Chicory fibre, the root of digestive healthd3hip0cp28w2tg.cloudfront.net/uploads/2016-12/...Figure...

Chicory fibre, the root of digestive health

Hélène Alexiou

Senior Manager Nutrition Communication

BENEO Institute

© 2016 BENEO

Natural solutions are top of mind to look after

digestive health

Q: What do you currently do to look after your digestive health?

n (UK) = 1099 | Filter: None

“High fibre diet;

plenty of fresh

fruit/vegetables.”

“Eat a balanced

diet with plenty

of fruit and

vegetables.”

“I eat

healthily

and

exercise

regularly.”

Q: Given the answer options below, what do you currently do to

look after your digestive health?


Looking after digestive

health

TOP 5

% of

consumers

Drinking more water 58%

Eating fibre-rich foods 57%

Eating fruit 51%

Exercising 45%

Eating wholegrain

foods

41%

Source: BENEO’s digestive health research, 2015

© 2016 BENEO

Q: To what extent do you agree with the following motives for you to eat or drink digestive health products?


Top 2 Drivers

5 – Completely agree 4 3 2 1 – Completely disagree

69%

66%

66%

66%

63%

62%

60%

58%

58%

53%

45%

27%

25%

24%

25%

24%

22%

22%

21%

22%

19%

16%

42%

41%

41%

40%

39%

40%

38%

37%

36%

34%

29%

28%

29%

30%

30%

31%

32%

34%

35%

35%

38%

42%

2%

3%

2%

3%

4%

4%

4%

4%

5%

7%

8%

2%

2%

3%

2%

2%

3%

3%

2%

3%

3%

5%

Is good for my overall health

Helps me keep my digestive system regular

Helps me feel healthy

Makes me feel better

Is good for my intestinal health

Helps me feel less bloated

Promotes good bacteria in the digestive system

Helps me improve my body’s natural defences

Relieves me from constipation

Contributes to a lowered risk of colorectal cancer

Can help me lose weight

Motives for eating or drinking digestive health

products

Source: BENEO’s digestive health research, 2015

© 2016 BENEO

The dietary fibre gap: Europe (females/males)

4 Literature search by BENEO Institute (2011); updated Aug 2016

Fra

nc

e

Be

lgiu

m

De

nm

ark

Sw

ed

en

Fin

lan

d

No

rwa

y

Th

e N

eth

erl

an

ds

Ge

rma

ny

Au

str

ia

Ita

ly

UK

Sp

ain

Po

rtu

ga

l

Ire

lan

d

-20

-15

-10

-5

0

5

Delta between dietary fibre intake and recommendation in g/day

females

males

© 2016 BENEO

Europe: prevalence of constipation

5

Spain: 4.1%1

France: 14 - 22.4%1

United

Kingdom:

7.7%1

Norway: 13.8%2

(Rome II criteria)

Germany:

14.9%1

Italy: 7.95%1

Greece: 13.8%3

Russia: 16.5%2

1: self-reported

2: according to Rome criteria II

3: according to Rome criteria III

Schmidt, de Gouveia Santos (2014) 41 (1): 70-76 Enck et al (2016) UEG J 4(3): 429-437

Wald et al (2008):Aliment Pharmacol Ther 28: 917-930

Lazebnik et al (2011) Ekep Clin Gastroenterol 3: 68-73

© 2016 BENEO

Inulin from chicory has a positive effect on bowel

function

6

Meta-analysis of 5 intervention studies (N=252):

• Showing significant effects of inulin on bowel motor function, including:

stool frequency

stool consistency

transit time

Supportive for a beneficial effect of inulin on bowel function!

Collado Yurrita et al. Nutr Hosp. 2014 Aug 1;30(2):244-52.

