Gluten-free diet

Wheat

A gluten-free diet (GFD) is a diet that excludes gluten, a protein composite found in wheat, barley, rye,^[1][2] and all their species and hybrids (such as spelt,^[1] kamut, and triticale^[1][2]). The inclusion of oats in a gluten-free diet remains controversial. Avenin present in oats may also be toxic for coeliac people;^[2] its toxicity depends on the cultivar consumed.^[3] Furthermore, oats are frequently cross-contaminated with cereals containing gluten.^[2]

Gluten causes health problems for those with gluten-related disorders, including coeliac disease (CD), non-coeliac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy.^[4] In these patients, the gluten-free diet is demonstrated as an effective treatment.^[5][6][7] In addition, at least in some cases, the gluten-free diet may improve gastrointestinal and/or systemic symptoms in diseases like irritable bowel syndrome, rheumatoid arthritis, multiple sclerosis or HIV enteropathy, among others.^[8]

Gluten proteins have low nutritional and biological value, and the grains that contain gluten are not essential in the human diet.^[9] However, an unbalanced selection of food and an incorrect choice of gluten-free replacement products may lead to nutritional deficiencies. Replacing flour from wheat or other gluten-containing cereals with gluten-free flours in commercial products may lead to a lower intake of important nutrients, such as iron and B vitamins. Some gluten-free commercial replacement products are not enriched or fortified as their gluten-containing counterparts, and often have greater lipid / carbohydrate content. Children especially often over-consume these products, such as snacks and biscuits. Nutritional complications can be prevented by a correct dietary education.^[2]

A gluten-free diet should be mainly based on naturally gluten-free foods with a good balance of micro and macro nutrients: meat, fish, eggs, legumes, nuts, fruits, vegetables, potatoes, rice, and maize are all appropriate. If commercially-prepared, gluten-free replacement products are used, it is preferable to choose those that are enriched or fortified with vitamins and minerals.^[2] Furthermore, healthy alternatives to these products are pseudocereals (quinoa, amaranth, and buckwheat) and other minor cereals, which have high biological and nutritional value.^[2][9]

Rationale behind adoption of the diet

One breadcrumb of this size contains enough gluten to cause significant digestive discomfort in people with gluten-related disorders when they are following a gluten-free diet. Consuming gluten even in small quantities, which may be the result of inadvertent cross-contamination, causes active immune response and carries the risk of triggering associated diseases.^{[10][11][12][13][14]}

Coeliac disease

Coeliac disease (American English: celiac) (CD) is a chronic, immune-mediated, and mainly intestinal process, caused by the ingestion of wheat, barley, rye and derivatives, that appears in genetically predisposed people of all ages. CD is not only a gastrointestinal disease, because it may affect several organs and cause an extensive variety of non-gastrointestinal symptoms, and most importantly, it may often be completely asymptomatic. Added difficulties for diagnosis are the fact that serological markers (anti-tissue transglutaminase [TG2]) are not always present^[15] and many patients may have minor mucosal lesions, without atrophy of the intestinal villi.^[16]

CD affects approximately 1-2% of general population all over the world^[17] and is on increase,^[18] but most cases remain unrecognized, undiagnosed and untreated, and exposed to the risk of long-term complications.^[19][20] Patients may suffer severe disease symptoms and be subjected to extensive investigations for many years, before a proper diagnosis is achieved.^[21] Untreated CD may cause malabsorption, reduced quality of life, iron deficiency, osteoporosis, obstetric complications (stillbirth, intrauterine growth restriction, preterm birth, low birthweight, and small for gestational age),^[22] an increased risk of intestinal lymphomas and greater mortality.^[23] CD is associated with some autoimmune diseases, such as diabetes mellitus type 1, thyroiditis,^[24] gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and more.^[24]

CD with “classic symptoms”, which include gastrointestinal manifestations such as chronic diarrhoea and abdominal distention, malabsorption, loss of appetite, and impaired growth, is currently the least common presentation form of the disease and affects predominantly to small children generally younger than two years of age.^[19][21]

