Alan da Rocha Brum, BSC (PSYCH), M. Ed.
Naturopathic medical student at the Boucher Institute of Naturopathic Medicine, with special interest in the digestive system.
Nowadays, gluten free diets have become popular, but there is a lack of education and a lot of confusion about Celiac Disease. What are the key points when gluten needs to be eliminated?
Have you ever left the doctor’s office with a plan for food restriction? If you have heard “we will need to change your diet” or “you are allergic to a specific allergen and you need to avoid it”, you know how those words can be overwhelming.
Food restrictions can be a challenging adjustment process since they can involve social, economic and medical aspects; however, information, acceptance and education are the keys for a successful new diet plan adherence. Therefore, a new relationship with food needs to be established and it may interfere not just in the patient’s diet, but also in those who are closest to him or her. Food restriction is a broad category that comprises changing the diet by selecting a type of food or avoiding typical allergens, such as: milk, soy, peanuts, wheat and eggs. The reason for the alimentary restriction varies and each condition follows specific protocols.
Gluten has gained special attention in the last few years and the demand for gluten free products has increased substantially [1]. Although gluten has become a very popular topic, there is a lot of confusion and a lack of education about Celiac Disease (CD), especially with regard to cross contamination. The most common misconception about CD is referring to it as a food allergy, which is often how it is seen by the general public.
CD is considered an immune mediated disorder that affects patients that have a genetic predisposition and it is triggered by the consumption of gluten [2]. It is also characterized by inflammation caused by leukocyte infiltration that changes the epithelial tissue in the small intestine [3].
Patients that are predisposed to the onset of CD carry the HLA-DQ2 and HLA DQ8 haplotype, which triggers the development of the pathology when in contact with gluten [4]. CD is also known as Celiac Sprue or Gluten-Sensitivity Enteropathy and is characterized by the malabsorption of nutrients due to intestinal epithelial tissue damage caused by immune response triggered by gluten. The enterocytes that form the lining of the small intestine are affected and damaged in the apical specialization of the columnar cells (villi), compromising the optical absorption of nutrients [2].
The small intestine is an extremely important organ in the digestive system since it is where most of the macro and micronutrients are absorbed. Any damage or dysfunction in the intestinal epithelium tissue can result in many nutrient deficiencies, compromising the functionality of other organs. Some of the non-gastrointestinal manifestations of CD are: osteoporosis, migraines, depression [8], dermatitis herpetiformis, type I diabetes mellitus, infertility, amenorrhea, adenocarcinoma, lymphomas [7], and thyroid problems.
Gluten is a protein found in rye, barley and wheat, which contains a peptide called gliadin; rich in glutamine and proline [6]. When gluten is consumed it is broken down into amino acids and peptides, where one of the resulting peptides is the 33 – amino acid alpha gliadin, which cannot be degraded by gastric, pancreatic and intestinal brush border protease enzymes, causing the immune response in the small intestine [2].
The 33 – amino acid alpha gliadin in contact with the lining epithelial tissue triggers a cascade of biochemical events that promote the tissue damage found in the CD. The figures 1 and 2 are illustrations of the mechanism of the CD.
When 33 –amino acid alpha gliadin reaches the intestinal epithelial tissue and makes contact with enterocytes cells, it promotes the release of IL-I5 in the intracellular environment, which stimulates the expression of CD8 lymphocytes [2]. Once CD8 lymphocytes are expressed, they also promote the formation of natural killer cells, known as NKG2D that attack the intestinal epithelium tissue causing damage to the enterocytes [2].
This first immune response mechanism shown above may allow other peptides of gliadin to cross the epithelium tissue and interact with other molecules, such as HLA-DQ2 and HLA-DQ8, which are involved in the mucosal damage found in CD.
Some of the gliadin that is able to cross the intestinal epithelium tissue undergoes a process called deamination, which is the loss of the amino group from the peptide. Gliadin has a strong affinity to the enzyme transglutaminase-2 (TG2) that converts the glutamine residues of the peptide gliadin into glutamic acid [3]. This change in polarity allows gliadin to bind with HLA-DQ2 or HLA-DQ8 receptors, which will activate T cells. As a result of this mechanism, cytokines are formed, and they are responsible for the mucosal damage in the intestinal epithelium tissue [2].
The HLA-DQ2 and HLA-DQ8 mechanism is one of the genetic components of CD, and recent medical literature has shown that CD involves complex genetic machinery. Therefore CD is characterized as a polygenetic immune based disorder [1].
The mucosal damage found in CD is not a food allergy pattern because food allergy by wheat or any other grain would not cause the severe damage in the epithelial tissue. Thus, CD cannot be referred to as a food allergy, a common mistake often made by the general public [6].
CD can manifest at any time in life and it is recommended that patients that suffer from gastrointestinal problems without direct cause and consume grains should be screened for CD [6].
The classic presentation of CD occurs when food-containing gluten is introduced in the child’s diet where symptoms, such as: irritability, abdomen distension, chronic diarrhea, and weight loss take place [2]. Also, nutrient deficiency, such as iron, is a common presentation [5][7].
