to land with a tree canopy cover of more than 30 percent and area of more than 03 ha (hectare)

The trees should be able to reach a minimum height of 5 m with a width of more than 20 m

The forests include Japanese cypress (Chamaecyparisobtuse Hinoki in Japanese) Japanese cedar (Cryptomeria Sugi in Japanese) Japanese beech Japanese white birch Japanese oak and so on

httpwwwenvgojpearthondankasantei_k18_02mat02_1pdf

Why do people love (like) forests

The forest environment has been enjoyed by humans for a long time because of

The quiet atmosphere

The beautiful scenery

The mild climate

The clean fresh air in the forest

What is a forest bathing trip (Shinrin-yoku)

A forest bathing trip is a short leisurely trip visiting a forest called Shinrinyoku in Japanese which is similar to a natural aromatherapy

The purpose of forest bathing trip is relaxation and recreation by breathing in volatile substances from trees called phytoncides such as alpha-pinene and limonene

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 2: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

What are natural environments(green spaces)

There are numerous definitions of natural environments (also called green spaces)

The Centres for Disease Control define them as ldquoopen undeveloped land with natural vegetationrdquo parks forests playing fields river corridors and the like

Nature is defined as bdquothe environment in which organisms or their biotopes expressly manifest themselves In addition to nature reserves this also includes farmland production forest urban green spaces and back gardens‟ (Health Council of the Netherlands 2004)

What is a forest

In 2000 the Forest Resources Assessment (FRA) 2000 project defined the ldquoforestrdquo as follows

Forest includes natural forests and forest plantations

It is used to refer to land with a tree canopy cover of more than 10 percent and area of more than 05 ha (hectare)

Forests are determined both by the presence of trees and the absence of other predominant land uses

The trees should be able to reach a minimum height of 5 m

httpwwwfaoorgDOCREP004Y1997Ey1997e1mhtm

What is a forest in Japan

In Japan forest is used to refer to land with a tree canopy cover of more than 30 percent and area of more than 03 ha (hectare)

The trees should be able to reach a minimum height of 5 m with a width of more than 20 m

The forests include Japanese cypress (Chamaecyparisobtuse Hinoki in Japanese) Japanese cedar (Cryptomeria Sugi in Japanese) Japanese beech Japanese white birch Japanese oak and so on

httpwwwenvgojpearthondankasantei_k18_02mat02_1pdf

Why do people love (like) forests

The forest environment has been enjoyed by humans for a long time because of

The quiet atmosphere

The beautiful scenery

The mild climate

The clean fresh air in the forest

What is a forest bathing trip (Shinrin-yoku)

A forest bathing trip is a short leisurely trip visiting a forest called Shinrinyoku in Japanese which is similar to a natural aromatherapy

The purpose of forest bathing trip is relaxation and recreation by breathing in volatile substances from trees called phytoncides such as alpha-pinene and limonene

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 3: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

What is a forest

In 2000 the Forest Resources Assessment (FRA) 2000 project defined the ldquoforestrdquo as follows

Forest includes natural forests and forest plantations

It is used to refer to land with a tree canopy cover of more than 10 percent and area of more than 05 ha (hectare)

Forests are determined both by the presence of trees and the absence of other predominant land uses

The trees should be able to reach a minimum height of 5 m

httpwwwfaoorgDOCREP004Y1997Ey1997e1mhtm

What is a forest in Japan

In Japan forest is used to refer to land with a tree canopy cover of more than 30 percent and area of more than 03 ha (hectare)

The trees should be able to reach a minimum height of 5 m with a width of more than 20 m

The forests include Japanese cypress (Chamaecyparisobtuse Hinoki in Japanese) Japanese cedar (Cryptomeria Sugi in Japanese) Japanese beech Japanese white birch Japanese oak and so on

httpwwwenvgojpearthondankasantei_k18_02mat02_1pdf

Why do people love (like) forests

The forest environment has been enjoyed by humans for a long time because of

The quiet atmosphere

The beautiful scenery

The mild climate

The clean fresh air in the forest

What is a forest bathing trip (Shinrin-yoku)

