Food Sensitivities and IBS

8/1/2013 Food Sensitivities and IBS Laura E. Matarese PhD, RD, LDN, CNSC, FADA, FASPEN Associate Professor Division of Gastroenterology, Hepatology, and Nutrition Brody School of Medicine and Department of Nutrition Science East Carolina University Greenville, NC October 20, 2013 DISCLOSURES Laura E. Matarese PhD, RD, LDN, CNSC, FADA, FASPEN Advisory Board NPSP Speaker s Bureau Abbott Nutrition OBJECTIVES Evaluate the role of food sensitivities and intolerances in the pathophysiology of IBS Identify foods that can provoke IBS symptoms Discuss the elimination diet in the management of IBS What s The Difference? Food Allergy an adverse immune response to the proteins in a food; may occur as the result of a humoral response (immunoglobulin E [IgE] antibody), a cellular response (i.e. T cells), or both Food Intolerance/sensitivity not a true food allergy: could be enzyme deficiency (e.g. lactase deficiency), chemical reactions, aversion. May also refer to IgG mediated reactions or other immune reactions to food. Food Allergy vs. Food Sensitivity Food Allergy vs. Food Sensitivity Food Allergy Type I Hypersensitivity IgE mediated Immediate, rapid onset Systemic, potentially life threatening Shared Symptoms: Nausea, vomiting, diarrhea, abdominal pain Different symptoms: Hives, tingling or itching in the mouth, swelling of the lips, face, tongue and throat, SOB, wheezing, nasal congestion, anaphylaxis Food Sensitivity Type III hypersensitivity IgG mediated Gradual, delayed response Localized, generally limited to the GI tract Shared Symptoms: Nausea, vomiting, diarrhea, abdominal pain Different symptoms: Gas, cramps, bloating, heartburn, headaches, irritability, nervousness Common Food Allergies: Dairy Eggs Wheat Soy Peanuts and tree Nuts Fish Chicken Corn Common Food Sensitivities: Dairy Wheat Peanuts Tree Nuts Lack G. NEJM.2008;359:1252 1

8/1/2013 Food: The Forgotten Factor in the Irritable Bowel Syndrome Studies of Elimination Diets Many of the therapeutic options commonly used for IBS have proved unsatisfactory. In a subset of patients, diet seems to play a role in the development of symptoms. Food can affect GI function and sensation > 60% of IBS patients associate symptoms with eating a meal 28% within 15 minutes 93% within 3 hours Food allergy or intolerance Gastro-colonic response Microbiome/Fermentation Gas Handling Psychological Factors Eswaran S, Tack J & Chey W. Gastroenterol Clin N Am 40 (2011) 141 162 Simren et al. Clin Gastro Hepatol 2007;5:201 Evidence that elimination diets based on IgG and IgE food antibodies have shown benefit in IBS Alterations of food antigen-specific serum IgG & IgE antibodies in patients with IBS, FD Food Elimination Based on IgG Antibodies in IBS: A Randomized Controlled Trial IBS pts had higher titers of IgG Type III hypersensitivity (Intolerance) Zuo et al. Clinical and Experimental Allergy, 37, 823 830, 2007 37 IBS, 28 functional dyspepsia, 20 controls No significant differences between IBS, FD and controls in the serum total IgE antibody titers Type I hypersensitivity (Allergy) Level A P<0.001 Atkinson, W et al. Gut 2004;53:1459-1464 150 patients tested for food specific IgG Randomized to IgG excluded foods (true diet) or sham After 6 weeks, 10% reduction in symptoms (p=0.024) After 12 weeks, 26% reduction (p<0.001) Symptoms improve with higher adherence Food-specific IgG 4 antibody-guided exclusion diet improves symptoms and rectal compliance in IBS Treating IBS with a Food Elimination Diet Followed by Food Challenge and Probiotics Zar et al. Scandinavian J Gastro 2005; 40: 800 Measured serum IgG 4 antibody titers to 16 common foods; foods excluded based on antibodies At 3 months and 6 months significant improvement in pain severity (p<0.001, p=0.005) pain frequency (p=0.034, p=0.027) bloating severity (p=0.001, p=0.024) satisfaction with bowel habits (p=0.004, p=0.016) the effect of IBS on life in general (p=0.008, p=0.002) Open label, n=20 Food specific IgG testing performed Food sensitivities addressed Significant reduction in # stools/day and pain scale (p<0.05) after 1 year Improved quality of life Drisko et al J Amer College of Nutrition, 2006. Vol. 25, No. 6, 514 522 2