In adults CD is often manifested between the ages of 30 and 40 [5][2], and chronic diarrhea, bloating and anemia are often linked [2]. Many of the cases of CD are not diagnosed because of the different presentations of the pathology; Silent CD is characterized by epithelial tissue damage and positive serology but no manifestation of the symptoms [2]; Latent CD is characterized by positive serology and no intestinal tissue damage [2].
Since CD can be in the asymptomatic form (Latent and Silent) it would be important to considerer the screening for CD as differential diagnosis in many other medical conditions [14]
Considering the different types of CD, (symptomatic, Silent and Latent), studies have shown the importance of screening relatives when a patient is diagnosed with CD [6][9]. In 2003 a medical study concluded that there is a high rate of CD in first and second-degree
Intestinal biopsy and specific blood tests are involved in the screening procedure for CD. When someone is under the diagnosis procedure, it is very important to continue consuming gluten until the biopsy and blood tests are done, since stopping the consumption of gluten at that moment can interfere in the test results. Once the diagnosis of CD is confirmed, a complete gluten free diet needs to take place.
The epidemiology of CD is a complex subject since many cases are not diagnosed because of the asymptomatic presentation of CD. According to Health Canada’s Position on Gluten free claims it was estimated that in June 2012, when the report was published, that 1% of the population of Canada was celiac, which would be approximately 340,000 Canadians at that time [10]. The Canadian Celiac Association predicts that 1 in 133 people in Canada has CD [11], and studies have shown that CD is a much more common condition worldwide [4][9].
The only treatment available for CD is a gluten free diet; and patients from any type of CD should avoid gluten completely [2][5][6]. A 5-year complete gluten free diet reduces the risk of developing cancer, which is one of the most dangerous complications of CD [6]. Untreated CD has a high risk of developing lymphomas; therefore a gluten free diet needs to be reached in order to reduce the risks at the level of the general public [14].
Medical literature has shown that a complete gluten free diet improves the gastrointestinal symptoms as well the extraintestinal manifestations when irreversible tissue damage is not achieved [14].
In order to support patients throughout the elimination process of gluten from the diet, information is a very important step. Every patient is one singular individual, and they will establish different relationships with the information that they have received.
Psychological aspects should be considered since the change in the diet may affect in the first moment social interactions and family dynamic with food. Medical nutrition and counselling are important aspects of the adherence of the lifelong gluten free diet.
Family education about a gluten free diet and gluten cross contamination should be considered. Cross contamination is characterized by the contamination of gluten free food with gluten particles.
In pediatric cases of CD, orientation of gluten cross contamination should be shared with the school and any other place where kids may have access to food.
Restriction to gluten does not mean social interaction restriction, and the understanding of the disease with information and its acceptance help a celiac patient to have a normal social life free of gluten.
A clear understanding of the role of the lifelong gluten free diet and the knowledge of the implications that a relapse to a gluten diet could have on their health are important aspects for a successful adherence of the gluten free environment.
The persistence of the gastrointestinal symptoms and extraintestinal manifestation in most of the cases are due to the relapse to a gluten diet or because of the implication of cross contamination of gluten in gluten free food [14].
In some cases when the gastrointestinal symptoms are not completely improved when a gluten free diet is incorporated the patient may have food sensitivity to other types of food. The most common food sensitivities, which also have shown to present villous atrophy are: milk protein, soy and eggs [14].
Another aspect to be considered is gluten cross reactivity which can be a variable involved when gastrointestinal symptoms persist after a gluten free diet has been introduced in celiac patients [15]. Some of the food linked to gluten cross reactivity are: oats, millet, corn, yeast and milk [15].
A gluten-free diet requires special attention, determination and acceptance. Many of the types of foods in a regular diet contain gluten, and many others are often contaminated with gluten when they are processed. Gluten free whole grains can become an unsafe product for celiac patients due to cross contamination during the transport, storage and milling processes [12].
Cross contamination is the most challenging aspect of a life without gluten, for most celiac patients a small amount of gluten such as 50ppm (parts per million) a day causes mucosal damage [14]. A study in 2007 found that even 10ppm (10mg/kg) of gluten a day had a negative effect in one of the patients that relapsed to epithelium damage [13].
Health Canada studied the exposure to gluten in the daily consumption of grains in different age groups and sexes, and they estimate that gluten levels cannot surpass 20ppm (20mg/kg) in labelled gluten free products. Since the rate of consumption varies from patient to patient, it would average out to be lower than 10ppm, making it safe for most celiac patients [10].
In order to illustrate how celiac patients are sensitive to gluten, since some of them cannot tolerate even 10mg/kg a day (10ppm), a simple slice of bread has approximately 1,600mg/kg of gluten [1].
Also, Health Canada has analyzed gluten free-labelled products that were sold in Canada in 2012, as mentioned in the Health Canada’s Position on Gluten free claims, and all of them had no gluten or less than 20ppm, therefore, being safe for most celiac patients [10].
Natural gluten free products that are not labeled gluten free may contain a superior value of gluten due to cross contamination and surpass the threshold that is estimated to be safe for celiac patients.