A forest bathing trip is a short leisurely trip visiting a forest called Shinrinyoku in Japanese which is similar to a natural aromatherapy

The purpose of forest bathing trip is relaxation and recreation by breathing in volatile substances from trees called phytoncides such as alpha-pinene and limonene

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 4: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

What is a forest in Japan

In Japan forest is used to refer to land with a tree canopy cover of more than 30 percent and area of more than 03 ha (hectare)

The trees should be able to reach a minimum height of 5 m with a width of more than 20 m

The forests include Japanese cypress (Chamaecyparisobtuse Hinoki in Japanese) Japanese cedar (Cryptomeria Sugi in Japanese) Japanese beech Japanese white birch Japanese oak and so on

httpwwwenvgojpearthondankasantei_k18_02mat02_1pdf

Why do people love (like) forests

The forest environment has been enjoyed by humans for a long time because of

The quiet atmosphere

The beautiful scenery

The mild climate

The clean fresh air in the forest

What is a forest bathing trip (Shinrin-yoku)

A forest bathing trip is a short leisurely trip visiting a forest called Shinrinyoku in Japanese which is similar to a natural aromatherapy

The purpose of forest bathing trip is relaxation and recreation by breathing in volatile substances from trees called phytoncides such as alpha-pinene and limonene

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 5: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Why do people love (like) forests

The forest environment has been enjoyed by humans for a long time because of

The quiet atmosphere

The beautiful scenery

The mild climate

The clean fresh air in the forest

What is a forest bathing trip (Shinrin-yoku)

A forest bathing trip is a short leisurely trip visiting a forest called Shinrinyoku in Japanese which is similar to a natural aromatherapy

The purpose of forest bathing trip is relaxation and recreation by breathing in volatile substances from trees called phytoncides such as alpha-pinene and limonene

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 6: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

What is a forest bathing trip (Shinrin-yoku)

A forest bathing trip is a short leisurely trip visiting a forest called Shinrinyoku in Japanese which is similar to a natural aromatherapy

The purpose of forest bathing trip is relaxation and recreation by breathing in volatile substances from trees called phytoncides such as alpha-pinene and limonene

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 7: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest bathing trips (Shinrin-yoku) in Japan

Incorporating forest bathing trips into a good lifestyle was first proposed in 1982 by the Forest Agency of Japan and the first kick off meeting was held at Akasawa in Nagano prefecture located in northwestern Japan

Now it has become a useful and popular relaxation and stress management activity in Japan

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 8: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest environment and Immune function

It is well known that immune system including natural killer (NK) cells plays an important role in defense against bacteria viruses and tumors

It is also well known that stress inhibits immune function

Forest environment may reduce stress

Therefore we speculate that forest environment may have beneficial effect on immune function by reducing stress

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 9: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Natural killer (NK)

Blood

darr

Red blood cells White blood cells platelet

darr

Granulocytes Lymphocytes Macrophages

darr

T cells NK cells B cells

(Immune cells)

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 10: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Relationship between incidence rate of cancer and NK activity

Kazue Imai et alLancet 2000 356 1795ndash99Subjects 3625Periods of follow-up11 years

People with lower NK activity

People with lower NK activity

People with higher NK activity

People with higher NK activity

Incid

ence

rare o

f Can

cer

Incid

ence

rare o

f Can

cer

Males

Females

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 11: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

NK

Granzymes Perforin Granulysin

Apoptosis

GrA

GrB

Gr3K

GrH

GrM

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of NK-induced apoptosis

(Tumor cell)

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 12: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Cancers and NK cellsCancer cells rarrCriminals

NK cellsrarrPolicemen

Policemen>>CriminalsrarrSafepeace

NK cells >>Cancers rarrHealth

Criminals>>Policemen rarrInsecurity

Cancer cells>>NK cellsrarrCancer

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 13: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Todayrsquos topics

1 Effect of 2-night3-day trips to forest parks on human immune function

2 Effect of a day trip to a forest park on human immune function

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 14: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Objective