CD with “non-classic symptoms” is the most common clinical found type^[21] and occurs in older children (over 2 years old),^[21] adolescents and adults.^[21] It is characterized by milder or even absent gastrointestinal symptoms and a wide spectrum of non-intestinal manifestations that can involve any organ of the body, and very frequently may be completely asymptomatic^[19] both in children (at least in 43% of the cases^[25]) and adults.^[19]

Following a lifelong gluten-free diet is the only medically-accepted treatment for people with coeliac disease.^[9][26]

Non-coeliac gluten sensitivity

Non-coeliac gluten sensitivity (NCGS) is described as a condition of multiple symptoms that improves when switching to a gluten-free diet, after coeliac disease and wheat allergy are excluded.^[27][28] Patients may develop gastrointestinal symptoms, which resemble those of irritable bowel syndrome (IBS)^[29][30] and/or a variety of nongastrointestinal symptoms.^[12][31][32]

Gastrointestinal symptoms may include any of the following: abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation),^[12][32] nausea, aerophagia, gastroesophageal reflux disease, and aphthous stomatitis.^[31][32] A range of extra-intestinal symptoms, said to be the only manifestation of NCGS in the absence of gastrointestinal symptoms,^[12][31][32] have been suggested, but remain controversial.^[23][33] These include: headache, migraine, "foggy mind", fatigue, fibromyalgia,^[33][34] joint and muscle pain, leg or arm numbness, tingling of the extremities, dermatitis (eczema or skin rash), atopic disorders such as asthma, rhinitis, other allergies, depression, anxiety, iron-deficiency anemia, folate deficiency or autoimmune diseases.^{[12][31][32][33]} NCGS has also been controversially implicated in some neuropsychiatric disorders, including schizophrenia, eating disorders, autism, peripheral neuropathy, ataxia and attention deficit hyperactivity disorder (ADHD).^{[12][23][31][32][33]} Above 20% of people with NCGS have IgE-mediated allergy to one or more inhalants, foods or metals, among which most common are mites, graminaceae, parietaria, cat or dog hair, shellfish and nickel.^[12] Approximately, 35% of patients suffer other food intolerances, mainly lactose intolerance.^[33]

The pathogenesis of NCGS is not yet well understood. It was hypothesized that gluten, like occurs in coeliac disease, is the cause of NCGS.^[31] Much recent research on NCGS has aimed at determining which agents trigger a response in NCGS patients: to which extent gluten, FODMAPs, ATIs (plant-derived proteins present in glutencontaining cereals and gluten) or wheat germ agglutinin are involved.^[32][33] For these reasons, NCGS is a controversial syndrome^[35] and some authors still question it.^[36] In a 2013 double-blind placebo-controlled trial (DBPC) by Biesiekierski et al. in a few patients with irritable bowel syndrome (IBS), the authors found no difference between gluten or placebo groups and the concept of NCGS as a syndrome was questioned. Nevertheless, this study seems to have design errors and an incorrect selection of participants, which could have masked the true effect of gluten reintroduction.^[20][33] In a review of May 2015 published in Gastroenterology, Fasano et al. conclude that besides gluten, ATIs and FODMAPs present in gluten, wheat, barley, rye, and their derivatives play a role in the development of NCGS symptoms. ATIs, which resist proteolytic digestion, may be the inducers of innate immunity in people with coeliac disease or NCGS. FODMAPs cause mild wheat intolerance at most, which is mainly limited to gastrointestinal symptoms.^[31]

