An Integrative Approach to Celiac Disease and Gluten Sensitivity. Stephen Donnelly, DO, FAAP. May 24, 2012

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1 An Integrative Approach to Celiac Disease and Gluten Sensitivity Stephen Donnelly, DO, FAAP May 24, 2012

2 Objectives Understand the difference and relationship between Celiac disease and Gluten sensitivity Understand who is at risk for these conditions Review the complex symptoms Testing Management (traditional and integrative) Explore a gluten-free menu

3 What is Celiac Disease? Autoimmune disorder triggered by the ingestion of gluten Immune system attacks the intestinal lining resulting in inflammation and reduced nutrient absorption (Endoscopy shows abnormalities). Classic symptoms: Diarrhea, weight loss, and malnutrition BUT there is a whole spectrum of syndromes

4 What is Celiac Disease? Autoimmune disorder triggered by the ingestion of gluten Upon exposure to gliadin, a component of gluten, the enzyme tissue transglutaminase modifies the protein, and the immune system cross-reacts with the small-bowel tissue, causing an inflammatory reaction. Immune system attacks the intestinal lining resulting in inflammation and reduced nutrient absorption (Endoscopy shows abnormalities). Classic symptoms: Diarrhea, weight loss, and malnutrition BUT there is a whole spectrum of syndromes

5 What is Gluten Sensitivity? A state of heightened immunologic responsiveness triggered by ingestion of gluten in genetically susceptible people, BUT it does not present as an autoimmune gut lining problem. (Endoscopy usually normal) Can have similar symptoms as CD, both gastrointestinal and beyond Usually less severe

6 Celiac Disease Celiac Disease An autoimmune disease triggered in genetically- susceptible individuals by the ingestion of the gluten proteins in wheat, barley, and rye Diagnosis historically based on pathologic changes in small intestine Gluten Sensitivity Probably part of CD spectrum Diagnostic criteria controversial, but literature supports elevated serum antibodies without clear GI pathology *Dickey, Proceedings of the Nutrition Society, 2009

7 Innate versus Adaptive Immunity Human Physiology Tenth Edition Stuart Ira Fox

8 Prevalence Previously thought to be a rare, inherited syndrome of childhood Used to be 1 case in 10,000 people Now 1 in 100 Americans 4 fold increase in past 50 years Estimated 2.18 million Americans affected 0.5 1% of U.S. Population 10x higher than previous estimates Arch Int Med 2003; 163(3): Lancet. 1994; 343:200-3

9 Why the increase? Gluten content of wheat 50x greater than 50 years ago. A society built on weak digestion Overabundance of convenient and processed foods

10 An evolving gut environment.. Eat on the run New proteins (Wheat, Dairy, pasteurization) Sugar, Nutrient dense foods Different bacteria Less fiber More Rx (Antibiotics, Acid blockers, Steroids) Cordain L. Origens & Evolution of the Western Diet: Health Implications for the 21st Century. Am J of Clinic Nutr. 2005

11 Prevalence Higher than 1% in certain groups: Type 1 Diabetes Down's Syndrome Autoimmune Thyroid Disorders Unexplained Infertility Neurological Disorders (Migraine, Epilepsy, Autism,...) Iron Deficiency Anemia Osteoporosis Psoriasis

12 Iceberg model

13 What is Gluten anyway? Gluten is a gummy substance produced during the processing of gluten containing grains: Wheat, barley, rye, and spelt

14 What is Gluten Anyway? Gluten is derived from the Latin word glue. It is the protein that makes dough stretchy. It is a type of protein, not a specific protein. Wheat ---> Gliadin Rye ---> Secalin Barley ---> Hordein Oat --->Avenin* Rarely bothers people with CD or GS* *Unless contaminated

15 Symptoms (Celiac Ds) Classic: Diarrhea Weight loss Malnutrition Latent Isolated nutrient deficiencies without gastrointestinal symptoms Mild weakness Bone pain Canker sores

