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Gluten Intolerance

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Gluten Intolerance 2/10/2016 Some Questions We Will Explore • What is with the gluten‐free fad? • Are people who complain of gluten intolerance or gluten sensitivity— Gluten Intolerance: without having celiac disease—hypochondriacs or attention‐seekers? • Do some people who do not have celiac disease react negatively to Madness, Myth, Medicine or Mystery? ingested gluten? • Is gluten‐free just another passing fad upon which the food industry is Lunch and Learn capitalizing? Em M. Pijl‐Zieber PhD, RN Faculty of Health Sciences University of Lethbridge When Did All This Craze Start? What Is Gluten? • Gluten is found in grains such as wheat, barley, rye, and a cross between wheat and rye called triticale • Gluten is a complex protein formed of two protein structures: gliadin and glutenin, connected by disulfide bridge • Gluten is the magical protein responsible for the capability for bread dough to rise and contain carbon dioxide What Is Gluten? What Is This Gluten‐Free “Fad”? • According to Agriculture and Agri‐Food Canada (2013): • "Gluten free" is the fastest growing food intolerance category • Celiac disease is recognized as one of the most common chronic diseases world‐wide (Health Canada 2008), affecting an estimated 1% (1/133) of Canadians, with less than 10% of people with celiac disease having been diagnosed. 1 2/10/2016 What Is This Gluten‐Free “Fad”? What Is This Gluten‐Free “Fad”? • According to Agriculture and Agri‐Food Canada (2013): • According to Agriculture and Agri‐Food Canada (2013): • Almost one third of Canadians (10 million) are looking for gluten‐free • Reasons for a gluten free diet: products (Canadian Celiac Association, 2013) (Hartman Group, 2013) What Clinicians Have Known What Clinicians Are Seeing • Narrow spectrum of gluten disorders: • A set of symptoms that in many ways looks like: • Celiac disease (1%) 98% of people are “normal” and • Irritable bowel syndrome • Wheat allergy (<1%) unaffected by gluten or wheat • Celiac disease • Wider range of intestinal diseases: • A set of symptoms that may also be: • Irritable bowel disease • Neurological – “brain fog”, fibromyalgia, ataxia Unrelated, but possibly influenced to • Colitis some degree, by diet (not gluten) • Not limited to the intestines – extraintestinal symptoms • Crohn’s disease …All in the absence of what we consider celiac disease, namely • Negative blood test, and/or • Negative histology (intestinal biopsy) (Volta, Caio et al., 2015) What Is Celiac Disease? What Is Celiac Disease? • Celiac disease is an immune reaction to eating gluten, a protein found in wheat, barley and rye. • Eating gluten triggers an immune response in the small intestine. This reaction produces inflammation that damages the small intestine's lining and prevents absorption of some nutrients (malabsorption). • The intestinal damage can cause weight loss, bloating and sometimes diarrhea. Eventually, the brain, nervous system, bones, liver and other organs can be deprived of vital nourishment. • A multi‐system autoimmune disorder, the manifestations (over 200 possible symptoms) of which respond to a strict gluten free diet 2 2/10/2016 What Is Celiac Disease? • Genetic, environmental, and immunologic components IMMUNOLOGICAL GENETIC ENVIRONMENTAL What Is Celiac Disease? • Testing for celiac disease: • Blood test (screening)—tTG (measure of serum IgA) • 90% accurate • Some people are IgA deficient, resulting in a false negative • Some physicians do not correctly use the test – should be a gateway to biopsy; fail to consider the patient’s presentation • Upper endoscopy and intestinal biopsy (diagnostic)—villous atrophy • Very accurate…if the affected part of the small intestine is biopsied – patchy versus “PVC pipe” • HLA DQ2 and HLA DQ8 – genetic test; 40% of North Americans will have the gene but only 0.5‐1.0% will develop celiac disease (Armstrong, Don‐Wauchope, & Verdu, 2011) What Is Celiac Disease? What Is Celiac Disease? • Based on this understanding of known wheat or gluten disorders, • Based on this understanding of known wheat or gluten disorders, patients are classified as: patients are classified as: Celiac Normal Celiac Normal 1% of population 98.7% of population 1% of population 98.7% of population (EVERYBODY ELSE) (EVERYBODY ELSE) Wheat Allergy Wheat Allergy .3% of population .3% of population 3 2/10/2016 What Is Celiac Disease? Does Non Celiac Gluten Sensitivity Exist? • Based on this understanding of known wheat or gluten disorders, • Scientific findings have had conflicting results patients are classified as: • Studies are compromised by: • No set definition of NCGS – wide range of symptoms, experiences • Patients self‐identify as NCGS and are thus enrolled in the study Celiac Normal • There are no biomarkers of NCGS – what are we measuring in these studies? 