After exclusion of coeliac disease and wheat allergy,^[37] the subsequent step for diagnosis and treatment of NCGS is to start a strict gluten-free diet to assess if symptoms improve or resolve completely. This may occur within days to weeks of starting a GFD, but improvement may also be due to a non-specific, placebo response.^[38] Recommendations may resemble those for coeliac disease, for the diet to be strict and maintained, with no transgression.^[12] The degree of gluten cross contamination tolerated by people with NCGS is not clear but there is some evidence that they can present with symptoms even after consumption of small amounts.^[12] It is not yet known whether NCGS is a permanent or a transient condition.^[12][35] A trial of gluten reintroduction to observe any reaction after 1–2 years of strict gluten-free diet might be performed.^[12]

A subgroup of NCGS patients may not improve by eating commercially available gluten-free products, which are usually rich of preservatives and additives, because chemical additives (such as sulphites, glutamates, nitrates and benzoates) might have a role in evoking functional gastrointestinal symptoms of NCGS. These patients may benefit from a diet with a low content of preservatives and additives.^[39]

NCGS, which is possibly immune-mediated, now appears to be more common than coeliac disease,^[40] with prevalence rates between 0.5–13% in the general population.^[41]

Wheat allergy

People can also experience adverse effects of wheat as result of a wheat allergy.^[20] Gastrointestinal symptoms of wheat allergy are similar to those of coeliac disease and non-coeliac gluten sensitivity, but there is a different interval between exposure to wheat and onset of symptoms. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and could be anaphylaxis.^[15][42]

The treatment of wheat allergy consists of complete withdrawal of any food containing wheat and other gluten-containing cereals.^[6][42] Nevertheless, some patients can tolerate barley, rye or oats.^[43]

As a fad diet

A gluten free artisan bakery in Upper Street, Islington, London.

Gluten-free fad diets are endorsed by celebrities such as Miley Cyrus^[44] and are used by some world class athletes who believe the diet can improve energy and health.^[45] The book Wheat Belly which refers to wheat as a "chronic poison" became a New York Times bestseller within a month of publication in 2011.^[46] People buy gluten-free food "because they think it will help them lose weight, because they seem to feel better or because they mistakenly believe they are sensitive to gluten."^[47] It should not be undertaken to diagnose one's own symptoms,^[48] because tests for coeliac disease are reliable only if the patient has been consuming gluten.

Although popularly used as an alternative treatment for people with autism, there is no good evidence that a gluten-free diet is of benefit in treating the symptoms of autism.^[49][50][51]

This diet adds a financial burden to those who think they can solve their health issues by cutting gluten out of their diet. There is a consensus in the medical community that people should consult a physician before going on a gluten-free diet, so that a medical professional can accurately test for coeliac disease or any other gluten-induced health issues.^[52]

In a review of May 2015 published in Gastroenterology, Fasano et al. conclude that, although there is an evident "fad component" to the recent rise in popularity of the gluten-free diet, there is also growing and unquestionable evidence of the existence of non-coeliac gluten sensitivity.^[53]

Eating gluten-free

Quinoa is a pseudocereal that is gluten-free.

Rice bread

Gluten-free bread made of a mixture of flours like buckwheat flour, tapioca flour, millet flour and psyllium seed husks. Special flour mixes can be bought for bread-making purposes

The diet is primarily an elimination diet focused on avoiding foods containing gluten, such as wheat, rye, barley, triticale, kamut, malt,^[54] and foods that may include them, or shared transportation or processing facilities with them.^[54] Some cereal grains, although gluten-free in themselves, may contain gluten by cross-contamination during processing steps or transport; this includes oats.^[55] Some processed foods may contain gluten, so they would need specific labeling, such as gluten-free ice-cream, ketchup, chicken bouillon, corn cereal, ice cream toppings, malt flavoring, and chocolate.