© 2016 BENEO

Chicory root fibres:

Inulin & Oligofructose

Chicory roots

(15-17% inulin)

© 2016 BENEO

Fermentation in the large intestine

Prebiotic fermentation

Increase in bacterial

metabolites

Increase in break down

products of chicory root

f iber fermentation:

Short chain fatty acids

(SCFA*)

Increase in bulk

Bacteria

Bacteria

Non-absorbed nutrients

from small intestine

Inulin/

Oligo-

fructose

SCFA

H2

CO2

Partial re-absorption

of water

Bloodstream Feces/Excretion

*SCFA = Short-Chain Fatty Acids (acetate, propionate, butyrate)

CH4

© 2016 BENEO

A complex orchestra that is positively influenced

by chicory root fibers

not digestible in small intestine

water binding capacity

softer stools

bacterial fermentation in large intestine

bacteria

bowel content

fecal bulk

intestinal transit time

bowel movement frequency

gas production

SCFA production

water content of digesta/feces

chemical stimulation of peristaltic reflex

9

Physiological mechanism fully

accepted by EFSA.

The prebiotic fermentation of chicory

inulin plays a key role!

© 2016 BENEO

Art. 13(5) EU dossier on inulin and normal bowel

function: human studies

10

0 20 40 60 80 100

Isakov et al (2013) - 3 g/d

Bouhnik et al (2007) - 5 g/d

Kolida et al (2007) - 5 g/d

Brighenti et al (1999) - 9 g/d

Schulz et al (2012) - 12 g/d

Grasten et al (2003) - 13 g/d

Den Hond et al (2000) - 15 g/d

Kleessen et al (2007) - 15 g/d

Gibson et al (1995) - 15 g/d



Stool frequency increase, chicory inulin vs. placebo/control (%)

*

*

Improvement

* Proprietary & confidential study

EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2015. Scientific Opinion on the substantiation of a health claim

related to “native chicory inulin” and maintenance of normal defecation by increasing stool frequency pursuant to Article 13(5) of Regulation (EC)

No 1924/2006. EFSA Journal 2015;13(1):3951, 12 pp. doi:10.2903/j.efsa.2015.395

© 2016 BENEO

Art. 13(5) - Orafti®inulin & normal bowel function

Commission Regulation (EU) 2015/2314

11 Ref. Commission Regulation (EU) 2015/2314 of 7 December 2015 authorising a health claim made on foods, other than those referring to the reduction of disease risk

and to children's development and health and amending Regulation (EU) No 432/2012; available at:

http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32015R2314&rid=1








© 2016 BENEO

Orafti®Inulin improves bowel function by more

frequent bowel movements

12

Randomised, PC, DB,cross-over design

Bowel movement frequency after a 4 week ingestion of 12 g/d (3x4 g)

Orafti®Inulin compared to maltodextrin

Consumption of 12 g/d

Orafti®Inulin led to a

significantly higher

frequency of bowel

movements compared

to maltodextrin

p = 0.038

*

0

1

2

3

4

5

Maltodextrin Orafti® Inulin

Bo

we

l m

ove

me

nts

/we

ek

Maltodextrin

Orafti® Inulin

Micka et al (2016) Int J Food Sci Nutr 5:1-8. [Epub ahead of print]

© 2016 BENEO

Gastrointestinal comfort

• Assessed with a GI symptoms diary (5-point scale):

• 0 = not at all, 1 = very slightly, 2 = slightly, 3 = moderately, 4 = extremely

• Straining • lower with inulin (“not at all”) vs. maltodextrin (“very slightly” to “not at all”)

• Feeling of incomplete emptying • Comparably low with median 1.0 for inulin and 1.3 for maltodextr. (“very slightly”)

• Abdominal discomfort • Similar in both periods rated as “not at all”

• Bloating/distension • No stat. signif. difference: 0.9 for maltodextrin and 1.1 for inulin (“very slightly”)

• Passage of gas • “very slightly” to “slightly” range (1.1-1.9)

Micka et al (2016) Int J Food Sci Nutr 5:1-8. [Epub ahead of print]

© 2016 BENEO

PAC-QOL - Health related QoL questionnaire

specific for constipated subjects

• PAC-QOL (Patient-Assessment of Constipation Quality of Life)

• a validated instrument to assess QoL in patients suffering from constipation.

