Gluten sensitivity

Gluten sensitivity (GS) belongs to a spectrum of disorders in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in coeliac disease or wheat allergy (other conditions which fall under the gluten-related disorders spectrum).

Gluten sensitivity is thought to affect approximately 6% of the general population.[1] Symptoms of gluten sensitivity include bloating, abdominal discomfort, pain or diarrhea; or it may present with a variety of extraintestinal symptoms including headaches and migraines, lethargy and tiredness, attention-deficit disorder and hyperactivity, autism and schizophrenia, muscular disturbances as well as bone and joint pain.[2] [3] [4] [5] [6]

Until recently, the terms gluten sensitivity and coeliac disease were used interchangeably in literature. However, emerging research is beginning to identify the differences that exist between coeliac disease and gluten sensitivity. If the medical history of a patient, along with clinical tests, rule out coeliac disease and wheat allergy, a diagnosis of gluten sensitivity can be considered. However, certain criteria need to be met before a diagnosis of gluten sensitivity can be confirmed (see diagnosis section). Treatment for all three conditions is a gluten-free diet; the difference being that with wheat allergy the interruption is temporary and drugs may be administered; in the case of coeliac disease the diet is lifelong and even ingesting very small amounts of gluten-containing food could damage their health and, in the case of gluten sensitivity the withdrawal of gluten from the diet may only be temporary.

Gluten is a protein composite found in foods processed from wheat and related species, including barley and rye. It gives elasticity to dough helping it to rise and to keep its shape. It is found in many staple foods in the Western diet. Gluten is composed of a gliadin fraction (alcohol soluble) and a glutenin fraction (only soluble in dilute acids or alkali).

Contents

Symptoms

Symptoms of gluten sensitivity may include bloating, abdominal discomfort, pain, or diarrhea; or it may present with a variety of extraintestinal symptoms including headaches and migraines, lethargy and tiredness, attention-deficit disorder and hyperactivity, autism and schizophrenia, muscular disturbances as well as bone and joint pain.[7] [8] [9] [10]

Diagnosis of Gluten Sensitivity

If the medical history of a patient, along with clinical tests, rule out coeliac disease and wheat allergy, a diagnosis of gluten sensitivity can be considered. However, before a diagnosis of gluten sensitivity can be confirmed the following criteria need to be met:

If the above criteria are met then the person can be classed as ‘gluten sensitive’ and it can be treated with a gluten-free diet for a period of time. This should lead to symptom resolution.

A diagnostic algorithm for gluten sensitivity has been proposed:

Difference between gluten sensitivity and coeliac disease

Whilst the research surrounding gluten sensitivity is still very much emerging, coeliac disease is a well-defined condition. It is a lifelong autoimmune condition characterised by the chronic inflammation of the intestine. In genetically-predisposed children and adults the intake of foods containing gluten leads to an immune response in the small intestine. This results in the flattening of the intestinal villi and in reduced absorption of nutrients from food which can lead to nutritional deficiencies and associated long-term complications such as osteoporosis. It is believed coeliac disease affects 1% of the general population in the Western world.

In comparison, in a recent clinical paper, gluten sensitivity was defined as ‘one or more of a variety of immunological, morphological or symptomatic manifestations that may also be shared by coeliac disease and irritable bowel syndrome (IBS) [11]. In cases where there is reactivity to gluten, yet coeliac disease and wheat allergy are eliminated as possibilities, gluten sensitivity may be considered. Whilst the general clinical picture for gluten sensitivity is similar to coeliac disease in particular, it is usually less severe and neither anti-tissue transglutaminase antibodies nor autoimmune comorbidities are found.

It is believed that approximately 40-50% of gluten sensitivity patients may have IgG or IgA anti-gliadin antibodies (AGA)[12] [13] There is also a study identifying approximately 50% of gluten sensitivity patients, few more than the general population, carry either HLA DQ 2 or 8 [14]

On closer inspection, it has also been found that gluten-sensitive subjects do not develop full histological lesions; their lesions, if any, are limited to types 0-1 of the Marsh classification. In addition, it has been found that they have normal intestinal permeability and an increased expression of Toll Like receptors 2 (TLR2) but no change in the cytokines involved in adaptive immune responses Th1 and Th17 such as IL-6, IL-17 A, IL 21, which are increased only in patients with coeliac disease. The knowledge of the response in gluten sensitivity to date suggests that only the innate immune system is involved, whereas coeliac disease is an adaptive immune response (autoimmunity).