Cross contamination in the home is also a consideration for those who suffer gluten-related disorders.^[14][56] There can be many sources of cross contamination, as for example when family members prepare gluten-free and gluten-containing foods on the same surfaces (counter tops, tables, etc.) or share utensils that have not been cleaned after being used to prepare gluten-containing foods (cutting boards, colanders, cutlery, etc.), kitchen equipment (toaster, cupboards, etc.) or certain packaged foods (butter, peanut butter, etc.).^[56]

Medications and dietary supplements are made using excipients that may contain gluten.^[57]

The gluten-free diet includes naturally gluten-free food, such as meat, fish, seafood, nuts, legumes, fruit, vegetables, potatoes, pseudocereals (in particular amaranth, buckwheat, chia seed, quinoa), only certain cereal grains (corn, rice, sorghum), minor cereals (including fonio, Job's tears, millet, teff, called "minor" cereals as they are "less common and are only grown in a few small regions of the world"),^[54] some other plant products (arrowroot, mesquite flour,^[58] sago,^[59] tapioca^[59]) and products made from these gluten-free foods.

Risks

Unless great care is taken, a gluten-free diet can lack the vitamins, minerals, and fiber which are found in wheat, barley, rye, kamut, and other gluten-containing whole grains^[60] and may be too high in fat and calories.^[58][61] Processed gluten-free foods are often higher in salt, sugar, glycemic index, transfats and other processed fats.^[58] Although the lack of vitamins, minerals, and fiber can be mitigated through the consumption of brown rice and quinoa,^[62] many practitioners of the diet do not consume the recommended number of grain servings per day.^[63][64] Many gluten-free products are not fortified or enriched by such nutrients as folate, iron, and fiber as traditional breads and cereals have been during the last century.^[65] Advances towards higher nutrition-content gluten-free bakery products, improved for example in terms of fiber content and glycemic index, have been made by using not exclusively corn starch or other starches to substitute for flour. In this aim, for example the dietary fiber inulin (which acts as a prebiotic^[66]) or quinoa or amaranth wholemeal have been as substitute for part of the flour. Such substitution has been found to also yield improved crust and texture of bread.^[67]

The inclusion of oats in gluten-free diet remains controversial.^[2] Its toxicity depends on the oat cultivar consumed because of prolamin genes, protein amino acid sequences, and the immunoreactivities of toxic prolamins which are different among oat varieties.^[2][3] Some cultivars of oat could be a safe part of a gluten-free diet, requiring an accurate knowledge of the oat variety used.^[3] Oat products may also be cross-contaminated with gluten-containing cereals.^[2][3] The long-term effects of pure oats consumption are still unclear. Coeliac people who choose to consume oats need a more rigorous lifelong follow-up, whom include periodic performance of intestinal biopsies.^[68]

Up to 30% of people with known coeliac disease often continue having or redeveloping symptoms.^[56][69] Also, a lack of symptoms and/or negative blood antibodies levels are not reliable indicators of intestinal recuperation. Several studies show an incomplete recovery of small bowel despite a strict gluten-free diet, and about 79% of the treated patients have persistent villous atrophy.^[56] This lack of recovery is mainly caused by inadvertent exposure to gluten.^[56][69] People with poor basic education and understanding of gluten-free diet often believe that they are strictly following the diet, but are making regular errors.^[13][56] In addition, some people often deliberately continue eating gluten because of limited availability, inferior taste, higher price, and inadequate labelling of gluten-free products. Poor compliance with the regimen is also influenced by age at diagnosis (adolescents), ignorance of the consequences of the lack of a strict treatment and certain psychological factors.^[56] Ongoing gluten intake can cause severe disease complications, such as various types of cancers (both intestinal and extra-intestinal) and osteoporosis.^[56][69]

Regulation and labels

The term gluten-free is generally used to indicate a supposed harmless level of gluten rather than a complete absence.^[11] The exact level at which gluten is harmless is uncertain and controversial. A 2008 systematic review tentatively concluded that consumption of less than 10 mg (10 ppm) of gluten per day is unlikely to cause histological abnormalities, although it noted that few reliable studies had been done.^[11]

Regulation of the label gluten-free varies by country. Most countries derive key provisions of their gluten-free labeling regulations from the Codex Alimentarius international standards for food labeling as a standard relating to the labeling of products as gluten-free. It only applies to foods that would normally contain gluten.^[70] Gluten-free is defined as 20 ppm (= 20 mg/kg) or less. It categorizes gluten-free food as:

• Food that is gluten-free by composition
• Food that has become gluten-free through special processing.
• Reduced gluten content, food which includes food products with between 20 and 100 ppm of gluten. Reduced gluten content is left up to individual nations to more specifically define.

