Biology and Genetics
Environment and Occupational Issues - Gluten and Allergen Health Risks
Background
Gluten is a wheat protein that can be found in numerous everyday food sources such as whole wheat bread, cakes, cereal, pasta, commercial dairy products and alcoholic beverages. Many people are aware of gluten and classify gluten free diets (GFD) as a fad. This is far from the truth as one of the most serious forms of gluten sensitivity, celiac disease, affects roughly 1% of the population most of who don’t know they have it. This is due to the wide individual variability of clinical signs and symptoms resulting from gluten exposure as well as the existence of latent, i.e. asymptomatic, forms of gluten sensitivity. This is of serious concern as long-term exposure to low levels of gluten in susceptible individuals may lead to chronic health problems, medical complications and increased mortality rates.
The adverse health effects associated with gluten exposure are specific to genetically predisposed individuals. Those who have variants of a specific gene, the human leukocyte antigen (HLA), are clearly associated with a predisposition to gluten sensitivity. Thus, the cascade of biological events that culminate in CD immune response involve a combination of genetic and environment factors. For instance, patterns of grain consumption have been compared to celiac disease prevalence around the world. It was noted that in the Far East and sub-Saharan Africa, low levels of gluten consumption parallel celiac prevalence. On the whole, the precise number of people suffering from gluten sensitivities is hard to estimate as many individuals do not suffer acute health effects or are misdiagnosed. This is depicted by the use of an ‘iceberg’ principle of CD prevalence as most cases go undetected.
Health Risk
Originally, gastrointestinal symptoms were thought to be the only health effects related to gluten exposure in sensitive individuals however current studies have revealed the possible role of gluten in triggering systematic immune reactions in the development of neurological dysfunctions. Another asymptomatic variant of celiac disease is dermatitis herpetiformis; characterized by the appearance of chronic soars and boils on the elbows, knees, lower back and, buttocks. Numerous other health effects have been associated with gluten sensitivities such as type 1 diabetes, autoimmune thyroiditis, autoimmune hepatitis, Sjogren’s syndrome, Addison’s disease, and rheumatoid arthritis; all of which are related to autoimmune dysfunction. Furthermore, exposure to gluten proteins in wheat based foods results in damaged intestinal lining and decreased absorption of nutrients such as calcium and iron increasing the risk of bone disease, anemia and malignancies. Namely, primary liver cancer as well as extra-intestinal and B-cell lymphomas have been observed in patients with celiac disease.
A report by the Food and Drug Administration compiled results from numerous food challenge studies and calculated a safe level of gluten below 1 mg which may be tolerated daily. This corresponds to less than 1ppm of gluten from daily food consumption that is deemed safe for even the most sensitive individual. That is, an average 30g slice of wheat bread contains roughly 4.8 grams (or 4800 mg) of gluten as the amount of gluten corresponds to 10% by weight. This illustrates the high risk of gluten exposure for sensitive individuals when comparing 0.4 mg << 4800mg. Gluten threshold study results are thus aligned with the 20ppm (corresponding to 0.6 mg) gluten content guideline for naturally gluten-free products by the Codex Alimentarius gluten-free standards.
Risk Management
The main way to manage risks associated with gluten exposure in sensitive individuals is to follow a strict gluten free diet (GFD). As a result prevention options include increased regulation of food labeling guidelines by government authorities, identification of susceptible individuals by means of population wide screening, educating the public on the importance of adhering to a GFD and the risks associated with noncompliance. Additionally, non-dietary therapies to reduce the adverse health risks of gluten exposure are currently entering clinical trial phases. Such therapies will alleviate certain inconveniences related to following a restricted diet by allowing occasional low does exposures if appropriate peptide inhibitors are taken simultaneously.
As risk management options targeting prevention of adverse health effects are preferred to the treatment of effects once they have occurred, focusing management efforts on improving diagnostic guidelines for gluten sensitivities should be addressed. What is more, celiac disease meets the World Health Organization (WHO) Criteria for general screening as it has a high prevalence, early diagnosis is difficult due to varying clinical symptoms between individuals, but once identified effective treatments are available.
There exist numerous diagnostic tests such as measuring serum anti-bodies specific to gluten subtype proteins, small bowel biopsy (SSB) and genetic screening for genes that predispose individuals to the risks associated with gluten exposure. SSB involves removal of tissue or cells from the small intestine to verify possible inflammation status or damages resulting in reduced intestinal digestion and absorption of nutrients. It is the gold standard for diagnosis, employed as verification of positive serology tests or primary means of diagnosis for acute cases of CD.
Due to limited cost analysis, screening guidelines have not been implemented. However, work by Shamir and others completed a cost-utility analysis and concluded that considerable costs will be saved in screening for gluten sensitivities and reducing the associated mortality rate. Once government authorities implement strict guidelines for select screening of gluten sensitivities in susceptible populations, early intervention with a gluten-free diet will reduce the magnitude of adverse clinical and morphological health effects. Finally, monitoring adherence to gluten free diets will provide a means of evaluating long-term screening benefits. Moreover, public awareness campaigns on the long list of diverse health effects related to gluten consumption, the importance of screening and ways in reducing exposure should be put in place to support screening efforts.
Useful Links
Celiac Disease and Gluten-free Diet Information Since 1995
http://www.celiac.com/
Canadian Celiac Association
http://www.celiac.ca/
U.S. Food and Drug Administration
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm265212.htm
Canadian Digestive Health Foundation
http://www.cdhf.ca/
Dr. Mark Hyman’s Article on Gluten
http://drhyman.com/gluten-what-you-dont-know-might-kill-you-11/
Further Reading
Administration, F. a. D. (2011). Health Hazard Assessment for Gluten Exposure in Individuals with Celiac Disease: Determination of Tolerable Daily Intake Levels and Levels of Concern for Gluten.
Agency, C. F. I. (2011). Project 1220 Enhanced Labelling for Food Allergen and Gluten Sources and Added Sulphites.
Anderson, R. P. (2008). Coeliac disease: current approach and future prospects. Internal Medicine Journal, 38, 790-799.
Paola Forabosco, S. L. N., Luigi Greco, Åsa Torinsson Naluai, Cisca Wijmenga, Päivi Saavalainen, Richard S. Houlston, Paul J. Ciclitira, Marie-Claude Babron, and Cathryn M. Lewisak. (2009). Meta-Analysis of Genome-Wide Linkage Studies in Celiac Disease. Hum Hered, 68(4), 223-230.
Raanan Shamir, O. H., Moshe Leshno. (2006). Cost-Effectiveness Analysis of Screening for Celiac Disease in the Adult Population. MEDICAL DECISION MAKING, 282-293.
Rewers, M. (2005). Epidemiology of Celiac Disease: What Are the Prevalence, Incidence, and Progression of Celiac Disease? Gastroenterology, 128, S42-S51.
Valerie Abadie, L. M. S., Luis B. Barreiro, and Bana Jabri. (2011). Integration of Genetic and Immunological Insights into a Model of Celiac Disease Pathogenesi. Annu. Rev. Immunol., 29(1), 493-525.
Contributors: Melissa Descoteaux
Last Reviewed: August 6, 2012
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