Gut Grief: A Critical Look at Non-celiac Gluten Sensitivity (NCGS) & MORE Christine Kessler ANP-BC, CNS, BC-ADM, CDTC, FAANP Metabolic Medicine Associates King George, Virginia My Industry Associations Novo Nordisk advisor and speaker (obesity only) Astra Zeneca T2DM advisor Medtronic Insulin pumps and continuous glucose monitoring (outpatient and inpatient) 3 Objectives Review the prevalence and epidemiology of NCGS Compare the pathogenesis and presentation of NCGS, celiac disease and wheat allergies Discuss diagnosis, assessment and treatment of NCGS Discuss the effects of gluten on the intestinal mucosa 1
Is Gluten-Free Just A Food Fad Are We A Nation of Gluten Intolerants? So What Is Gluten-gut-immune Connection Gliadin protein portion of gluten-has molecular similarity to thyroid tissue! It crosses the intestinal barrier--zonulin antibody reaction ensues (reaction can last days to 6 months per exposure) Promotes autoimmune thyroid dz (mostly Hashimoto s) The celiac lab tests may or may not be positive FYI those with Hashimotos have multiple sensitivities to food cow milk, soy, corn, wheat. What is Gluten? 200 proteins comprise the gluten family. Gluten is a matrix formed by the proteins gliadin and glutenin 2
Gluten in the Food Supply Wheat is the primary source of gluten in the US food supply Breads, pasta, tortillas, crackers, cookies, cakes, etc. Provides elasticity to dough---now with added vital gluten Other foods containing gluten include: Couscous, bulgur, farina Beer, ale, lager Malt or malted foods: malt extract, malt vinegar (used in some pickles), malted milk, etc. Coating on French fries Other sources: seasonings, broths, soy sauce, sausage, hot dogs, deli meats, candies, medications, lip stick, play dough Wheat Is The Latest Dietary Villain Close to 30% of US adults* are interested in cutting down or avoiding gluten in their diets. Most are not doing so out of medical necessity. 15 billion dollar business (50% up since 2103) Americans consume 134.4 lbs wheat annually No change in 50 years But...is gluten or wheat really the cause of all the obesity and the rise in autoimmune disease? *NPD Group/Dieting Monitor, 52 week data year ending January 30, 2013 Gluten Is The Latest Dietary Villain Close to 30% of US adults* are interested in cutting down or avoiding gluten in their diets. Most are not doing so out of medical necessity. 15 billion dollar business (50% up since 2103) Americans consume 134.4 lbs wheat annually No change in 50 years But...is gluten or wheat really the cause of all the obesity and the rise in autoimmune disease? *NPD Group/Dieting Monitor, 52 week data year ending January 30, 2013 3
10 Gluten Facts > 95% can consume and tolerate gluten Can lead to intestinal inflammation & changes in microbiota Those over 65 more intolerant? Gluten intolerants fall onto 3 categories: Celiac Disease (an autoimmune disease) Wheat & grain allergies Non-celiac Gluten Intolerance (yeah, it s real) True percentage not really know: 1 to 9% Many may have a problem with the CARB in wheat FODMAPS (Fermentable oligo-dimonosaccharides & Polyols) Fructans Wheat, garlic & artichokes Fructose fruit Lactose Some dairy products Galactans Some legumes 12 Let s Quickly Look At The King Of Gluten Sensitives CELIAC DISEASE 4
What Is Celiac Disease (CD) Chronic autoimmune disease of the small intestine triggered by the ingestion of gluten Causes intestinal inflammation Impairs absorption of nutrients Contributes to systemic complications Celiac Disease Fast Facts CD is a genetic autoimmune disease that damages the villi of small intestines and interferes with absorption of nutrients 1:133 Americans have it (1% of population) 83% go undiagnosed. Affects all genders, ages, race The United Kingdom, Sweden and Germany with higher prevalence (1.5%) 30-40% of all people in the U.S. carry the gene for celiac disease. Only 1-2% of those people have the gene activated. Celiac Disease Fast Facts CD is a genetic autoimmune disease that damages the villi of small intestines and interferes with absorption of nutrients 1:133 Americans have it (1% of population) 83% go undiagnosed. Affects all genders, ages, race The United Kingdom, Sweden and Germany with higher prevalence (1.5%) 30-40% of all people in the U.S. carry the gene for celiac disease. Only 1-2% of those people have the gene activated. 5
More CD Facts Gluten is the single major environmental factor that triggers CD The enzyme tissue transglutaminase (ttg) is the autoantigen Or transglutaminase2 autoantibodies Has specific association with class II haplotypes of HLA DQ2 (haplotypes DR-17 or DR5/7) and, to a lesser extent, DQ8 (haplotype DR-4). 3-17% 1 st degree relatives are celiacs 10-25% have other autoimmune dz; risk of lymphoma If villi are damaged, vitamins, minerals, calcium, carbohydrates, protein, and fats are not absorbed well 6