The Codex Standard suggests the enzyme-linked Immunoassay (ELISA) R5 Mendez method for indicating the presence of gluten, but allows for other relevant methods, such as DNA. The Codex Standard specifies that the gluten-free claim must appear in the immediate proximity of the name of the product, to ensure visibility.

There is no general agreement on the analytical method used to measure gluten in ingredients and food products.^[71] The ELISA method was designed to detect w-gliadins, but it suffered from the setback that it lacked sensitivity for barley prolamins.^[72] The use of highly sensitive assays is mandatory to certify gluten-free food products. The European Union, World Health Organization, and Codex Alimentarius require reliable measurement of the wheat prolamins, gliadins rather than all-wheat proteins.^[73]

Australia

The Australian government recommends^[74] that:

• food labeled gluten-free include no detectable gluten (<3ppm ^[75]) oats or their products, cereals containing gluten that have been malted or their products
• food labeled low gluten claims such that the level of 20 mg gluten per 100 g of the food

Brazil

All food products must be clearly labelled whether they contain gluten or they are gluten-free.^[76]

Canada

Health Canada considers that foods containing levels of gluten not exceeding 20 ppm as a result of contamination, meet the health and safety intent of section B.24.018 of the Food and Drug Regulations when a gluten-free claim is made.^[77] Any intentionally added gluten, even at low levels must be declared on the packaging and a gluten-free claim would be considered false and misleading. Labels for all food products sold in Canada must clearly identify the presence of gluten if it is present at a level greater than 10 ppm.^[78]

European Union

The EU European Commission delineates^[79] the categories as:

• gluten-free: 20 ppm or less of gluten
• very low gluten foodstuffs: 20-100ppm gluten.

All foods containing gluten as an ingredient must be labelled accordingly as gluten is defined as one of the 14 recognised EU allergens.^[80]

United States

Until 2013 anyone could use the gluten-free claim with no repercussion. In 2008, Wellshire Farms chicken nuggets labeled gluten-free were purchased and samples were sent to a food allergy laboratory^[81] where they were found to contain gluten. After this was reported in the Chicago Tribune, the products continued to be sold. The manufacturer has since replaced the batter used in its chicken nuggets.^[82] The U.S. first addressed gluten-free labeling in the 2004 Food Allergen Labeling and Consumer Protection Act (FALCPA). The Alcohol and Tobacco Tax and Trade Bureau published interim rules and proposed mandatory labeling for alcoholic products in 2006.^[83] The FDA issued their Final Rule on August 5, 2013.^[84] When a food producer voluntarily chooses to use a gluten-free claim for a product, the food bearing the claim in its labeling may not contain:

• an ingredient that is a gluten-containing grain
• an ingredient that is derived from a gluten-containing grain that has not been processed to remove gluten
• an ingredient that is derived from a gluten-containing grain, that has been processed to remove gluten but results in the presence of 20 ppm or more gluten in the food. Any food product claiming to be gluten-free and also bearing the term "wheat" in its ingredient list or in a separate "Contains wheat" statement, must also include the language "*the wheat has been processed to allow this food to meet the FDA requirements for gluten-free foods," in close proximity to the ingredient statement.

Any food product that inherently does not contain gluten may use a gluten-free label where any unavoidable presence of gluten in the food bearing the claim in its labeling is below 20 ppm gluten.

See also

• Gluten-free, casein-free diet
• Specific Carbohydrate Diet
• Paleolithic diet

References

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