• Selected validated test blocks: physical discomfort and satisfaction dimension

• The lower the score, the better rated is the quality of life

• Satisfaction improved during inulin vs. maltodextrin (p=0.059) intake

14 Micka et al (2016) Int J Food Sci Nutr 5:1-8. [Epub ahead of print]

© 2016 BENEO

Inulin in patients with gastrointestinal

hypersensitivity

Azpiroz et al. (2016) J Clin Gastroenterol [Epub ahead of print].

https://www.ncbi.nlm.nih.gov/pubmed/27680592 , accessed October 06, 2016. 15

Study design

• Placebo-controlled, parallel, randomized, double-blind study

• 36 Subjects with abdominal symptoms and reduced tolerance of intestinal gas

• Inulin (2 x 4 g/day, in liquid, at breakfast and dinner) vs maltodextrin (2 x 4 g/d)

• 4 weeks intervention

• Gas challenge test

https://www.ncbi.nlm.nih.gov/pubmed/27680592


© 2016 BENEO

Gas test: gas retention & perception

16

Significantly reduced gas retention

with inulin

p = 0.035

0

100

200

300

400

500

600

700

800

Baseline End Baseline End

Ga

s r

eta

ine

d (

ml)

Placebo Inulin

0

1

2

3

4

5

6

15 30 45 60 75 90 105 120 135 150 165 180

Pe

rce

pti

on

(s

co

re)

Time (min)

Placebo Baseline

Placebo End

Inulin Baseline

Inulin End


https://www.ncbi.nlm.nih.gov/pubmed/27680592 , accessed October 06, 2016.

Both inulin and placebo significantly

reduced perception score to a similar extent



© 2016 BENEO

Results: gastrointestinal symptoms

17

0

2

4

6

8

10


Sc

ore

Flatulence

Placebo Inulin

0

1

2

3

4

5

6

7

8

9

10


Sc

ore

Borborygmi

Placebo Inulin

0

2

4

6

8

10


Sc

ore

Discomfort/pain

Placebo Inulin

-5

-4

-3

-2

-1

0

1

2

3

4

5

Baseline End Baseline EndSc

ore

Digestive well-being

Placebo Inulin

0

2

4

6

8

10


Sc

ore

Bloating

Placebo Inulin

CONCLUSION

GI symptoms are in the medium range (in both groups) as expected in hypersensitive

subjects, with no differences between groups

Results are in line with perception data during gas test: no GI stress with inulin





© 2016 BENEO

Conclusion from the publication



18

“In this context, our study indicates that a daily dose of inulin, which

promotes the proliferation of bifidobacteria, is well tolerated by

hypersensitive subjects with gastrointestinal complaints and may have

favourable effects on gut function. Hence, the current study would favor

the use of inulin over restrictive dietary advice such as FODMAPs

restriction to treat functional gastrointestinal symptoms, at least in

patients with normal bowel habits or constipation. “

Prof F. Azpiroz et al.


© 2016 BENEO

What are prebiotics?

“A dietary prebiotic is a selectively fermented ingredient that results in specific changes in the

composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon

host health.”

- International Scientific Association for Probiotics and Prebiotics (ISAPP), Nov 2008, London, Ontario -

Characteristics of prebiotics (Gibson et al., 2004):

• Resistance to hydrolysis and absorption

• Fermented by intestinal microflora

• Selective stimulation of growth and/or activity of intestinal bacteria ( bifidobacteria, lactobacilli)

associated with health and disease

Confirmed prebiotics (ISAPP 2008, Gibson et al., 2010) :

• Inulin-type Fructans

(Orafti® inulin, oligofructose, Synergy1)

