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IBS and the Low FODMAP Diet Najwa El-Nachef, MD NCSGNA Conference September 20, 2014 Irritable Bowel Syndrome Affects up to 20% of adults in US Common symptoms include abdominal pain, bloating, constipation and/or diarrhea More frequent among females Associated with significant decrease in quality of life Major economic burden on patients, healthcare systems and community Remains poorly understood Horwitz et al. N Engl J Med 2001;344:1846-50 Mechanism of IBS Motility Visceral Hypersensitivity Central Processing Genetic Factors Psychological factors Inflammation Gut Microflora Dietary Factors Lea et al. Gastroenterol Clin North Am 2005;34:247-55 Treatment for IBS Focus on reduction of symptoms Pharmaceuticals Psychological therapy Fiber Probiotics/Antibiotics Dietary and Lifestyle Interventions Diet and IBS Relationship between diet and abdominal symptoms is well recognized From the patient’s perspective, the most frequently perceived cause for symptoms is food intolerance Up to 50% of patient’s with IBS symptoms worsen after a meal 60% of patients with IBS believe they have a food allergy Lea et al. Gastroenterol Clin North Am 2005;34:247-55 Diet and IBS Dairy Free Low fat High Fiber No coffee/alcohol Food diary, self-eliminate Gluten free diet Fermentable Carbohydrates Dietary carbohydrates can be classified into sugars, oligosaccharides and polysaccharides based on their degree of polymerisation. “Fermentable” owing to their availability for fermentation in the colon, which is either due to the absence or reduced concentration of suitable hydrolase enzymes for digestion or in the case of monosaccharides because of incomplete absorption in the small intestine. Low FODMAP Diet Ingested FODMAPs are poorly absorbed in the small bowel Small, osmotically active molecules which draw water into the large intestine FODMAPs are also fermented by colonic microflora, producing hydrogen and/or methane gas The increase in fluid and gas leads to diarrhea, bloating, flatulence, abdominal pain, and distension Low FODMAP Diet F: Fermentable O: Oligo- saccharides D: Di-saccharides M: Mono-saccharides A: and P: Polyols Fructose Simple monosaccharide Found naturally in many fruits. Also a constituent of sucrose and fructans. Normally absorbed in small intestine by two mechanisms: GLUT-5 transporter- present throughout small intesine. GLUT-2 transporter- requires equal amounts of glucose for more effective absorption. Failure to completely absorb free fructose leads to its delivery in the colon. Colonic bacteria rapidly ferment free fructose to hydrogen, carbon dioxide and short-chain fatty acids. Fructans Major source of fermentable carbohydrates Minimal digestion due to absence of enzymes in the human GI tract to digest the fructosylfructose glycosidic bonds Wheat and onion are major sources Commercial fructans dervied from sucrose or chicory root are increasingly added to prepared foods due to their textural and sensory properties Galacto-oligosaccharides Humans lack a-galactosidase enzymes, leading to the availability of GOD for colonic fermentation Milk, legumes and some grains, nuts and seeds Polyols Sugar Alcohol Absorbed in small intestine by passive diffusion Present in fruits and vegetables Commonly used in artificial sweeteners (sorbitol, mannitol, xylitol) Large amounts can cause osmotic diarrhea Foods to eliminate Fructans and galactans: wheat and rye in large amounts, onions, garlic, inulin, legumes, lentils, artichoke, soy milk and almond milk Lactose: milk, yogurt, ice cream, soft cheese Excess fructose: high fructose corn syrup, honey, agave, and various fruits (such as apple, pear and watermelon) Polyols: stones fruits (peach, plum, cherry), mushroom, cauliflower and sorbitol/mannitol Permissible Foods Grains: rice, oats, gluten free pasta, some gluten free breads and cereals Fruits: berries (except blackberries), citrus, banana, grapes, honeydew or cantaloupe melon, kiwifruit Vegetables: Carrots, corn, eggplant, zucchini, peppers, green