16 Symptoms (Celiac Ds) Chronic diarrhea Abdominal distension (bloating/pain) Weakness Malabsorption Skin lesions/rash Anemia Osteoporosis Short stature Infertility Neurological complaints

17 Symptoms (Gluten Sensitivity) Bloating/stomach cramps Diarrhea/constipation Joint pain Itchy skin lesions Chronic Fatigue Migraine/ headaches Peripheral Neuropathy Often diagnosed with: Irritable Bowel Syndrome Chronic Fatigue Syndrome Fibromyalgia Eczema Depression/ anxiety

18 Symptoms CD/GS 38% of patients are asymptomatic Non-specific for the first few decades Fatigue, mood issues, insomnia, mild GI symptoms Then.....a trigger!

19 Trigger An insult such as... Intestinal infection Surgery Any trauma/ stress Leads to... Compromised intestinal lining/barrier function Intestinal inflammation Gluten peptides cross intestinal lining Initiate a cascade of inflammatory responses AGA Institute, Gastroenterology 2006

20 Then...

21 Malabsorption Syndromes Minerals Iron Resulting in/ Affecting: Anemia, fatigue Calcium Osteopenia, osteoporosis Zinc Immune deficiency, hair loss, skin lesions, infertility

22 Malabsorption Syndromes Vitamin Deficiencies B-12 Resulting in/ Affecting: Anemia, fatigue, neuropathy, mood disorders Fat soluble vitamins A D E K Anemia, reproductive, immune, visual disorders Bone metabolism, growth, and Immune disorders Inflammation, neuropathies Bleeding disorders, easy bruising

23 Osteopenia/ Osteoporosis Calcium and vitamin D malabsorption 40 70% adults with CD have low bone mineral density Skeleton will remineralize if strict gluten-free diet adhered to along with appropriate supplementation Gut 1996; 38:322-7 Aliment Pharmacol Ther 2000; 14:35-43

24 Gastrointestinal Conditions Symptoms: Reflux, bloating, abdominal pain, gas, Irritable Bowel Syndrome Chronic GI inflammation leads to: Diarrhea Bacterial overgrowth Secondary lactose intolerance

25 Skin Manifestations Dermatitis Herpetiformis Psoriasis Hair loss Intensely itchy rash

26 Neuropsychiatric Manifestations Peripheral neuropathy Multiple Sclerosis (inconclusive, but shared antibodies) Ataxia Migraine/ headache Epilepsy Depression Anxiety

27 Endocrine Manifestations Diabetes 2 10% of patients with type 1 diabetes have Celiac DsRate 10 33x the general population Thyroid disorders Both hyper- and hypo-thyroidism 10 15% of all CD have subclinical hypothyroidism Systemic lupus erythematosis (SLE) Endocr Rev Aug; 23(4):

28 Infertility Female Male Both Celiac disease found in 4 8% of unexplained infertility Zinc deficiency abnormal ovarian development, miscarriage, IUGR, Selenium deficiency subfertility Zinc deficiency abnormal sperm function Hyperprolactinemia impotence and loss of libido

29 Dental & Oral Manifestations Dental enamel defects brownish yellow discoloration on central incisors Aphthous oral ulcers (canker sores) 5% found to have undiagnosed celiac disease

30 Cancer Dramatically increased GI cancer rates 33x greater for small intestinal carcinoma 11.6x greater for esophageal cancer 9x greater for non-hodgkin's lymphoma Up to 15% of those with untreated or refractory Celiac disease will develop GI carcinoma or lymphoma N Engl J Med. 1996; 334(18): Am J Med 2003; 115(3): 191-5

31 Diagnosing Celiac Ds. Four primary blood tests: IgA anti-endomysial antibody (EMA) Highly specific IgA tissue transglutaminase (ttg) Specific marker for Celiac Disease Total IgA antibodies To determine if IgA deficiency is present IgG tissue transglutaminase If IgA deficiency is present

32 Diagnosing Celiac Disease *** The Gold Standard is still intestinal biopsy*** But many may have latent presentation Biopsy only positive when villi are gone Anti-gliadin antibodies (AGA) are still useful in diagnosing gluten sensitive neurologic damage Deamidated Gliadin Peptide (DGP) Antibodies, IgA: Anti-DGP test is a relatively new test that may be positive in some people with celiac disease who are anti-ttg negative, including children less than 3 years old.