• Galactans

• Lactulose

HO O

HO OH

OH

O HO

OH

O HO

O HO

OH

O

O HO

OH OH

O

n

inulin

oligofructose

© 2016 BENEO

Bifidobacteria increase: marker for prebiotic

benefits of chicory root fibers

0

2

4

6

8

10

12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

10lo

g f

ae

ca

l b

ifid

ob

ac

teri

a c

ou

nts

pe

r m

l

Individual studies*

Significant bifidobacteria increase with inulin and/or oligofructose in adults

20

control/

baseline/

placebo

inulin/

oligofructose

*List of references is available upon request

© 2016 BENEO

Related health outcomes of chicory root fibers are

seen along two mechanistic routes...

21

Selective proliferation of beneficial bacteria,

mainly bifidobacteria and lactobacilli

Stimulation of beneficial microbial activities

Figure modified from Crittenden 2006; Source: Windows to Science 1/2012: Prof. RA Rastall: Healthy Human gut microbiota

– Specific perspectives. Presented at 2nd European BENEO Scientific Symposium, 12-13 March 2012,

© 2016 BENEO

Stable-isotope method

Figure: Eef Boets (KU Leuven), Gut day 2014, Posterpresentation

Boets et al (2015) Nutrients 7: 8916-8929 22

Production of SCFA

during bacterial

fermentation of inulin in

the colon

SCFA are transported

through the portal vein

into liver

Constant infusion with

labeled SCFA results in

enrichment of labeled SCFA

in plasma

Colonic fermentation whole- body

SCFA lowering labeled SCFA

enrichment and increased SCFA

turnover

Increase of SCFA

turnover represents the

part of SCFA produced in

the colon

© 2016 BENEO

Amounts and proportions produced in vivo after

consumption of inulin

23

Quantification of the colonic production of SCFA in healthy humans after

inulin intake using a stable-isotope dilution method.

Estimated colonic production within 12 h was:

• Acetate: 137 mmol (82%)

• Propionate: 11 mmol (6%)

• Butyrate: 20 mmol (12%)

Boets et al (2015) Nutrients 7: 8916-8929

Inulin is basically fermented to

acetate > butyrate > propionate

Results confirm earlier in vitro studies

Unique study using a stable-isotope diluation

method

© 2016 BENEO

24 Roberfroid et al, Br J Nutr 2010, 104 (Suppl 2)

Main physiological targets for prebiotic effects -

From immunity to weight management…

Increase in mineral absorption

and improvement of bone health

(bone Ca content, BMD)

Improvement of intestinal functions

(stool regularity, bulking, consistency)

Improvement and/or stabilization

of gut microbiota composition

Modulation of GI peptide

production, energy metabolism

and satiety

Reduction of risk of obesity,

T2DM, Metabolic Syndrome

Improvement of intestinal barrier functions,

reduction of metabolic endotoxemia

Reduction of risk of

intestinal infections

Initiation and modulation

of immune response

Health benefits and

main physiological

targets for

prebiotic effects

© 2016 BENEO

Additional outreach of prebiotic fermentation of

chicory root fibers

25

• Increase in calcium absorption to support bone strength • Change in true calcium absorption

at 8-week and at 1-year intervention1:

• Cholesterol-lowering effect • Inclusion criteria of meta-analysis2:

• Randomized control trial

• Mean TC, LDL-c, HDL-c, TG concentration

• Products enriched with inulin only

• Conclusion: Based on this meta-analysis, it can be stated that oral inulin has beneficial

effects on total cholesterol and LDL-c, as well as triglyceride concentration in the

plasma of hyperlipidemic subjects, and has no effects on plasma lipids in

normolipidemic subjects.