beans, lettuce, cucumber, potato, and tomato are a few. Meats: All meats; avoid processed meats that contain ingredients like high fructose corn syrup, milk solids, or onion/garlic powder Milk: Lactose free milk, rice milk, lactose free yogurt, hard or ripened cheeses like cheddar and feta What is the data? Studies of the mechanisms underlying the effects of fermentable carbohydrates on gastrointestinal symptoms Delivery of Water/Fermentable Substrate Ileostomy volunteers Two diets tested for 4 days each. One high in FODMAPs and one low in FODMAPs All food prepared by investigators At baseline and on day 4, 24 hours effluent collected 10 patients, ileostomy because of IBD, no active disease Barrett et al. Aliment Pharmacol Ther 2010 Apr;31(8):874-82 Main effluent weight significantly less during LFD Subjects perceived significantly thicker consistency on LFD Barrett et al. Aliment Pharmacol Ther 2010 Apr;31(8):874-82 MRI Data with and without FODMAPs Murray et al. Am J Gastroenterol 2014;109:110-9 MRI Data Cont’d Studies investigating effectiveness on IBS symptoms Shepherd 2008 Double blinded, randomized placebocontrolled rechallenge trial 25 patients responded to dietary change Patients were randomly challenged by graded dose introduction of fructose, fructans or glucose taken as drinks 70-80% developed symptoms when rechallenged Shepherd. Clin Gastroenterol Hepatol 2008; 6: 765–71. Positive Global Symptoms Shepherd Clin Gastroenterol Hepatol 2008;6:765-771 Results for Overall Symptoms Fructan v. Fructose Mix Overall Pain Bloating Wind Nausea Tirednes s 0.4589 0.0103 0.0005 0.1986 0.0974 0.0016 0.1907 0.0405 0.0005 0.0640 0.0385 0.0003 0.8476 0.5727 0.2467 0.8838 0.4217 0.0148 0.0020 0.0010 0.0078 0.0176 0.0028 0.0046 0.0003 0.0611 0.2539 0.3065 0.7651 0.3312 0.0020 0.0002 0.0003 0.0002 0.1265 0.3328 Gluocse Fructose v. Mix Glucose Mix v. Glucose Low FODMAP Diet v. Standard Dietary Advice Symptom Group Improved % P value Bloating Standard FODMAP 49 82 0.002 Abdominal pain Standard FODMAP 61 85 0.023 Flatulence Standard FODMAP 50 87 0.001 Nausea Standard FODMAP 29 67 0.04 Composite score Standard FODMAP 49 86 <0.001 Staudacher J Hum Nutr Diet 2011;5:487-95 Halmos 2014 Crossover trial, 30 patients with IBS and 8 healthy individuals Randomly assigned to groups that received 21 days either of diet low in FODMAPs or a typical Australian diet Washout period 21 day before crossing over to the alternate diet. Almost all food was provided during the interventional diet periods All stools were collected from days 17-21 and assessed for frequency, weight, water content Halmos et al. Gastroenterology 2014;146:67–75 “I don’t know what the heck gluten is either but I’m avoiding it- just to be safe.” Is Gluten the Key Player? Supplementary Figure 1 Recruitment pathway and reasons for screen failure. Recruitment survey was a 23-item questionnaire about symptoms, diet, and investigations for celiac disease described previously.<ce:cross-ref refid="bib20" id="crosref0245"> 20 </c... Figure 2 Change in symptom severity from run-in for each dietary treatment over 7-day study period. Data shown represent mean ± SEM. Differences across the treatment arms were compared by Friedman test, in which overall symptoms ( P = .001), bloating ( P ... Biesiekiersk Gastroenterology, Volume 145, Issue 2, 2013, 320 - 328.e3 i Is FODMAP Accepted by Patients? FODMAP Popularity 668,000 results on Google 16,000“Likes” Several Many on Facebook Apps available complain too restrictive Summary FODMAPs Delivery do not cause IBS of dietary FODMAP to the distal small and proximal large intestine is a normal phenomenon, one that will generate symptoms if the underlying bowel response is exaggerated or abnormal. Summary Limited data, which are mainly composed of studies with relatively small sample sizes, support IBS symptom improvement with a lowFODMAP diet. Beneficial effect of a low FODMAP diet does not appear to be predominantly based on gluten avoidance No definite biomarkers as of now that are associated with symptom response Thank you!