% Patients With Lactose Intolerance 8/1/2013 Do carbohydrates produce symptoms in IBS? Very Low CHO Diet for IBS Dairy SD SD VLC VLC 15 females, mean age 46 yrs, BMI 32 Dietary interventions: 2 wks standard (55% CHO, 30% Fat, 15% Protein) 4 wks VLC (4% CHO, 51% Fat, 45% Protein) Responder rate: 100% Improvements in stool frequency p<0.001),consistency (p<0.001), pain (p<0.001), QoL (p=0.02) Mean weight loss of 3.1 kg Grains Fruits and Vegetables Austin et al. Clin Gastro Hepatol 2009;7:706 Prevalence of Lactose Intolerance in IBS 38% 26% IBS patients (n=251) Controls (n=174) ACG IBS Task Force Am J Gastro 2009; 104 (suppl 1); S1-S135 Prevalence and Presentation of Lactose Intolerance and Effects on Dairy Product Intake in Healthy Subjects and Patients With Irritable Bowel Syndrome P=0.008 P=0.004 P=0.03 Yang J. et al. Clin Gastro & Hepatology 2013;11:262 D-IBS n=60; controls n=60 hydrogen breath tests (HBT) to detect lactose malabsorption (LM) and lactose intolerance (LI) after double blind administration of 10, 20, and 40 g lactose in random order 7 14 days apart Prevalence of LM and LI increased with lactose dose; no difference between IBS and controls in LM prevalence at any dose Prevalence of LI was lower for controls than for D-IBS at all doses. Prevalence and Presentation of Lactose Intolerance and Effects on Dairy Product Intake in Healthy Subjects and Patients With Irritable Bowel Syndrome Number and severity of symptoms (TSS) P<0.05 P<0.01 D-IBS reported a greater number and severity of symptoms than controls at the 20-g dose The risk of LI is related to the dose of lactose ingested and intestinal gas production LI is increased in patients with D- IBS Self-reported LI, but not objective results from HBT, was associated with avoidance of dairy products Gluten Free Is it: a fad no benefit expected? a factor for IBS symptom relief? Celiac Disease chronic immune-mediated disease; life threatening? Sales of gluten free products have more than doubled since 2005 Euromonitor International forecasts: 2011 = $1.31 billion US, $2.67 billion globally 2015 = $1.68 billion US, $3.38 billion globally Yang J. et al. Clin Gastro & Hepatology 2013;11:262 3

% Normalization in Symptom Score 8/1/2013 A Spectrum of Disease With Overlap? Prevalence of Celiac Disease in IBS IBS Gluten Sensitivity Celiac Disease Case-controlled study Prospective Trial Motility/Visceral Sensation Brain-Gut Interactions Immune activation Altered Gut Microbiome Altered Permeability Motility/Visceral Sensation Brain-Gut Interactions Immune activation Altered Gut Microbiome Altered Permeability Non-Celiac Gluten Sensitivity Celiac Disease Mild gluten sensitivity Gluten hypersensitivity Gluten Intolerance Allergic Rx Adapted from Verdu EF, et al. Am J Gastroenterol 2009;104:1587-94. CD antibody (ttga and EMA) positive no biopsy; physician Dx Biopsy Proven Celiac disease prevalence 1% among IBS patients in US Saito-Loftus Y, et al. Am J Gastro 2008; 103(suppl 1):S472 Cash BD et al. Gastroenterol 2011;141:1187 Symptom Normalization in IBS-D After a Gluten Free Diet + ATB P=0.05 - ATB N=41 _ IBS-D patients stratified according to Celiac Disease associated antibodies Evaluation of normalization of abdominal symptoms & stool frequency after gluten free diet Serum antibodies can predict responders to gluten free diet IBS patients received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. AGA - anti-gliadin antibodies TTG - anti tissue-transglutaminase antibodies DQ2 - expression of the HLA-DQ2 Wahnschaffe et al. Clin Gastro Hept 2007;5:844 Biesiekierski JR et al. Am J Gastro 2011 106 (3)508-514. Gluten Induces Symptoms in IBS uncontrolled symptoms 13/19 (68%) gluten 6/15 (40%) placebo (P=0.0001) patients were significantly worse with gluten within 1 week overall symptoms (P=0.047) pain (P=0.016) bloating (P=0.031) satisfaction with stool consistency (P=0.024) tiredness (P=0.001) Biesiekierski JR et al. Am J Gastro 2011 106 (3)508-514. Non-Celiac Wheat Sensitivity in IBS: A Distinct Clinical Condition IBS pts N=920 IBS patients N=276 gluten sensitivity but non-celiac 2 weeks on wheat-containing diet and 2 weeks on placebo Changes in symptom severity over baseline during DBPC wheat challenge Carroccio A. et al. Am J Gastroenterol 2012; 107:1898 1906 4

