1. Jolanda M. Denham, MD Pediatric Gastroenterology, Hepatology and Nutrition October 21, 2014 NON-CELIAC GLUTEN SENSITIVITY (when it’s not Celiac)

2. What we will discuss in the next hour (or so) Gluten Free is “In” What is the difference between Wheat Allergy, Celiac Disease and Non-Celiac Gluten Sensitivity (or Gluten Intolerance)? Why being gluten-free when not needed may not be a good idea

3. OBJECTIVES Discuss the differences between Wheat Allergy, Celiac Disease and Non-Celiac Gluten Sensitivity Explain the Pros and Cons following a Gluten- Free Diet for those without Celiac Disease

4. Gluten-Free is “IN” Gluten-free diet becoming an increasingly popular solution. The market grew at a compound annual growth rate of 28% from 2004 to 2008, to finish with almost $4.2 billion in retail sales in 2009. billion By 2017 the market is expected to reach about $6.4 billion in sales.

8. Gluten-Free is “in” “healthier” –#1 reason for consumers to buy gluten free foods is because a GFD is thought to be “healthier” –BUT….

9. There are questions…. Is it necessary? Is it harmful? Is it cost effective? Who will benefit? What does the science say?

11. Who benefits from a Gluten-Free Diet? Celiac Disease Wheat Allergy Non-Celiac Gluten Sensitivity

12. Celiac Disease  It is an autoimmune disease  It is triggered by the consumption of gluten  It affects the small intestine’s digestive process  Occurs in genetically susceptible individuals –Must have DQ2 and/or DQ8 positive HLA haplotype to have celiac disease, but –Just because one has DQ2 and/or DQ8 positive HLA haplotype does not mean they will get celiac disease –Very common in the US –Is necessary but not sufficient

13. Celiac Disease  Celiac disease is an autoimmune disease of the intestines caused by a permanent sensitivity to gluten in genetically susceptible individuals  OR in other words…. Ingestion of gluten results in the formation of antibodies against tissue transglutaminase (an enzyme found in the intestinal lining) – Can present with: Gastrointestinal symptoms Non-gastrointestinal symptoms Totally asymptomatic

14. Celiac Disease = Abnormal Lab Tests  Antiendomysial antibodies (EMA)  Anti tissue transglutaminase antibodies (TTG)  HLA typing  Deaminated Antigliadin antibodies (DGA)

15. Celiac Disease = Abnormal Endoscopy NodularityScallopingNormal Appearing Scalloping

16. Celiac Disease = Abnormal Biopsies

17. Wheat Allergy Immunoglobulin E (IgE) mediated immune reaction to wheat proteins Symptoms occur minutes to hours after gluten exposures Baker’s Asthma and Rhinitis – based on inhaling wheat flour Wheezing, cough, runny nose Food Allergy – based on eating wheat Hives, eczema Anaphylaxis (throat closing, inability to breathe) => DEATH

18. Wheat Allergy – IgE blood Tests  Component Reference Range Value  CORN, ALLERGEN <0.35 kU/L 8.44 (H)  EGG WHITE, ALLERGEN 100.00 (H)  MILK (COW), ALLERGEN 100.00 (H)  OAT, ALLERGEN <0.35 kU/L 57.20 (H)  PEANUT, ALLERGEN <0.35 kU/L 87.80 (H)  RICE, ALLERGEN <0.35 kU/L 4.74 (H)  SESAME, ALLERGEN 100.00 (H)  SOYBEAN, ALLERGEN <0.35 kU/L 56.00 (H)  WHEAT, ALLERGEN <0.35 kU/L 79.60 (H)

19. Wheat Allergy – Skin Prick Testing

20. Wheat Allergy – Treatment Avoid all wheat Avoid all wheat – your life may depend on it! Always carry the Epi Pen!

21.  But what if all my allergy and celiac testing are negative, I don’t wheeze or have hives when I eat wheat, but I feel awful when I eat gluten?  What about me?

22. Non-Celiac Gluten Sensitivity (say what?) Gluten reactions without identified allergic or autoimmune mechanisms Distress when eating gluten, improvement with GFD Occurs within few hours – few days to gluten exposure Normal labs Normal celiac titers (TTG, EMA) No IgA deficiency Normal IgE levels, skin prick testing to wheat Normal small intestinal biopsies

23. NCGS is not new…. Cooper, 1980 Small study of 8 women with abdominal pain, diarrhea and bloating 6 improved with GFD, but did not have celiac disease Karkinen, 2000 94 adults with abdominal pain after eating gluten 63% did not have celiac disease Within the past 5 years, 2 international consensus meetings (2011, 2012) on gluten-related disorders Better classifications, so can perform better studies Identify the questions to be answered

25. Non-Celiac Gluten Sensitivity Symptoms Abdominal pain Diarrhea Constipation Nausea/Vomiting GI Weight loss NEURO/PSYCH Headache Tingling/Numbness Brain Fog Fatigue Joint painDepression Bone, joint pain “Fibromylagia” Muscle cramps Leg numbness Leg tingling Anxiety Depression ADHD symptoms “Foggy mind” Headache Behavioral changes Fatigue Weight loss Mouth ulcers Rash Abdominal pain Flatulence Diarrhea Bloating Anemia

26. NCGS – Potential Causes Mice with NCGS have increased smooth muscle contractility in the small bowel wall, increased secretion of fluid into the small bowel Different composition of gut flora which triggers inflammatory response to gluten Certain non-gluten wheat proteins shown to increase immune reactions in the GI tract Sensitivity to food additives and preservatives Nitrates, glutamates, benzoates, sulfites, glutamates

27. FODMAPs Multiple food insensitivities (including wheat) may be due to intakes of high FODMAP foods Fermentable Oligo-, Di- and Mono-saccharides And Polyols Poorly absorbed short-chain carbohydrates Small size, rapid fermentation causes fluid and gas distention Causes abdominal pain, bloating, diarrhea Dairy Beans Certain Certain Grains, cereals – wheat, rye, barley Certain Certain Beans, fruits, vegetables and sweeteners

28. FODMAPs

29.  And So…..

30. Celiac Disease vs. Gluten Sensitivity vs. Wheat Allergy

32. Unnecessary GFD may not be benign…… Potential of nutritional deficiencies Low calcium, zinc, phosphorus, iron and B vitamins (folate, niacin, B12) Low in fiber – Fiber protective against heart disease and colon cancer Fiber protects against constipation Loss of prebiotic benefits Wheat provides 70-80% of Oligofructans, inulin Prevent against cancer, cardiovascular disease, inflammation Wheat may help lower triglyceride and lipid levels (small studies)

33. Unnecessary GFD may not be benign…… Inability to diagnosis Celiac Disease Health complications from not strictly adhering to GFD if you really do have celiac disease Self reported adherence to GFD in those even with celiac disease only 45-81%  Unnecessary hassle (wouldn’t you rather eat that cookie?) Unnecessary cost (wouldn’t you rather save for a trip?)