Chicory fibre, the root of digestive health. Hélène Alexiou Senior Manager Nutrition Communication BENEO Institute

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1 Chicory fibre, the root of digestive health Hélène Alexiou Senior Manager Nutrition Communication BENEO Institute

2 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 Q: Given the answer options below, what do you currently do to look after your digestive health? n (UK) = 1099 Filter: None Looking after digestive health TOP 5 % of consumers Drinking more water 58% Eating fibre-rich foods 57% Eating fruit 51% High fibre diet; plenty of fresh fruit/vegetables. Eat a balanced diet with plenty of fruit and vegetables. I eat healthily and exercise regularly. Exercising 45% Eating wholegrain foods 41% Source: BENEO s digestive health research, 2015

3 Motives for eating or drinking digestive health products Q: To what extent do you agree with the following motives for you to eat or drink digestive health products? n (UK) = 1099 Filter: None Drivers Top 2 Is good for my overall health 27% 42% 28% 2% 69% Helps me keep my digestive system regular 25% 41% 29% 3% 2% 66% Helps me feel healthy 24% 41% 30% 2% 3% 66% Makes me feel better 25% 40% 30% 3% 2% 66% Is good for my intestinal health 24% 39% 31% 4% 2% 63% Helps me feel less bloated 22% 40% 32% 4% 3% 62% Promotes good bacteria in the digestive system 22% 38% 34% 4% 3% 60% Helps me improve my body s natural defences 21% 37% 35% 4% 2% 58% Relieves me from constipation 22% 36% 35% 5% 3% 58% Contributes to a lowered risk of colorectal cancer 19% 34% 38% 7% 3% 53% Can help me lose weight 16% 29% 42% 8% 5% 45% 5 Completely agree Completely disagree Source: BENEO s digestive health research, 2015

4 France Belgium Denmark Sweden Finland Norway The Netherlands Germany Austria Italy UK Spain Portugal Ireland The dietary fibre gap: Europe (females/males) females males Delta between dietary fibre intake and recommendation in g/day Literature search by BENEO Institute (2011); updated Aug

5 Europe: prevalence of constipation Norway: 13.8% 2 (Rome II criteria) United Kingdom: 7.7% 1 Germany: 14.9% 1 Russia: 16.5% 2 France: % 1 Greece: 13.8% 3 Spain: 4.1% 1 Italy: 7.95% 1 1: self-reported 2: according to Rome criteria II 3: according to Rome criteria III Schmidt, de Gouveia Santos (2014) 41 (1): Enck et al (2016) UEG J 4(3): Wald et al (2008):Aliment Pharmacol Ther 28: Lazebnik et al (2011) Ekep Clin Gastroenterol 3:

6 Inulin from chicory has a positive effect on bowel function 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 Aug 1;30(2):

7 Chicory root fibres: Inulin & Oligofructose Chicory roots (15-17% inulin)

8 Fermentation in the large intestine Non-absorbed nutrients from small intestine Bacteria Prebiotic fermentation Increase in bulk Bacteria Inulin/ Oligofructose Partial re-absorption of water Increase in bacterial metabolites Increase in break down products of chicory root fiber fermentation: Short chain fatty acids (SCFA*) SCFA CH 4 CO 2 H 2 Bloodstream Feces/Excretion *SCFA = Short-Chain Fatty Acids (acetate, propionate, butyrate)

9 A complex orchestra that is positively influenced by chicory root fibers water binding capacity not digestible in small intestine bacterial fermentation in large intestine water content of digesta/feces bacteria gas production SCFA production softer stools bowel content fecal bulk intestinal transit time Physiological mechanism fully accepted by EFSA. The prebiotic fermentation of chicory chemical stimulation of peristaltic reflex inulin plays a key role! bowel movement frequency 9

10 Art. 13(5) EU dossier on inulin and normal bowel function: human studies Kleessen et al (1997) - 40 g/d Kleessen et al (1997) - 20 g/d Gibson et al (1995) - 15 g/d Kleessen et al (2007) - 15 g/d Den Hond et al (2000) - 15 g/d Grasten et al (2003) - 13 g/d Schulz et al (2012) - 12 g/d Brighenti et al (1999) - 9 g/d Kolida et al (2007) - 5 g/d Bouhnik et al (2007) - 5 g/d Isakov et al (2013) - 3 g/d Improvement Stool frequency increase, chicory inulin vs. placebo/control (%) * * Proprietary & confidential study * EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 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: /j.efsa

11 Art. 13(5) - Orafti inulin & normal bowel function Commission Regulation (EU) 2015/2314 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: 11

12 Orafti Inulin improves bowel function by more frequent bowel movements Bowel movements/week 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 p = * Maltodextrin Orafti Inulin Consumption of 12 g/d Orafti Inulin led to a significantly higher frequency of bowel movements compared to maltodextrin 0 Maltodextrin Orafti Inulin Micka et al (2016) Int J Food Sci Nutr 5:1-8. [Epub ahead of print] 12

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

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

15 Inulin in patients with gastrointestinal hypersensitivity 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 Azpiroz et al. (2016) J Clin Gastroenterol [Epub ahead of print]. accessed October 06,