1% of population 99% of population More self‐report? (EVERYBODY ELSE) • What is the agent of harm: Gluten? Wheat? FODMAPs? • Pathological mechanism is not understood • Multiple food sensitivities are often reported (confounding) • Symptoms are similar, even identical, to celiac disease, and the severity of damage in the bowel (if any) does not correlate well to severity of symptoms Di Sabatino and Corazza, 2012; Lebwohl and Leffler 2015 Does Non Celiac Gluten Sensitivity Exist? Molina‐Infante, Santolaria et al., 2015 Biesiekierski, Newnham et al., 2011 Biesiekierski, Peters et al., 2013 Di Sabatino, Volta et al., 2015 Peters, Biesiekierski et al., 2014 Shahbazkhani, Sadeghi et al., 2015 Aziz et al, 2015 Kabbani et al, 2014 Bonciolini et al, 2015 Marietta & Murray, 2012 ? Brottveit et al, 2012 Sbarbati et al, 2003 Hadjivassiliou et al, 2010 Sapone et al, 2010; 2011 ? Hollon et al, 2015 Vazquez‐Roque et al., 2013 Ihara et al, 2006 Biesiekierski & Iven, 2015 Elli et al, 2015 Fasano, 2014 Hadjivassiliou et al, 2006 Isasi et al, 2014 Kheder et al, 2012 Khwaja et al, 2015 Lionetti, Leonardi et al., 2015 Tonutti & Bizzaro, 2014 Anecdotes Vandenplas, Benninga et al., 2015 Volta et al, 2013 Gaesser and Angadi, 2015; Sapone, Bai, et al., 2012 Does Non Celiac Gluten Sensitivity Exist? Does Non Celiac Gluten Sensitivity Exist? Yikes. Am I a Thank goodness hypochondriac? she believes me. Your tTG test is Am I imagining I thought I was Your tTG test is negative. negative, but I am my symptoms? going nuts. Go home and have a intrigued by your doughnut! experience and symptoms. I’m going to look into this for you. 4 2/10/2016 Does Non Celiac Gluten Sensitivity Exist? Does Non Celiac Gluten Sensitivity Exist? • One theory: Gluten cannot be processed by humans • Another theory: Wheat itself has changed, or how it’s used • “Wheat Belly” vilifies wheat as unfit for human consumption • Novel variants of wheat that are known to contain high amount of toxic • Gluten is vilified around every corner these days and blamed for many gluten peptides potentially harmful to the integrity of the enteric mucosa? disorders • Celiac‐triggering gluten proteins are expressed to higher levels in modern cereals while • Most people can tolerate gluten and wheat well, as we have evolved eating non‐triggering proteins are expressed less. • Sophisticated hybridization techniques have been used to produce new strains of gluten‐containing grains modern wheat, the most high‐yielding of which have since made their way into human foods in the absence of animal or human safety testing. • Mechanization of farming and the growing industrial use of pesticides? • Overall reduced time of dough fermentation resulting in a higher content of toxic gluten fractions in bakery products? The Paleo Babe (de Lorgeril & Salen, 2014; Fardet, 2015; Volta, Caio et al., 2015) Does Non Celiac Gluten Sensitivity Exist? Does Non Celiac Gluten Sensitivity Exist? • Theory: Media has fanned the flames of gluten sensitivity • A theory with promise: Based on the fact that the degree of intestinal • Increasing awareness among non‐medical people damage and the severity of a person’s symptoms are poorly • Increasing awareness among clinicians correlated, Dr. Fasano proposes this view: • Increased market for gluten free products (although often with high rates of GLUTEN SENSITIVITY + AUTOIMMUNE = CELIAC DISEASE cross contamination that make many food items unsafe for people with celiac disease) GLUTEN FREE AUTOIMMUNE “(no hidden ingredients)” GLUTEN But…… AUTOIMMUNE SENSITIVITYGLUTEN + = SENSITIVITY GLUTEN SENSITIVITY (Volta, Caio, Stanghellini, & De Giorgio, 2014) Does Non Celiac Gluten Sensitivity Exist? Does Non Celiac Gluten Sensitivity Exist? • An emerging theory: “Leaky gut” (don’t laugh) • Theory: A mixed bag of potential mechanisms • Damaged to small intestine, in this case by the presence of gluten • Overlapping condition with functional bowel disorders (IBS) • Changes of the gut microbiota might favor the inflammatory response to • Overlapping condition with other food hypersensitivities gluten • Other wheat components • Zonulin has an increased expression in patients with celiac disease; might this • FODMAPS also be a factor in NCGS? • Unique immunology, different from celiac disease • Gliadin has been shown to activate zonulin signaling (to open gap junctions) • Similarities: Gluten causes inflammation, altered gut microbiome, T cells (in animal irrespective of the genetic expression of autoimmunity, leading to increased models) intestinal permeability to macromolecules • Data is conflicting regarding small intestine permeability, however. (Drago, El Asmar, et al, 2006; Fasano, Not, et al., 2000; Lammers, Lu, et al, 2008; Volta, Caio et al. 2015) (Ejsing‐Duun et al., 2008; Hansen
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