1 Abrams et al. (2005) Am J Clin Nutr 82(2):471-476. 2 Guo et al. (2012) Clin. Lipidol. 7(2):215-222.

* P < 0.001

** P = 0.04

© 2016 BENEO

Recent systematic reviews & meta-analyses for

prebiotics and inulin-type fructans

• Preventive use of prebiotics decreases the rate of

infections in infants and children (Lohner et al. 2014)

• Prebiotics consumption associated with

improvements in satiety and reductions in

postprandial glucose and insulin (Kellow et al. 2014)

• Inulin has beneficial effects on total cholesterol

and LDL-C as well as triglycerides in

hyperlipidemic subjects (Guo et al. 2012)

• Prebiotics reduce total cholesterol and LDL-C in

adult subjects with overweight and obesity;

Prebiotics reduce triglyceride and increase HDL-C

levels in diabetics (Beserra et al. 2014)

• Inulin-type fructans may have benefits for LDL-C

reduction (all study populations), improvements

shown for HDL-C and glucose control in

T2DM (Liu et al. 2016)

© 2016 BENEO

Subjective Appetite Ratings

Satiety Regulation (Hormones)

Energy Intake

Body Weight / Composition

I can

measure it

Satiety, energy intake & body weight

I can

sense it

It works:

It makes me eat

less!

It has an effect on

me and my body!

Chicory root

fibres reduce

the caloric

intake!

© 2016 BENEO

From the colon to other organs of the body: The

reach-out of the microbiota …

Brain

Lung breath

Kidney urine

Blood

Liver

Neurotransmitter

Serotonin Cytokines

Bacterial metabolites

SCFA, others

GLP-1, PYY,..

microbiota

Large

intestine

Immune cells Nervous system Hormonal system

28

© 2016 BENEO

Animal study with Orafti®Synergy1: Importance of acetate

derived from colonic fermentation for effects on appetite

• Orafti® Synergy1 results in reduced energy intake and lower body weight gain

• Peripheral acetate infusions reduce energy intake suggests acetate as an anorectic signal

• Acetate derived from colonic fermentation is taken up by the brain, preferentially accumulates in the hypothalamus and impacts hypothalamic metabolism Change in anorectic / orexigenic neuropeptide expression favoring reduction in appetite and body weight

• Neuronal activity pattern in the brain stimulated by acetate infusions is identical to that observed upon inulin feeding

Acetate might play central role for chicory root fiber effects on energy intake and body weight

29 Frost et al. (2014) Nature Commun5:3611.

© 2016 BENEO

Chicory root fibres reduce energy intake

8 g/d

Orafti®Synergy1

Orafti®P95

Other OF

Inulin

1)

*

*

**

*

*

*

**

1)

*

*

*

*

1) Data not reported in % energy intake change * p < 0.05 ** p < 0.01

Patterned bars represent supportive evidence from

self-reported data or discontinuous fibre intake.

Version: 11 Nov 2015

1

2

30

Consistent evidence from

several human

intervention studies for

normal weight, overweight

and obese adults and

children

© 2016 BENEO

Chicory root fibres

Supporting gut health and beyond…

Type of key studies Demonstrated physiological properties

Mouth Not fermented

Small Intestine Patients with ileostomy Not digested/absorbed

Glycemic response

Insulin response

When replacing sugars/available carbohydrates

When replacing sugars/available carbohydrates

Large Intestine Prebiotic Selective stimulation of mutualistic microbiota (bifidobacteria )

Fully fermentable Beneficial saccharolytic fermentation , proteolytic fermentation

-> Short chain fatty acids , pH

Bowel function Improved bowel motor function, stool frequency

Mineral absorption Calcium absorption

Bone mineral density

Gastrointestinal tolerance

Subjective perception of the increased gut activity might be

noticeable at high intakes, but generally not disturbing

Metabolism Weight management Energy intake

Weight , influence on satiety, fat mass

Inner resistance Incidence of infectious diseases

Attenuation of glycaemia /

insulinaemia – long term

Glycated haemoglobin (HbA1c) and fructosamine , insulin

resistance (HOMA)

Calorie Reduction / Fibre enrichment

Sugar or fat replacement

When replacing starch, sugar or fat calories (caloric value

2 kcal/g)

31

© 2016 BENEO

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32

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