16 Perception (score) Gas retained (ml) Gas test: gas retention & perception 800 p = Baseline End Baseline End Placebo Inulin Significantly reduced gas retention with inulin Placebo Baseline Placebo End Inulin Baseline Inulin End Time (min) Both inulin and placebo significantly reduced perception score to a similar extent Azpiroz et al. (2016) J Clin Gastroenterol [Epub ahead of print]. accessed October 06,

17 Score Score Score Score Score Results: gastrointestinal symptoms Borborygmi Baseline End Baseline End Placebo Inulin Flatulence Baseline End Baseline End Placebo Inulin Discomfort/pain Baseline End Baseline End Placebo Inulin CONCLUSION Bloating Digestive well-being 4 0 Baseline End Baseline End 2-1 subjects, with no differences between -2groups 0 Baseline End Baseline End -3 Results are in line with perception data during gas test: no GI stress with inulin Placebo Inulin -4 Placebo Inulin -5 GI symptoms are in the medium range (in both groups) as expected in hypersensitive Azpiroz et al. (2016) J Clin Gastroenterol [Epub ahead of print]. accessed October 06,

18 Conclusion from the publication 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. Azpiroz et al. (2016) J Clin Gastroenterol [Epub ahead of print]. accessed October 06,

19 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 OH Confirmed prebiotics (ISAPP 2008, Gibson et al., 2010) : Inulin-type Fructans (Orafti inulin, oligofructose, Synergy1) Galactans Lactulose HO HO HO inulin OH O OH O O HO O OH O HO O n O HO OH OH oligofructose

20 Bifidobacteria increase: marker for prebiotic benefits of chicory root fibers Significant bifidobacteria increase with inulin and/or oligofructose in adults log faecal bifidobacteria counts per ml *List of references is available upon request Individual studies* control/ baseline/ placebo inulin/ oligofructose 20

21 Related health outcomes of chicory root fibers are seen along two mechanistic routes... 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, March 2012, 21

22 Stable-isotope method Production of SCFA during bacterial fermentation of inulin in the colon Colonic fermentation whole- body SCFA lowering labeled SCFA enrichment and increased SCFA turnover SCFA are transported through the portal vein into liver Constant infusion with labeled SCFA results in enrichment of labeled SCFA in plasma Increase of SCFA turnover represents the part of SCFA produced in the colon Figure: Eef Boets (KU Leuven), Gut day 2014, Posterpresentation Boets et al (2015) Nutrients 7:

23 Amounts and proportions produced in vivo after consumption of inulin 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%) Inulin is basically fermented to acetate > butyrate > propionate Results confirm earlier in vitro studies Unique study using a stable-isotope diluation method Boets et al (2015) Nutrients 7:

24 Main physiological targets for prebiotic effects - From immunity to weight management Improvement of intestinal functions (stool regularity, bulking, consistency) Improvement and/or stabilization of gut microbiota composition Increase in mineral absorption and improvement of bone health (bone Ca content, BMD) Modulation of GI peptide production, energy metabolism and satiety Health benefits and main physiological targets for prebiotic effects Initiation and modulation of immune response Reduction of risk of obesity, T2DM, Metabolic Syndrome Reduction of risk of intestinal infections Improvement of intestinal barrier functions, reduction of metabolic endotoxemia Roberfroid et al, Br J Nutr 2010, 104 (Suppl 2) 24

25 Additional outreach of prebiotic fermentation of chicory root fibers Increase in calcium absorption to support bone strength Change in true calcium absorption at 8-week and at 1-year intervention 1 : * P < ** P = 0.04 Cholesterol-lowering effect Inclusion criteria of meta-analysis 2 : 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): Guo et al. (2012) Clin. Lipidol. 7(2):

26 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)

27 Satiety, energy intake & body weight It works: It makes me eat less! It has an effect on me and my body! I can measure it I can sense it Subjective Appetite Ratings Satiety Regulation (Hormones) Body Weight / Composition Energy Intake Chicory root fibres reduce the caloric intake!

28 From the colon to other organs of the body: The reach-out of the microbiota Brain Lung breath Neurotransmitter Serotonin Nervous system Cytokines Immune cells Kidney Blood GLP-1, PYY,.. Liver Hormonal system urine Large intestine microbiota Bacterial metabolites SCFA, others 28

29 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 Frost et al. (2014) Nature Commun5:

30 Chicory root fibres reduce energy intake Orafti Synergy1 Orafti P95 * Other OF Inulin * * ** 1) 1) * ** * * * * * 8 g/d Consistent evidence from several human intervention studies for normal weight, overweight and obese adults and children 1 2 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

31 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 Bowel function Mineral absorption Gastrointestinal tolerance Beneficial saccharolytic fermentation, proteolytic fermentation -> Short chain fatty acids, ph Improved bowel motor function, stool frequency Calcium absorption Bone mineral density 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 Calorie Reduction / Fibre enrichment Sugar or fat replacement Glycated haemoglobin (HbA1c) and fructosamine, insulin resistance (HOMA) When replacing starch, sugar or fat calories (caloric value 2 kcal/g) 31

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