To investigate the effect of the forest

environment on human immune function

We investigated NK (natural killer)

activity the numbers of NK cells and

intracellular levels of anti-cancer proteins

such as perforin granzyme and

granulysin in human lymphocytes during

visiting to forest fields

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 15: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Subjects and schedule

1 Subjects ① and ② 12 healthy male subjects aged 37-55 years (mean 431plusmn61) ③ 13 healthy female nurses aged 25-43 years (mean 288plusmn46)

2 Schedule Three-daytwo-night trips in the beginning of Sept at 3 different forest fields

3 On day 1 subjects departed to forest fields in the morning then walked for 25km during 2hs in the afternoon at a forest field

4 On day 2 subjects walked for 25km during 2hs in the morning and afternoon respectively at two different forest fields

5 On day 3 the subjects finished the trip and returned to Tokyo after blood was drawn and a questionnaire survey was completed

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 16: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Subjects were walking in a forest(Japanese oak Japanese white birch Bamboo grass)

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 17: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Japanese cypress

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 18: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Schedule for taking blood samples

Blood samples were taken at 800 am in all experiments

Working day Before the trip at 800 am

Day 2 of the trip at 800 am

Day 3 of the trip at 800 am

Day 7 after the trip at 800 am

Day 30 after the trip at 800 am

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 19: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Parameters

NK activity number of NK cells

Intracellular Perforin Granulysin Granzymes AampB

Estrogen progesterone in blood

Adrenaline and noradrenaline in urine (stress hormones)

POMS (Profile of Mood States)

Sleeping hours

Physical activity

Questionnaire for stress

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 20: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A forest visit significantly enhanceshuman NK activity in males

plt005 plt001 from before the trip plt005 from Day 1

Effect of a forest bath trip on human NK activity

0

10

20

30

40

Before Day 1 Day 2

NK

acti

vity

()

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 21: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest visits increased NK activity and this effect lasted for more than 7 days in both males and females

Male

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day30

NK

acti

vit

y (

)

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

35

Before Day 1 Day 2 Day 7 Day 30N

K a

cti

vit

y (

)

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 22: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A trip to a place without forest does notenhance human NK activity in malesEffect of a trip in a place without forest on NK activity

0

5

10

15

20

25

30

35

Before Day 1 Day 2

NK a

vtiv

ity (

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 23: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Question

Q Why do forest visits increase human NK activity

A1 The number of NK cells increaseduarr

A2 The intracellular anti-cancer proteins increaseduarr

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 24: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H100 101 102 103 104

FL2-H

Before the trip 1 day after trip 7 days after trip

6256 5161 4887 173201149

398039222827

NK cells

Tce

lls

Forest visit significantly increasedthe number of NK cells in males

Li et al J Biol Regul Homeost Agents 201024(2)157-65

In this subject the NK cells increased from 2827 to 3922 on day 1 and 3980 on day 7 after the trip

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 25: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest visit significantly increased the number of NK cells in males

plt001 significantly different from before the trip plt001 significantly

different from Day 1

0

200

400

600

800

1000

Before Day 1 Day 2

NK N

um

ber

ul

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 26: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest visits increased NK cells and this effect lasted for more than 7 days in both males and females

Male

0

100

200

300

400

500

600

Before Day 1 Day 2 Day 7 Day30

No

of

NK

cell

su

l

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

5

10

15

20

25

30

Before Day 1 Day 2 Day 7 Day 30N

K c

ells

()

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 27: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A forest visit significantly increased granulysin perforin granzyme AB-expressing lymphocytes

plt001 from before the trip $ plt001 from Day 1

0

200

400

600

800

1000

1200

1400

1600

1800

GRN Perforin GrA GrB

Num

ber

of c

ells

ul

Before

Day 1

Day 2

Li Q et al Int J Immunopathol Pharmacol 200720(2 Suppl 2)3-8

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 28: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest visits increased intracellular anti-cancer proteins and this effect lasted for more than 7 days in

both males and females

Male

0

10

20

30

40

50

60

70

Perforin GrA GrB GRN

Po

siti

ve r

ate(

Before

Day 1

Day 2

Day 7

Day30

plt005 plt001 from before the trip

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Female

0

10

20

30

40

50

60

Perforin GrA GrB GRN

Po

sit

ive r

ate

(

)