HISTOLOGY ENDOSCOP Y CELIAC DISEASE Normal Scalloped Gluten-free diet Increased IEL Villous atrophy Recovering Clinical Manifestations (not consistent) Gastrointestinal ( classical ) Non-gastrointestinal (atypical ) Asymptomatic 21 7
The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion Silent Celiac Disease Latent Celiac Disease Normal Mucosa Genetic susceptibility: - DQ2 (1 and 3), DQ8 Frank A. Hamilton, M.D., MPH Positive serology National Institutes of Health National Institute of Diabetes, Digestive and Kidney Diseases Signs and Symptoms Common (child?) Diarrhea Fatigue Borborygmus Abdominal pain Weight loss Abdominal distention Flatulence Uncommon (adult?) Osteopenia/ osteoporosis* Abnormal liver function Vomiting Iron-deficiency anemia Neurologic/psych problems Constipation Nausea 38 % or more may be asymptomatic Celiac Disease in Children 8
Major Complications of Celiac Disease Short stature Dermatitis herpetiformis Dental enamel hypoplasia Recurrent stomatitis Fertility problems Cancer...not breast? Osteoporosis Gluten ataxia and other neurological disturbances anemia Refractory celiac disease and related disorders Intestinal lymphoma Dermatitis herpetiformis National Digestive Diseases Information Clearinghouse (NDDIC) 27 9
Is NCGS Real? What about Ncgs? 30 NCGS Symptoms Presents with IBS-like and neuropsychiatric symptoms. Those with IBS (15-20% of population) have greater reports of gluten sensitivity Presents within hours to days Bloating and abdominal pain (72-77%), diarrhea, constipation (40%) Headache, foggy mind, fatigue (34%) Depression/anxiety (22%) Anemia (20%) Numbness in legs, arms & fingers (20%) J oint/muscle pain (11-28%) 10
Wheat Allergies Presents within minutes to 2 hours Pruritic rash, hives, swelling of tongue, rhinitis, abdominal cramps, vomiting, diarrhea, constipation anayphylaxis A few points other food allergies/ alolergies Food allergies/intolerances You will be surprised! What you eat Most common food culprits Additives Food growing practices What is added to your food (gluten, numerous enhancers ) What your meat eats (what we eat, growth hormones, antibiotics) & stress 11
Serologic Performance Characteristics Clinical Suspicion Duodenal Biopsy American Gastroenterology Association- -The AGA Institute Diagnosis 1 st : Physical exam and blood testing Anti tissue transglutaminase antibodies (TTG/A) 93 sensitivey/98% specificity) Antiendomysial antibodies (EMA) lacks specificity Antigliadin antibodies (AGA) other uses 2 nd : Duodenal biopsy (then genetic eval?) 3 rd : Implement gluten-free diet**** Gluten sensitivity stool panel (immune responses and $$$) http://www.csaceliacs.org/celiac_diagnosis.php Tips to testing Pt should consume gluten for 2-4 weeks prior If not: eat 3 g gluten (2 pieces bread) for 2 weeks then repeat labs 12
Testing for NCGS & WA NCGS suggest IgG antigliadin antibodies (AGA) Dx by exclusion negative CD serology No histologic evidence of villous atrophy! Variable HLA status Variable presence of first generation anti-gliadin antibodies Go gluten free for 6 weeks & check symptoms WA: skin prick tests and allergen-specific IgE along with hx, sx/sy, food challenges Catassi C, Bai J, Bonaz B, et al. Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders. Nutrients. 2013;5(10):3839-3853 Treatment for CD Lifelong avoidance of gluten--strict Oats are tolerated by most controversy (d/t growth/processing) Daily multiple vitamin and calcium Folic Acid for women of child-bearing age No initial role for bisphosphonates Dexa? Treatment of NCGS Avoidance of gluten may not be as strict as CD (no need to fear occult sources) Food-symptom diary check reaction to other foods FODMAPS: milk, veggies, besides wheat honey, legumes, glutamates, sulfites and nitrates May try reintroduction of gluten in 1 year 13
Dose-dependent Effect of Gliadin on Small Bowel Dose of Gliadin Symptoms Permeability Intestinal Biopsy 10 mg No -- Normal 50 mg* 100 mg Yes No -- Normal 500 mg Yes Increased *capsule of gluten Minimal changes Minimal changes More pronounced changes Catassi et al. GUT 1993; 34: 1515 Ciclitira et al. Clin Sci 1984; 66: 357 Catassi et al. Gastroenterol 2005;128:A253 OVERLOOKED GLUTEN SOURCES Ales Beer and Lagers Bouillon Cubes Breading Brown Rice Syrup Coating Mix Communion Wafers Croutons Candy Some Chips/Potato chips Luncheon Meats, hot dogs, salami, sausage French Fries Gravy Pasta Rice Mixes Seasoned Tortilla Chips Soup Base Stuffing Self-basting Poultry Imitation Bacon/Seafood Soy Sauce Marinades Thickeners Herbal Supplements, Prescription Meds Over the Counter Meds Vitamin and Mineral Supplements Lipstick Lip Gloss and Balms Play Dough* (hands must be properly washed after playing with) Capsule coatings Meds, Gluten, Gut OH MY! Many medications have gluten sources/ contamination in their coating (like maldextrin) Consider the fillers! Corn starch, lactose and modified food starch A real problem with thyroid hormone replacement: Tirosint, Lannet and Mova levothyroxine brands, and Nature thyroid have fewest additives Synthroid has cross-contamination risk 14