Gluten sensitivity should have a defined cause, although not apparent always with first examination, affected individuals should eventually fall into GSE or wheat allergy. Only rarely should gluten sensitivity be idiopathic. Idiopathic gluten sensitivity (IGS) arises spontaneously or from an obscure or unknown cause and may involve neuropathy, myopathy, dermal, or intestinal abnormalities. Anti-gliadin antibodies are the primary link between gluten and idiopathic sensitivity in instances "in which enteropathy or allergy are not clearly involved". [15] This form of gluten sensitivity is controversial at the moment but there is a growing body of research to support the concept of gluten sensitivity that is different from coeliac disease and wheat allergy.

Etiology

Gluten sensitivity can develop at any point in life, and symptomatic disease may appear years after disease develops. When enteropathy develops in early childhood symptomatic disease is more rapidly evident. A survey of geriatrics with coeliac disease in Finland[16] revealed that the incidence of disease was much higher than the general population. Allergic disease may rise or fall with age; however, certain evidence points to the increased or daily use of non-steroidal anti-inflammatory factors (aspirin, ibuprofen) as an increased risk factor for urticaria or anaphylaxis, and the sensitizing dose may include low-dose aspirin therapy used in the treatment of heart disease. Idiopathic disease appears largely late onset.

Gluten-sensitive enteropathy develops as a consequence of genetic and environmental factors. Other than the involvement of certain HLA-DQ isoforms (antigen presenting proteins in humans) and certain wheat proteins, there is no clarity in the involvement of other genes or other environmental factors (see risk modifiers). Strong genetic factors such as seen in GSE have not been seen in gluten allergy, and with idiopathic gluten-sensitivity the HLA-DQ associations are weak.

Researchers reported extreme fatigue and pain in patients without celiac disease, with gliadin antibodies. They called this a “non-celiac gluten intolerance” for which there is no explanation as to the mechanisms involved.[17]

Causes of gluten sensitivity

Underlying conditions
The normal intestine
Wheat proteins interact with the immune system by means of DQ2-mediated programmed cell death (apoptosis) of the gut in sensitive individuals. New research is finding that the coeliac gut may be predisposed to sensitivity in the absence of HLA genetic factors.
How diet proteins reach the blood
In the normal gut, proteins are digested to peptides by pepsin (stomach), trypsin and chymotrypsin (derived from the pancreas and activated in the gut). Peptides are further digested when they enter the villi, where brush border peptidase break proteins into amino acids. Over much of the small intestine only small solutes, like water, can cross the tight junctions, however some regions of the intestine peptides as large as 500 daltons (4 amino-acids residues in length can cross).
The gluten sensitive gut

There is a growing body of evidence that the gluten-sensitive intestine differs from the normal gut. Several gluten peptides can infiltrate the region behind the cells lining the small intestine. The "33mer" of α-2 gliadin is a magnitude larger than the maximum size allowable by the barrier around the cell, the tight junctions. Omega-5 gliadin peptides have been found in the blood stream of people with exercise-induced anaphylaxis, aided by salicylates. And the innate "25mer" is capable of reaching mononuclear cells in coeliac gut, but in normal gut is broken down by brush border peptidases. It may be a lower peptidase activity that explains the presence of these peptides behind the brush border membrane. Recently, it was found that an α-9 gliadin peptide was capable of binding the "CXCR3" receptor, increasing zonulin production and weakening tight junctions, this may explain how, generally, larger peptides can enter the gluten-sensitive gut.

Triticeae and the potential role of selective evolution in gluten sensitivities

The fruiting bodies of plants contain genes as well as reserves of nutrients that allow seedlings to grow. The enrichment of nutrients is an attractant to herbivores and omnivores. For annual grasses that release seeds during a brief period each year there is a need to protect seeds during maturation from insects or animals, which might stock seeds for year round usage. For wheat, alpha-gliadins are seed-storage proteins, but also act as inhibitors of alpha-amylase activity in some animals, particularly in insects.[18] It is also known that wheat gliadins create intestinal disease when fed to very young rodents.[19] One recent publication even raises the question 'is wheat safe for anyone to eat?'.[20] Critically, pathology in insects or artificially fed rodents does not reflect what causes disease in humans, but it is interesting that toxicological effects of wheat are being uncovered that do have the potential to cause pathology in humans. One interesting consequence of these studies is that there may be a general gluten sensitivity that underlies various pathological manifestations, such as coeliac disease, urticaria and idiopathic sensitivity.

The rise of gluten sensitivity (particularly in adults) may reflect the convergence of many phenomena. An aging population, genetic risks associated with westernization, excesses in the diet, sensitizing chemicals (e.g.NSAIDs), and allergy-enhancing chemical treatment of foods (e.g. enzymatic deamidation of gluten) may act together with natural defensive agents in foods to cross the threshold between normality and pathology.