8/1/2013 Histological Evidence Significant eosinophil infiltration of the duodenal and colon mucosa in wheat sensitive patients Of the total study group (N=920) 1/3 IBS pts had wheat sensitivity Carroccio A. et al. Am J Gastroenterol 2012; 107:1898 1906 Spectrum of gluten sensitivity & IBS Absence of celiac disease, gluten is a trigger for IBS in sensitive individuals Interaction of host genotype, diet, and intestinal microbiota? Reduction in bacterial fermentation Am J Gastro March 2011 Fructose and Fructans As Dietary Triggers for IBS symptoms Low FODMAP vs. Standard Diet for IBS p 0.002 vs. glucose DBPC - 25 IBS pts with fructose malabsorption who improved with a FODMAP + diet 4 way randomly assigned crossover challenge NICE: UK National Institute for Health and Clinical Excellence Guidelines Healthy eating guidelines 2 weeks of each diet with 10 d washout N=82 39 NICE Diet 43 low FODMAP Diet +Fermentable oligo-, di-, monosaccharides and polyols term coined by Shepherd et al Shepherd S et al, Clin Gastro Hepatol 2008;6:765 Staudacher HM, et al. J Hum Nutr Diet 2011 Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome Ong DK et al.j Gastroentero Hepatol 2010;25:1366 15 IBS; 15 controls 2 day consumption of high (50g/d) or low (9 g/d) FODMAP diet Higher levels of breath hydrogen produced with high FODMAP diet GI symptoms and lethargy induced by high FODMAP diet in IBS but not control Fermentable oligo-, di-, monosaccharides and polyols Fermentable Carbohydrate Restriction Reduces Luminal Bifidobacteria and Gastrointestinal Symptoms in Patients with Irritable Bowel Syndrome Staudacher HM et al. J. Nutr. 142: 1510 1518, 2012. Baseline fecal bifidobacteria concentration in IBS patients compared with change in bifidobacteria concentration after 4 wk of fermentable CHO restriction 5

Proportion of patients showing improvement (%) 8/1/2013 Fermentable Carbohydrate Restriction Reduces Luminal Bifidobacteria and Gastrointestinal Symptoms in Patients with Irritable Bowel Syndrome 90 80 70 60 50 40 30 20 10 0 p<0.05 Bloating Borborygmy Urgency Overall Symptoms Improvement of mean daily symptom score after 4 wk of habitual diet (control) or fermentable CHO restriction (intervention) Staudacher HM et al. J. Nutr. 142: 1510 1518, 2012. control intervention Let medicine be thy food and let food be thy medicine Hippocrates PRACTICE APPLICATIONS Although many IBS patients complain of symptoms after eating, true food allergies are uncommon Lactose intolerance may be more common in IBS Gluten sensitivity is a heterogeneous group of disorders that is much more common than Celiac Disease and likely causes IBS symptoms Short-chain CHO (FODMAPs) can trigger symptoms in IBS Further Reading Leung J and Crowe SE. Food Allergy and Food Intolerance. IN: Gastrointestinal and Liver Disease Desk Reference. Mullin GE, Matarese LE and Palmer M (eds). CRC Press 2012 Gibson PR. Food intolerance in functional bowel disorders. J Gastroenterol Hepatol. 26 Suppl 3:128-31, 2011 Nichols TW et al. Food Reactions and Their Implications in the Irritable Bowel Syndrome. IN: Integrative Gastroenterology. Mullin GE (ed) Oxford Press 2011 Mullin G et al. Testing for Food Reactions: The Good, the Bad, and the Ugly.NCP. 25:192, 2010 Heizer WD et al. The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review. J Am Diet Assoc. 109(7):1204-14, 2009 Questions? www.ecu.edu 6