33 Genetic Markers 40% of population has HLA-DQ2 or HLA-DQ8 >99% of pts w/ CD have HLA-DQ2 or HLA-DQ8 If these genetic markers are absent, celiac disease is unlikely Negative predictive value near 100% AGA Position Statement. Gastroenterology, 2006

34 Genetics HLA DQ2 homozygosity associated w/ more severe complications of CD More severe clinical presentation/younger age/intestinal damage Refractory CD EATL (enteropathy associated T-cell lymphoma) Identification of DQ2 homozygosity may help identify pts at risk for more severe complications

35 Treatment Strict avoidance of Gluten Only 100 mg of gluten per day is enough to cause mucosal damage to the intestine. This is 1/10 th of a gram 1 piece of pizza is ~ 2,000 mg of gluten

36 Treatment Rx: 100% Gluten-free diet for life Long recovery period often takes up to 2 4 years to intestinal lining to improve Incomplete dietary avoidance -EVEN WITH IMPROVED SYMPTOMS leads to heightened immune responses

37 Elimination Diet Full elimination diet: Take out several suspected foods at the same time for 4 6 weeks. Add back in one-by-one to test. Targeted elimination diet: Take out single food x 4 6 weeks and look for improvements

38 What to avoid in Gluten elimination diet... Wheat in all forms Rye Bread, pasta, cookies, crackers, cereals, flour tortillas, etc. Barley -including malt oatmeal

39 Wheat...aka Wheat -red winter, all purpose, durum, semolina, Kamut -a relative of durum wheat. Triticale -hybrid of wheat (Triticum) and rye (Secale) Spelt -an ancient wheat hybrid

40 But guess where else... Soy sauce Beer Ketchup, mustard Deli meats Protein powder Imitation seafood Seitan Thickeners Carmel coloring modified food starch Soup bases Stamps and glue

41 The Oatmeal Controversy... Oat is a different species and family...but Cross contamination... Most oatmeal produced in North America is produced in facilities that produce wheat products OR have fields where crops are rotated with wheat Mixed research data exists on oatmeal tolerance for Celiac patients Guidelines still recommend avoidance of oatmeal

42 So what to eat... Safe grains: Rice, amaranth, buckwheat, corn, millet, quinoa, sorghum, teff, oats*

43 So what to eat... Gluten-free starches for flour alternatives: Cereal grains: amaranth, buckwheat, corn (polenta), millet, quinoa, sorghum, teff, rice (white, brown, wild, basmati, jasmine), montina (Indian rice grass) Tubers: Arrowroot, jicama, taro, potato, tapioca (cassava, manioc, yucca) Legumes: Chickpeas, lentils, kidney beans, navy beans, pea beans, peanuts, soy beans Nuts: Almonds, walnuts, chestnuts, hazelnuts, cashews Seeds: Sunflower, flax, pumpkin

44 Treatment Healing: (body, mind, spirit) Nutrition Gluten-free diet Modified Mediterranean or Anti-inflammatory Diet Test for deficiencies Iron, folate, B-vitamins, homocysteine,vitamin D, Calcium Thyroid, glucose, lipids Dexa-scan -(bone mineral density) Exercise -Yoga, Tai Chi,

45 Healing the gut Supplements to consider... Probiotics Vitamin D3 Vitamins/minerals (iron, folate, B-vitamins zinc, magnesium, calcium..) L-Glutamine Omega-3's (DHA, EPA, ALA) -anti-inflammatory DGL (deglycyrrhizinated licorice) Digestive enzymes Aloe vera juice

