FODMAPS

1. FODMAPS CLINICAL USE AND EFFICIACY IN IBS ALICIA LUSARDI NICOLE TEKKORA FEBRUARY 28, 2016

2. What is IBS? • Chronic GI disorder1,2 • Description: Stomach distension, abdominal discomfort, and irregular bowel movements without disturbance to the lining of the GI tract1,2 • Irregular bowel movements can include diarrhea, constipation, or a combination of the two1 • Categorized as: IBS-D, IBS-C, IBS-M, or IBS-U1,6 • IBS-D= most common (40-60% cases)6 • Gold-standard diagnosis: Rome III (symptom-based specifications) along with elimination of any organic disorder1 • Most prevalent GI condition encountered by medical professionals1 • Up to half of patients seen by gastroenterologists have IBS1 1

3. What is IBS? • Worldwide: 10-20% occurrence1 • Mainly women between 30-50 yrs1 • Affects 20% of young children3 • High medical expense1 • Associated with low quality of life1 • Close to 2/3 IBS patients find symptoms to correspond with their diet1 • Foods that worsen symptoms: Carbs not 100% absorbed, foods with high lipid content, caffeine, alcohol, spicy foods1 2

4. Gold Standard: Rome III Criteria1 3

5. What causes IBS?1 4 • Cause is ? • Current research speculates: • Increased responsiveness to pain or excessive responsiveness to pain in intestines • Excessive bacterial proliferation in small intestine • Minor visceral inflammation • Stress and/or depression6 • Not well understood, multiple facets likely contribute to disorder

6. Pathophysiology6 5 • Inflammation: • Higher probability of developing IBS after GI infection • Higher numbers of mucosal inflammatory signals • Greater amounts of certain inflammatory mediators (i.e. IL-6 and IL-8) in the blood • High levels of mucosal mast cells in the colon, which are essential for fighting against pathogens and could directly affect enteric sensory nerves • Amplified communication between GI tract and CNS • Caused by changes in GI tract within the lumen, bloating, and chemical changes • Changes in CNS • Irregular afferent processing and stimulation of brain areas controlling emotions and arousal • Anxiety and depression • Lack of control regarding communication between gut bacteria and the CNS

7. How do we treat IBS?1 • Principal aim: decrease symptoms • Hard to treat because of the wide array of symptoms, difficult to accurately assess effectiveness of treatments, and high placebo effect seen in studies4 • Pharmacological approach: • Bulking agents • Anticholinergics • Antispasmodics • Antidiarrheals • Antidepressants • Not effective without combining with lifestyle changes • Lifestyle modifications: • DIET • Physical activity • CBT • Hypnosis 6

8. Diet Treatments1 FODMAP diet Gluten free diet Probiotics supplementation Fiber supplementation Elimination diets 7

9. WHAT ARE FODMAPS? 1 FODMAP stands for “Fermentable Oligosaccharide, Disaccharide, Monosaccharide, Polyols” 8 1

10. What is the FODMAP Diet? 9 Represents a class of carbs that are not completely absorbed in the small intestine  H2 and CH4 fermented by bacteria in the small/large intestine, causing bloat and discomfort1,2 Discharge fluid into the small intestine, causing bloat and higher amount of water entering the large intestine1 Includes lactose, fructose, fructans, galacto-oligosaccharides, and polyols or sugar alcohols1 More commonly encountered in past 30 yrs due to increase in concentrated fruit juices and wide implementation of high fructose corn syrup in food/drink products5 Research proposes that FODMAPs heighten endothelial barrier permeability  immune response and inflammation4

11. What is the FODMAP Diet? Studies have shown that FODMAPs increase digestion time and sensory afferent signals from the enteric system 6 On average, IBS patients consume 15-30 g/d; diet recommends lowering intake to 5-18g/d6 75% IBS patients see improvement by following low FODMAP diet4 Key: Adherence!4 Long-term effects of diet implementation have yet to be studied4 Possible issue: FODMAPs increase healthy gut microbiota so lack of consumption may lead to negative alterations in the composition of species4 10

12. LIST OF HIGH FODMAPS 11

13. Literature Review1 • Nanayakkara et al., 2016: Review article (13 studies) • 6 RCTs, 7 - mix of retrospective, prospective uncontrolled studies • Small study sizes (< 100 participants) • Females ages 35 to 50 • Primary outcome measure = changes in GI symptoms (global and individual) • Variety of scoring scales • Food frequency questionnaires, food diaries • Dietary advice given by specialized RD in most studies 12

14. Literature Review1 13 • Nanayakkaraet al., 2016 • Results - low FODMAP diets associated with:

15. Literature Review cont.7 14 • Marsh et al., 2015: Meta-analysis (22 studies) • 6 RCT, 16 non-randomized (NR) • Pooled Odds Ratio and 95% CI calculated for FODMAP effect on: • Symptom Severity Score (SSS) –validated 1997 • measure of abdominal pain, frequency of pain, bloating, bowel habit dissatisfaction, interference with quality of life • 100 point Visual Analogue Scale (VAS) • IBS Quality of Life (QOL) score – validated 1998 • 41 descriptive quality of life items – 5 point Likert response scale

16. Literature Review cont.7 15 • Marsh et al., 2015 • Results – Low FODMAP diets associated with:

17. Literature Review cont.7 Marsh et al., 2015 16

18. Literature Review cont.8 17 • Halmos et al., 2014: RCT, single blind cross over • 30 IBS, 9 healthy • 21 days on low FODMAP or typical Australian diet • Food provided on low FODMAP diet • Washout period of 21 days between arms • Symptoms evaluated using 0-100mm Visual Analogue Scale • Adherence measured through diet record and breath test • Addressed confounding by providing all intervention diets that were matched for nutrients except for FODMAP content

