Food as medicine: evidence from studies with carrots and ...€¦ · Effect of beta-carotene on...

Food as medicine: evidence

from studies with carrots and

rosehips

Kirsten Brandt

Food Quality & Health Research Group

Human Nutrition Research Centre

Newcastle University

Identification of bioactive

compounds in food plants

Overview of food and human nutrition

research at Newcastle University

Anti-cancer compound in carrots

Anti-arthritis compound in rosehips

Human Nutrition Research

Centre

Food Quality

Molecular

Nutrition

Public Health

Nutrition

• Understanding links between food, nutrition and health

• From molecules to populations

• Testing efficacy of dietary interventions

• Strongly multi-disciplinary: Comprises 11 principal investigators

from five groups in four institutes/schools from two faculties

http://www.ncl.ac.uk/hnrc/

Specific

health issues

esp. obesity

Mechanisms

using

genomic

technologies

Novel diet-

related

biomarkers

Specific

foods and

dietary

patterns

Food Quality

Molecular

Nutrition

Public Health

Nutrition


Centre

http://www.ncl.ac.uk/hnrc/

Examples of ongoing and upcoming intervention trials with food and food supplements.

Ongoing:

‘VegBP’: Effects of different types of vegetables on blood pressure, funded by FSA.

‘Provide’: Test of food supplement, target group older people, commercially funded.

Upcoming:

Test of alginates on fat uptake, funded by BBSRC.

Two commercial trials under negotiation.


Centre

Why we know so little about

medicinal compounds in plant foods

Almost all food and health research has been focused on avoiding harmful extremes, either deficiencies or toxic effects.

Other effects have rarely been investigated.

So for almost all food components we don’t know if a modest increase or decrease will be good or badfor health.

This knowledge is an absolute requirement for any improvements of food in terms of benefits for health.

Assessing plant foods from a

pharmacological perspective

Minimum requirement for a health-promoting

compound: A physiological effect on human

tissue must be likely.

Estimated by:

Physiological effect = concentration in food *intake of food * bioavailability of compound *bioactivity (= effect on cells) of compound at

the physiological concentration.

If any factor is near 0, the product is near 0!

Example: functional compounds in carrot

Carrot intake is strongly correlated with

reduced risk of cancer

Alpha-carotene is better correlated with

reduced risk of cancer than beta-carotene

(which also occurs in other foods than

carrots)

Neither alpha- nor beta-carotene have

appreciable effect in vitro at physiological

concentrations

Anti-cancer compounds in carrots

Effect of beta-carotene on lung cancer risk

80

100

120

140

<1.09 1.09-

1.70

1.71-

2.70

>2.70

Intake from diet (mg/day)

Nu

mb

er

of

ca

ses

Supplement(20 mg/day)

Placebo

Each data point represents 3380

male smokers for 6 year

Carrots provide 60-80% of the

beta-carotene in Northern

European diets and are the

single most important source

Data from Albanes et al. 1996


Effect of beta-carotene on lung cancer risk

80

100

120

140

<1.09 1.09-

1.70

1.71-

2.70

>2.70

Intake from diet (mg/day)

Nu

mb

er

of

ca

ses

Supplement(20 mg/day)

Placebo

Each data point represents 3380

male smokers for 6 years

The lack of interaction shows

that the benefit of diets high in

beta-carotene is due to a

confounding factor, such as

another compound in carrots

Data from Albanes et al. 1996


Carrots are the major dietary

source of the polyacetylene

falcarinol

Falcarinol from ginseng has

been indicated as a possible

anti-cancer compound

Falcarinol is a natural pesticide

with strong biological activity

Pure falcarinol is toxic


0

0.2

0.4

0.6

0.8

1

1.2

1.4

0.1 1 10 100 1000 10000

Dose-response of in vitro effects of falcarinol and -caroteneProliferation of primary mammary epithelial cells in collagen gel cultures.