46 Intestinal Dysbiosis in Celiac Ds. - Increased Levels - Bacteroides Clostridium leptum E. Coli Staphylococcus - Decreased Levels - Bifidobacterium Lactobacillus PROBIOTIC: Lactobacillus acidophillus and Bifidobacterium billion CFUs /day GF/dairy free

47 Vitamin D BMD in up to 70% of celiac pts Malabsorption Ca, Vit D, Mg Vit D absorbed in duodenum Bone health, immune modulation, diseases Goal serum levels ng/ml

48 Stomach Acidity 30-40% of CD pts suffer from dyspepsia* Reflux is common in CD PPI's (Prevacid, Prilosec, Nexium, Aciphex, Protonix,) may be commonly prescribed... RECONSIDER!

49 Stomach Acidity Acidic ph necessary for: Nutrient digestion and absorption Limiting entry of pathogens Activating digestive enzymes PPI s have been shown to: Increase risk of fractures Increase C-diff associated diarrhea Increase risk of hospital-acquired pneumonia Consider alternative: DGL

50 Zinc HCL Acid depends on Zinc for its secretion Needed for IgA and immune function Beneficial for shortening infectious diarrhea and pneumonia in kids.

51 Percentage of all Individuals >2 yo NOT meeting 100% US Recommended Dietary Allowances Zinc 73.3% Calcium 65.1% Magnesium 61.6% Vitamin A 56.2% Vitamin B6 53.6% Iron 39.1% Vitamin C 37.5% Folate 33.2% Thiamine 30.2% Riboflavin 30.0% Cordain L. Origens & Evolution of the Western Diet: Health Implications for the 21st Century. Am J of Clinic Nutr. 2005

52 Gluten-Free Foods Often not fortified with vitamins and minerals So even when gut is healed there is a risk for nutrient deficiencies Recommend daily multivitamin with minerals

53 Quiz Once free of symptoms, patients may re-introduce 1 or 2 gluten-containing foods every week without villi damage. False. Even when celiac patients aren't experiencing any symptoms, the ingestion of gluten will continue to damage the intestine. True or False?

54 Quiz Most gluten free products are enriched with vitamins and minerals especially needed by Celiac patients. True or False? False -Most are not fortified and patients with celiac disease need some sort of supplementation or increased food sources of B- vitamins, Vitamin D and possibly iron.

55 Quiz If a product is labeled "wheat free" this does not mean that it is "gluten free." True or False? True. There are other food components like rye, malt or barley or commonly used food additives that are not wheat products, but do contain gluten and must be avoided by Celiac patients. It is important to learn how to interpret ingredient lists on labels.

56 Quiz A patient with celiac disease can consume as many "gluten free" labeled products as they like. True or False? False. "Gluten free" means that there is no more than 20ppm of gluten per serving, so if a patient were to eat multiple servings or multiple "gluten free" products, there is a chance that this would add up to more than a tolerable level of gluten.

57 Celiac Disease vs. Gluten Sensitivity Two paths to the same result

58 Summary CD and GS are common CD may present in an atypical fashion and GS is part of a spectrum The long term sequelae of CD/GS are severe Malignancy, CVD, autoimmune disease, nutrient deficiencies, neurologic disorders, infertility etc. Simple lab tests are available to support the diagnosis, but the clinical picture is important Strict life-long avoidance of gluten along with healthy nutrition and supplements can help to heal the gut and improve quality of life for patients with CD/GS

59 Resources Celiac.com ( Living Without magazine ( Celiac Disease Foundation ( Gluten Free Living magazine ( University of Maryland Center for Celiac Research ( Children's Digestive Health and Nutrition Foundation ( What? No Wheat? Enterprises (

60 Resources Recommended Book: Real Life With Celiac Disease Melinda Dennis, MS, RD, LDN, and Daniel A. Leffler, MD.

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