Before

Day 1

Day 2

Day 7

Day 30

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 29: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Factors affecting NK activity and the countermeasures

Circadian rhythm rarr Taking blood samples at the same time

Physical activity rarr Setting it at the same level

Alcohol drinking rarrAbstaining from drinking

(During the experiment)

Estrogen progesterone rarr Measuring it

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 30: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A forest visit decreased urinary adrenaline whereas a city tourist trip did not affect this

Forest bathing trip

0

1

2

3

4

5

6

Before Day 1 Day 2

plt005 from Before

ug

g

Cr

Li Q et al Int J Immunopathol Pharmacol 200821(1)117-27

City tourist trip

0

1

2

3

4

5

6

Before Day 1 Day 2

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 31: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A forest visit decreased urinary adrenaline and noradrenaline in

females

Urinary adrenaline

0

2

4

6

8

10

Before Day 1 Day 2

ug

g C

reati

nin

e

plt001 Li Q et al J Biol Regul Homeost Agents 200822(1)45-55

Urinary noradrenaline

0

20

40

60

80

100

Before Day 1 Day 2

ug

g C

reati

nin

e

68darr

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 32: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Forest bathing trips reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

POMS test Mean+SE (n=53)

0

10

20

30

40

50

60

Anxiety Depression Anger Vigour Fatigue Confusion

T S

core

s

Before After

plt001 significantly different from before Li Q et al Jpn J Hyg 63 (2) 412 2008

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 33: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Stress and immune response

StressorTension Anxiety

(Stress response)

Release of Stress hormones

Immune

functiondarr

Disturbance of autonomic nerves

ForestdarrReducing stressdarrRecover NK activity darrNK activity increased

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 34: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Question

It is not clear whether a day trip to a forest park also increases human NK activity

In the present study we addressed this question

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 35: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A day trip to a forest park

1 Subjects 12 healthy male subjects aged 34-53 years (mean 442plusmn60)

2 Schedule A day trip in the end of July to a forest park at Saitama prefecture located in the north of Tokyo Japan

3 The subjects walked for two hours each in the morning and afternoon for total of about 4 km in the forest park and then returned to Tokyo

4 A questionnaire of the Profile of Mood States (POMS) test was conducted before during and after the walking

5 Blood was sampled on the second day and on day 7 after the trip and 6 days prior to the trip as a control

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 36: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A day trip to a forest park

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 37: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A day trip to a forest park increases human natural killer (NK) activity and NK cells

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 38: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

100 101 102 103 104

FL1-H100 101 102 103 104

FL1-H

Before After

6064 44851849

858

2485

1645

T cells

Granzyme A

Effect of a day trip to a forest park on Granzyme A-expressing cells in lymphocytes

In this subject the total of Granzyme A-expressing cells increased from

2707 (1849+858) to 4130 (2485+1645) after the trip

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 39: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A day trip to a forest park increases the expression of anti-cancer proteins in lymphocytes

Perforin Granzyme A Granzyme B Granulysin

plt001

Li et al J Biol Regul Homeost Agents 201024(2)157-65

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 40: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

A day trip to a forest park reduces cortisol in serum

plt001 p=0053

Li et al J Biol Regul Homeost Agents 201024(2)157-65

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 41: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Concentration of volatile substances (phytoncides) in

the air of the forest park calculated as α-pinene (ngm3)

Kind of phytoncides

Quercus serrata

forest area

Pine forest

area

Isoprene 52916 98

Tricyclene 151 181

α-Pinene 700 2411

Camphene 124 203

β-Pinene 188 398

D-Limonene 109 222

Bornyl acetate 00 111

The concentration of phytoncides represents the mean concentrations of

each chemical between 930 am and 1530 pm with consecutive sampling

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 42: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

NK

Granzymes Perforin Granulysin

Apoptosis (cell death)rarrNK activity uarr

GrA

GrB

Ca++uarr K+darr

AIF Cyto-C

release

Mechanism of forest bathing-induced NK activity

(Tumor cell)

Forest bathing

Reduce Stress

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 43: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Conclusions