43 Watch out for crosscontamination 44 Working Up Gluten Sensitivity Diagnosis based on exclusion criteria while on gluten containing diet Symptoms on and off gluten Negative celiac specific serology No histologic evidence of villous atrophy! Variable HLA status Variable presence of first generation anti-gliadin antibodies Wheat allergy excluded Catassi C, Bai J, Bonaz B, et al. Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders. Nutrients. 2013;5(10):3839-3853 45 Gluten Sensitivity Workup 1st: Physical exam and blood testing CD: Antiendomysial antibodies (EMA) (under 5yrs) Immunoglobulin A (IgA) anti-tissue transglutaminase (ttg) used to monitor compliance with a gluten-free diet. Antibody levels return to normal within three to 12 months of starting a gluten-free diet Wheat allergies: Allergy skin testing, IgE NCGS (above negative) Antigliadin antibodies (AGA) is this accurate? Kelly, CP. Diagnosis of celiac disease. In: UpToDate, Lamont, JT (Ed), UpToDate, Waltham, MA. Accessed on April 15, 2015). 15
46 Treatment Challenges Gluten-free foods are limited, and frequently unavailable. Gluten-free foods cost 2-3X that of normal foods. Unfortunately, purchase of gluten-free products is rarely covered by health insurance. Strict adherence to a gluten-free diet essential in can have an extraordinary outcome in CD Treatment Challenges Gluten-free foods are limited, and frequently unavailable. Gluten-free foods cost 2-3X that of normal foods. Unfortunately, purchase of gluten-free products is rarely covered by health insurance. The good news is that strict adherence to a glutenfree diet can have an extraordinary outcome Source:www.glutin.net FDA Gluten Free Labeling FDA has no current definition for gluten-free Proposed definition of gluten: proteins that naturally occur in wheat, rye or barley or a hybrids of these. Voluntary labeling Read label ingredients! 16
GLUTEN CONTAINING GRAINS TO AVOID Barley Barley malt/extract Bran Bulgur Couscous Bromated or Durum Flour Einkorn Emmer Enriched or Self Rising Flour Farina Faro Graham Flour Kamut Matzo Flour/meal Orzo Panko Phosphated Flour Rye Seltan Semolina Spelt Triticale (cross between wheat/rye) Udon Wheat Wheat Bran Wheat germ Wheat starch GLUTEN FREE GRAINS AND STARCHES Amaranth Arrowroot Buckwheat Corn Flax Flours made from nuts, beans and seeds Millet Montina Potato Starch Potato Flour Quinoa Rice Rice Bran Sago Sorghum Soy (soya) Tapioca Teff Dr. Becky Domokos-Bays, RD SNS, Director, Food and Nutrition Services, Alexandria City Public Schools 51 Summary NCGS is real (uncertain prevalence) Gluten is not the only culprit remember often multiple food intolerances Differentiate between CD, allergies and NCGSdon t assume Diet modification is the primary treatment Gluten free diets have not been proven to reduce the incidence of autoimmune disease and weight loss 17
52 http://gastro.ucla.edu/site.cfm?id=281 REFERENCES www.celiachealth.org www.celiac.org www.glutenfree.com Camtasia c et al. Non-Celiac Sensitivity: The New Frontier of Gluten Related Disorders. Nutrient. 2013 Oc; 5(10): 38839-3853 Castassi C et al. Diagnosis of non-celiac gluten sensitivity (NCGS): The Salerno Experts Criteria. Nutrients. 20156. 7(6): 4966-4977 References Fasano a et al. Non-celiac Gluten Sensitivity. Gastroenterology 2015, 148:1195-1204 Guandalini S. differentiating foods allergies from food intolerances. Curr Gastroenterol Rep, 2102; 13(50: 426-434 Kessler C. Gut Grief: The truth about gluten sensitivity. Clin Reviiews 2016 Mayo Clinic Staff. "Celiac Disease." Mayo Clinic. Mayo Foundation for Medical Education and Research, 2012. Web. 14 Mar. 2012. <http://www.mayoclinic.com/health/celiac-disease/ DS00319. <http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/>. Rubio-Tapia A et al. ACG clinical guidelines: diagnosis and management of celiac disease.j Gastroenterol 2013:108-656-76, Scanlon SA, Murray JA Update on celiac disease etiology, diffe3re3ntial diagnosis, drug taerets, diet. J Am Coll Nutr. 2014; 33(1):93-54 Sanders D, Aziz i. Non celiac wheat sensitivity: Separating the wheat from the chaff. Am J Gastroenterol. 2012; 107:1908-1912. Volta u. et al. Non-celieac gluten sensitivity: questions still to be answered despite increasing awareness. Cell & Mol Immun. 2013. 10:383-392. 18
So are you ready to end this? OK ckessler@maranatha.net 19