A study published in 2013, which analyzed 604 samples of natural gluten free flour and starch (not labeled gluten free) in 8 cities in Canada during 2010 and 2012, found that 61 samples presented gluten cross contamination [12]. The level of gluten exceeded the limit established of 20ppm of gluten, therefore turning the flour or starch unsafe for celiac patients [12].
Gluten free products also can be contaminated with gluten at home and special attention is required. If the kitchen is not a gluten free environment and it is shared with other gluten products, extra procedures should be considered. Kitchen utensils can carry traces of gluten and can contaminate the gluten free food.
A celiac patient needs to have a toaster and butter dish that is only for gluten free bread, and special labeled containers may be a great option in order to prevent cross contamination.
In order to assure a safe gluten free environment, many other tips can be found on the Canadian Celiac Association’s website[1] in the section of cross contamination.
Education regarding gluten contamination is very important. Many people do not know how celiac patients are sensitive to gluten and may not be careful with gluten traces when cooking a gluten free meal for celiac patients.
Once a life without gluten is established, a medical follow up should be done, since some vitamins can persist in a low level after a gluten free diet is incorporated, however supplementation is often recommended [14].
Medical literature has shown that some vitamins need to be administrated in the beginning of the treatment when CD is diagnosed and further follow up will determine if the patient needs to continue with the supplementation [14].
Common vitamin supplementation in the beginning of the treatment and follow up usually involves folic acid, vitamin B6 and B12, Magnesium, iron, L-cartinitine, vitamin A, E, K and D, copper and selenium [14].
For more information, visit a Naturopathic Doctor who has an extensive medical training in medical sciences and medical nutrition, and who is considered as a primary care physician in British Columbia, Canada.
References:
[1] Allen, P. J. (2015, June). Gluten-Related Disorder: Celiac Disease, Gluten Allergy, Non-Celiac Gluten Sensitivity. Pediatric Nursing, 41, 146-150
[2] Kumar, V., Abbas, A. K., Fausto, N., & Aster, J. C. (2015). Robins and Cotran Pathologic Basis of Disease (9th ed.). Philadelphia, PA: Sauders/Elsevier
[3] Pré, M. F., & Sollid, L. M. (2015). T-cell and B-cell immunity in celiac disease. Best Practice & Research Clinical Gastroenterology, 29(3), 413-423. doi:10.1016/j.bpg.2015.04.001
[4] Mishra, A., Prakash, S., Kaur, G., Sreenivas, V., Ahuja, V., Gupta, S. D., & Makharia, G. K. (2016). Prevalence of celiac disease among first-degree relatives of Indian celiac disease patients. Digestive and Liver Disease, 48(3), 255-259. doi:10.1016/j.dld.2015.11.007
[5] Fenoglio-Preiser, C. M., Noffsinger, A., Stemmermann, G. N., Lantz, P. E., & Isaacson, P. G. (2008). Gastrointestinal pathology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
[6] Yarnell, E. (2011). Natural approach to gastroenterology (Vol. II). Seattle: Healing Mountain Pub.
[7] Marz, R. B. (1999). Medical nutrition from Marz: (a textbook in clinical nutrition). Portland, Or.: Omni-Press.
[8] Hollon, J. R., Cureton, P. A., Martin, M. L., Puppa, E. L., & Fasano, A. (2013). Trace gluten contamination may play a role in mucosal and clinical recovery in a subgroup of diet-adherent non-responsive celiac disease patients. BMC Gastroenterol BMC Gastroenterology, 13(1). doi:10.1186/1471-230x-13-40
[9] Fasano, A., Berti, I., Gerarduzzi, T., Not, T., Colletti, R. B., Drago, S., . . . Horvath, K. (2003). Prevalence of Celiac Disease in At-Risk and Not-At-Risk Groups in the United States. Arch Intern Med Archives of Internal Medicine, 163(3), 286. doi:10.1001/archinte.163.3.286
[10] Government of Canada – Health Canada [internet] 2012 [Cited 2016 March 31]. Health Canada’s Position on Gluten Free Claims. Retrieved on 2016 March 28 from http://www.hc-sc.gc.ca/fn-an/alt_formats/pdf/securit/allerg/cel-coe/gluten-position-eng.pdf
[11] Canadian Celiac Association. [Internet] s/d. [Cited 2016 March 26]. Cross contamination. Retrieved on 2016 March 26 from http://www.celiac.ca/?page_id=882
[12] Koerner, T., B., et al. (2013). Gluten Contamination of Naturally Gluten-free Flours and Starches Used By Canadians with Celiac Disease. Food additives & Contaminants: Part A, (30/12), 2017-2021
[13] Catassi, C., et al. (2007) A Prospective, Double-blind, Placebo-Controlled Trial to Establish a Safe Gluten Threshold for Patients with Celiac Disease. American Clinical Nutrition, 85, 160-166
[14] Gaby, A. (2011). Nutritional medicine. Concord: Fritz Perlberg.
[15] Vojdani, A., & Tarash, I. (2013). Cross-Reaction between Gliadin and Different Food and Tissue Antigens. FNS Food and Nutrition Sciences, 04(01), 20-32. doi:10.4236/fns.2013.41005