1 Forest visits significantly increase human NK activity in both males and females which was mediated by increases in the number of NK cells and the intracellular anti-cancer proteins

2 This effect lasted for more than 7 days even 30 days after the trips

rarrPreventive effect on cancers

3 Forest visits also significantly reduce the levels of urinary adrenaline and noradrenaline which are stress hormones

rarrStress management

4 Phytoncides from forests and relaxation may contribute to this effect

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 44: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Other effects

1 Forest visits significantly reduce blood pressure and blood glucose

rarrpreventive effects on hypertension diabetes and metabolic syndrome

2 Forest visits stabilize the activity of autonomic nerves by increasing the activity of parasympathetic nerves and decreasing the activity of sympathetic nerves

3 Forest visits reduce the scores of anxiety depression anger fatigue and confusion whereas increase the score of vigor

rarrpreventive effects on depression

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 45: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Fuji TV (News Speak) reported our research on forest medicine on

November 8 2005

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 46: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

The Japan Times reported our research on forest medicine on 200852

Friday May 2 2008

Forest therapy taking rootResearchers find that a simple stroll among trees has real benefits

By AKEMI NAKAMURAStaff writer

For stressed-out workers this may someday be a doctors prescription Walk around in the woods

httpsearchjapantimescojpcgi-binnn20080502f1html

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 47: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

An interview from Bloomberg TVJuly 1 2009

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 48: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

The New York TimesReported our research on forest medicine on July 5 2010

Environ Health Prev Med 20101527-37

Environ Health Prev Med 20101518-26

Int J Immunopathol Pharmacol 2007203-8

J Biol Regul Homeost Agents 20082245-55

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 49: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

ReallyThe Claim Exposure to Plants and Parks Can Boost Immunity

This time of year allergies and the promise of air-conditioning tend to drive people indoors

But for those who can take the heat and cope with the pollen spending more time in nature might have some surprising health benefits In a series of studies scientists found that when people swap their concrete confines for a few hours in more natural surroundings mdash forests parks and other places with plenty of trees mdash they experience increased immune function

Stress reduction is one factor But scientists also chalk it up to phytoncides the airborne chemicals that plants emit to protect them from rotting and insects and which also seem to benefit humans

One study published in January included data on 280 healthy people in Japan where visiting nature parks for therapeutic effect has become a popular practice called ldquoShinrin-yokurdquo or ldquoforest bathingrdquo On one day some people were instructed to walk through a forest or wooded area for a few hours while others walked through a city area On the second day they traded places The scientists found that being among plants produced ldquolower concentrations of cortisol lower pulse rate and lower blood pressurerdquo among other things

A number of other studies have shown that visiting parks and forests seems to raise levels of white blood cells including one in 2007 in which men who took two-hour walks in a forest over two days had a 50-percent spike in levels of natural killer cells And another found an increase in white blood cells that lasted a week in women exposed to phytoncides in forest air

THE BOTTOM LINE

According to studies exposure to plants and trees seems to benefit health

ANAHAD OrsquoCONNOR scitimesnytimescom

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 50: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

Int J Immunopathol Pharmacol 200720(2)3-8Forest bathing enhances human natural killer activity and

expression of anti-cancer proteinsLi Q Morimoto K Nakadai A Inagaki H Katsumata M Shimizu T Hirata Y Hirata K Suzuki H

Miyazaki Y Kagawa T Koyama Y Ohira T Takayama N Krensky AM Kawada T

Department of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

In order to explore the effect of forest bathing on human immune function we investigated natural killer (NK) activity the number of NK cells and perforin granzymes and granulysin-expression in peripheral blood lymphocytes (PBL) during a visit to forest fields Twelve healthy male subjects age 37-55 years were selected with informed consent from three large companies in Tokyo Japan The subjects experienced a three-daytwo-night trip in three different forest fields On the first day subjects walked for two hours in the afternoon in a forest field and on the second day they walked for two hours in the morning and afternoon respectively in two different forest fields Blood was sampled on the second and third days and NK activity proportions of NK T cells granulysin perforin and granzymes AB-expressing cells in PBL were measured Similar measurements were made before the trip on a normal working day as the control Almost all of the subjects (1112) showed higher NK activity after the trip (about 50 percent increased) compared with before There are significant differences both before and after the trip and between days 1 and 2 in NK activity The forest bathing trip also significantly increased the numbers of NK perforin granulysin and granzymes AB-expressing cells Taken together these findings indicate that a forest bathing trip can increase NK activity and that this effect at least partially mediated by increasing the number of NK cells and by the induction of intracellular anti-cancer proteins