Mitogen

ic r

esponse

(rela

tive t

o b

asal m

ediu

m)

BM

Falcarinol, -carotene (ng ml-1)

Brandt et al. 2004


Bioavailability of falcarinol

Brandt et al. 2004


Effect of carrots and falcarinol on Azoxy-

methane induced colorectal cancer in rats

0

20

40

60

80

100

120

Small

ACF (1-3)

Me dium

ACF (4-6)

Large

ACF (>6)

Tumours

(³ 1 mm)

Type and size of lesion

Number of (pre)neoplastic le sions in % of control treatment

Carrot

Falcarinol

Concentrations

corresponding to

normal food

Kobaek-Larsen et al. 2005


So what are the next steps?

Several studies have confirmed the in vitro data in

different cell types.

We are presently starting another cancer prevention

study with mice.

We have also done several studies of the effect of

cooking on the content of falcarinol.

If the effect is confirmed in humans and the content

in the diet increased:

There will be huge benefits for society (consumer health).

The market for carrots and carrot-derived products will

increase.


Erik Hansen, roses and rosehips

Anti-arthritis compounds in rosehips

Dog rose

(Rosa canina)

On a scale from 0 (no impact) to 4 (almost total relief of pain) after 4 months of treatment with standardized

rose-hip powder (SRHP) or placebo.


From: Warholm et al.,

Current Therapeutic

Research

64: 21-31, 2003

Percentage of patients (47 per group) experiencing reduction in joint pain after 3

weeks of treatment.


From: Winther et al.,

Scandinavian Journal

of Rheumatology

34: 302–308, 2005

Also noted 50%

reduction in

consumption of

paracetamol (in all

studies)


From: Larsen et al.,

J. Natural Products

66: 994-995, 2003

(figure adapted from

Christensen et al.,

Grøn Viden 155,

2003)

1 Kg dried ground rosehips (R. canina)

Successive extraction

(i) Hexane (ii) Dichloromethane (iii) Methanol (iv) Water

Fractionation (column chromatography)

F1 F10 F11 F20F12

F12 (10-12)F11 (10-12)F10 (10-12) F14 (10-12)

Anti-inflammatory galactolipid (DOTGG) (250 mg, purity > 98%)

= anti-inflammatory activity, = no activity

Fractionation (preparative HPLC)

F1 (10-12)

(2S)-1,2-Di-O-[(9Z,12Z,15Z)-octadeca-9,12,15-trienoyl]-3-O--D-galactopyranosyl glycerol)


DOTGG

O

CH2

CH

H2C

OH

OH

HO

CH2OH

O

O

O

O

CH3

CH3

O


0

20

40

60

80

100

DMSO 0,1 1 10 50 100

Inh

ibit

ion

of

chem

ota

xis

of

PM

K

leu

kocy

tes

(%)

8277

6264

70

Concentration of DOTGG (mg/ml)

Cultivation and harvest of rosehips.

Variety ‘Lito’, selected for yield and quality


Analysis of DOTGG for standardisation


Retention time (min)

706050403020100

200

150

100

50

0

-75

UV detection at 203 nm

mA

U

DOTGG


Present status1. Rosehip product marketed as food supplement,

under the trade name LitoZin

2. The company’s turnover more than quadrupled since

publication of the research

3. Health claim used: ‘May play a valuable role in the

care of joints and joint tissues’

4. A stronger health claim requires development into a

drug, or demonstration of effect in healthy volunteers

5. This is not considered cost-effective by the company

6. The only losers are the patients

Translated from the

report ‘Socio-

economic value of

selected research

projects at Danish

Institute of

Agricultural

Sciences’, Kvistgaard

Consult, 2003.

Based on a saving of

Dkr 6000 (approx.

£600) per patient per

year if used by 50%

of arthritis patients.


Thank you for your

attention!

Any questions?

Food as medicine: evidence from studies with carrots and ...€¦ · Effect of beta-carotene on...

Documents

Transcript of Food as medicine: evidence from studies with carrots and ...€¦ · Effect of beta-carotene on...