19. Literature Review cont.8 • Halmoset al., 2014 18

20. Literature Review cont.9 19 • Shepard et al., 2008: double blind, RCT • Placebo controlled, re-challenge trial • 26 patients with IBS or FM, previously responded to FODMAP diet (22 weeks) • 2 week period, given 1 of 4 test substances, graded dose • Fructans • Fructose • Fructans/ Fructose mix • Glucose • 4 arms, 14 day washout period between each • Instructed to continue on low FODMAP diet

21. Literature Review cont.9 20 • Shepard et al., 2008 • Primary end point “were your symptoms adequately controlled at the end of this phase?” • Secondary end points, mean VAS scores on individual symptoms at highest dose

22. Literature Review cont.9 • Shepard et al., 2008 • Potential issues: liquid vs. solid form, blinding on liquids may have been compromised due to taste • Greatest for fructose and fructans suggesting 2 FODMAPs may be additive • Small number completed all arms at highest dose reducing statistical power 21

23. Literature Review cont.6 • Staudacher et al., 2012: RCT • 41 patients with bloating and diarrhea • IBS Rome III criteria (constipation excluded) • Intervention group – No FODMAPs • Control group – Regular Diet • 7 day baseline evaluation consisting of food diary, stool consistency and validated symptom scale • Each group contacted weekly by RD • Final week patients completed 7 day symptom, stool and food diary 22

24. Literature Review cont.6 Staudacher et al., 2012: RCT 23

25. Literature Review cont.6 24 Staudacheret al., 2012: RCT

26. Literature Review cont.6 25 • Staudacheret al., 2012: RCT • Paradox- FODMAPS reduces bifidobacteriaBUT…. Bifidobacteria associated with: • Reduced abdominal pain in healthy and IBS • Therapeutic effects in IBS • Long term studies needed • Supplementation with probiotics? • Restriction of fermentable short-chain carbohydrates is an effective management strategy for IBS, resulting in reductions inoverallsymptoms and bloating

27. Literature Review cont.10 • Böhn et al., 2015: RCT, single-blind, parallel • 75 patients • 38 assigned to FODMAP • 37 to diet normally prescribed for IBS (regular meal pattern; avoid large meals; and reduced intake of fat, insoluble fibers, caffeine, and gas producing foods – beans, cabbage, and onions) • Symptoms assessed with Symptom Severity Scale (SSS) • 4 weeks • 4 day food diary before and after intervention • Adherence assessed through food diaries 26

28. Literature Review cont.10 Böhnet al., 2015 27

29. Common Shortcomings • Small sample sizes • Methodological issues with blinding, contribute to bias, 40% • Long term effects unknown- studies needed • Altered microbiota? • Nutrient deficiencies? 28

30. Conclusion1 IBS is estimated to effect 10 to 15% globally 2/3 of patients associate symptoms with changes in diet Accounts for 50% of GI visits Associated with high medical costs 29

31. Conclusion1,7 • Pharmacological agents not effective alone • Other dietary interventions not shown to be effective: • Elimination diets (wheat, diary, caffeine) have not shown clinically significant effects • High Fiber diets • Probiotics – issues around strain, dose, inconclusive • Low FODMAP diets shown to be effective in reducing IBS symptoms 30

32. References Nanayakkara WS, Skidmore PM, O’Brien L, Wilkinson TJ, Gearry RB. Efficacy of the low FODMAP diet for treating irritable bowel syndrome: The evidence to date. Clinical and Experimental Gastroenterology. 2016. p. 131–42. Pedersen N, Vegh Z, Burisch J, Jensen L, Ankersen DV, Felding M, Andersen NN, Munkholm P. Ehealth monitoring in irritable bowel syndrome patients treated with low fermentable oligo-, di-, mono-saccharides and polyols diet. World Journal of Gastroenterology 2014;20:6680-4. Chumpitazi BP, Cope JL, Hollister EB, Tsai CM, McMeans AR, Luna RA, Versalovic J, Shulman RJ. Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome. Aliment PharmacolTher 2015;42:418-27. Maagaard L, Ankersen DV, Vegh Z, Burisch J, Jensen L, Pedersen N, Munkholm P. Follow-up of patients with functional bowel symptoms treated with a low FODMAP diet. World Journal of Gastroenterology 2016;22:4009-19. Wong WM. Restriction of FODMAP in the management of bloating in irritable bowel syndrome. Singapore Med J 2016;57:476-84. 31

33. References 32 Staudacher HM, Whelan K. Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: probiotics, prebiotics and the low FODMAP diet. ProcNutrSoc 2016;75:306-18. Marsh A, Eslick EM, Eslick GD. Does a diet low in FODMAPs reduce symptoms associated with functional gastrointestinal disorders? A comprehensive systematic review and meta-analysis. Eur J Nutr. 2016;55:897–906. Halmos EP, Power V a, Shepherd SJ, Gibson PR, Muir JG. A Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel&nbsp;Syndrome. Ygast [Internet]. Elsevier, Inc; 2014;146:67–75.e5. Available from: http://dx.doi.org/10.1053/j.gastro.2013.09.046%5Cnpapers2://publication/doi/10.1053/j.gastro.2013.09.046 SHEPHERD S, PARKER F, MUIR J, GIBSON P. Dietary Triggers of Abdominal Symptoms in Patients With Irritable Bowel Syndrome: Randomized Placebo-Controlled Evidence. ClinGastroenterolHepatol [Internet]. 2008;6:765–71. Available from: http://www.sciencedirect.com/science/article/pii/S1542356508001511 Böhn L, Störsrud S, Liljebo T, Collin L, Lindfors P, Törnblom H, Simrén M. Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome as Well as Traditional Dietary Advice: A Randomized Controlled Trial. Gastroenterology. 2015;149:1399–1407.e2.