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 51: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

J Biol Regul Homeost Agents 200822(1)45-55A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects

Li Q Morimoto K Kobayashi M Inagaki H Katsumata M Hirata Y Hirata K Shimizu T Li YJ Wakayama Y Kawada T Ohira T Takayama N Kagawa T Miyazaki YDepartment of Hygiene and Public Health Nippon Medical School Tokyo Japan

Abstract

We previously reported that forest bathing trips enhanced human NK activity number of NK cells and intracellular anti-cancer proteins in lymphocytes and that the increased NK activity lasted for more than 7 days after the trip in male subjects In the present study we investigated the effect of forest bathing trip on human NK activity in female subjects Thirteen healthy nurses age 25-43 years professional career 4-18 years were selected with informed consent The subjects experienced a three-daytwo-night trip to forest fields On day 1 the subjects walked for two hours in the afternoon in a forest field on day 2 they walked for two hours each in the morning and afternoon in two different forest fields and on day 3 the subjects finished the trip and returned to Tokyo after drawing blood and completing a questionnaire Blood and urine were sampled on the second and third days during the trip and on days 7 and 30 after the trip NK activity numbers of NK and T cells and granulysin perforin and granzymes AB-expressing lymphocytes in the blood samples the concentrations of estradiol and progesterone in serum and the concentrations of adrenaline and noradrenaline in urine were measured Similar control measurements were made before the trip on a normal working day The concentrations of phytoncides in the forests were measured The forest bathing trip significantly increased NK activity and the numbers of NK perforin granulysin and granzymes AB-expressing cells and significantly decreased the percentage of T cells and the concentrations of adrenaline and noradrenaline in urine The increased NK activity lasted for more than 7 days after the trip Phytoncides such as alpha-pinene and beta-pinene were detected in forest air These findings indicate that a forest bathing trip also increased NK activity number of NK cells and levels of intracellular anti-cancer proteins in female subjects and that this effect lasted at least 7 days after the trip Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]

Page 52: Qing Li, MD, PhD Nippon Medical School Tokyo, Japan · What is a forest? In 2000, the Forest Resources Assessment (FRA) 2000 project defined the “forest” as follows: Forest includes

References1 Li Q et al Phytoncides (wood essential oils) induce human natural killer cell activity

Immunopharmacol Immunotoxicol 28 (2) 319-33 2006

2 Li Q et al Forest bathing enhances human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 20 (S2) 3-8 2007

3 Li Q et al Visiting a forest but not a city increases human natural killer activity and expression of anti-cancer proteins Int J Immunopathol Pharmacol 200821(1)117-27

4 Li Q et al A forest bathing trip increases human natural killer activity and expression of anti-cancer proteins in female subjects J Biol Regul Homeost Agents 200822(1)45-55

5 Li Q et al Relationships between percentage of forest coverage and standardized mortality ratios (SMR) of cancers in all prefectures in Japan The Open Public Health Journal 2008 1 1-7

6 Li Q et al Effect of phytoncide from trees on human natural killer function Int J Immunopathol Pharmacol 200922(4)951-9

7 Li Q Effect of forest bathing trips on human immune function Environ Health Prev Med 201015(1)9-17

8 Li Q et al A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects J Biol Regul Homeost Agents 201024(2)157-65

9 Li Q and Kawada T Effect of forest environments on human natural killer (NK) activity Int J Immunopathol Pharmacol 2011 24 (S1) 39-44

10 Li Q et al Acute effects of walking in forest environments on cardiovascular and metabolic parameters Eur J Appl Physiol 2011 Mar 23 [Epub ahead of print]