Gluten toxicity

An increasing number of studies on gliadin indicate gluten has a direct and modifying effect on the cells of the small intestine. Two different lines of research show that different gliadins can increase permeability of the epithelial cells (outermost cells of the villus) allowing food proteins to enter. One study examined the effect of ω-5 gliadin, the primary cause of exercise/aspirin induced anaphylaxis, and found increased permeability of intestinal cells caused by this gliadin and another wheat albumin.[21] Another line of research shows gliadin binds a chemoattractant receptor and causes increases of a factor that destroys tight junctions.[22] These junctions prevent leakage around the cells that line the small intestine, resulting in the leaking of food proteins into the body.[23] These toxicities of gluten that are not part of the adaptive immune response may be the link between wheat and gluten sensitivity, and possibly type 1 diabetes.

Further information: Innate immunity of gluten

Immunochemistry of glutens

Main article: Gluten immunochemistry

Triticeae glutens are important factors in several inflammatory diseases. The immunochemistry can be subdivided into innate responses (direct stimulation of immune system), class II mediated presentation (HLA DQ), class I mediated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In enteropathy, there are at least 3 types of recognition, innate immunity (a form of cellular immunity priming), HLA-DQ and antibody recognition of gliadin and transglutaminase.[24] The three dominant sequences responsible for the antibody reaction have been identified.[25][26] With idiopathic disease only antibody recognition to gliadin has been resolved. In wheat allergy, there appears to be an innate components and the response pathways are mediated through IgE against gliadin and other wheat proteins.[27][28][29]

Separating forms of gluten sensitivity

Only rarely should gluten sensitivity be without cause. Generally the sensitivity can be split between coeliac disease, gluten sensitivity and wheat allergy. Since individuals with coeliac disease can also have wheat allergy, a finding of wheat allergy does not eliminate the possibility of enteropathy. Individuals highly suspect of coeliac disease may be tested for anti-transglutaminase antibodies followed by duodenal biopsy, this will confirm or refute active coeliac disease.[30] The study that recommends this, however, has a number of ATA positive/biopsy-negative individuals, this could result from patchy villous atrophy or subclinical pathology.[31][32] One current study recommended at biopsy samples running distally from the duodenum to avoid the risk of false negatives. Eliminating the possibility of coeliac disease can generally be done by adding HLA-DQ typing, in which DQ2 and DQ8 are found in enteropathy 98% of the time in caucasians, DQ7.5 the remaining 1.6% and 0.4% not found with either of these 3. Without ATA or HLA-DQ2/8 positivity, coeliac disease is not likely the cause of the sensitivity. In either case, other avenues of diagnostics, such as allergy testing are available.[33] Rarely gluten sensitivity may be idiopathic, a potential that wheat proteins play a role in other disease, in these instances DQ1 may be associated with sensitivity. There is research showing that in certain patients with gluten ataxia early diagnosis and treatment with a GFD can improve ataxia and prevent its progression. [34] Recently, a classification of gluten-related disorders has been proposed:

Gluten-sensitive enteropathy

Main article: Coeliac disease (CD)

Coeliac disease as the classically defined gluten-sensitivity and dermatitis herpetiformis was appended to a broadening definition of gluten sensitivity. The diagnostic "gold standard" of coeliac disease is the villus atrophy detected in duodenal biopsies. However, it is now recognized that inflammation of the epithelial tissue of the small intestine precedes atrophy. Early in the disease, gluten elicits T-lymphocyte recognition of gluten hydrolysates (polypeptides of gluten) and gluten peptides bind to mammalian tissue transglutaminase (tTG). This second interaction results in the production of "self" antibodies to tTG. This increases lymphocytes within the epithelia of the small intestine (Marsh grade 1 and 2) and antibody-tTG complexes seen as deposits. This usually progresses to coeliac disease (Marsh grade 3 and 4). The dietary cause of GSE is not limited to wheat gluten; 'glutens' from all known edible cultivars of Triticeae can induce GSE in susceptible individuals (see: Gluten immunochemistry).

Frequencies of phenotypes in Coeliac disease, Normal Americans, Odds ratios
DQ haplotypes -Celiac Disease
DQ hap 2.5 2.2 7.5 8.0 Other
2.5 34 22 4.0 2.0 22
2.2 1.1 4.0 1.1 2.9
7.5 0.3 0.0 1.3
8.1 2.9 2.0
other 0.4
DQ haplotypes -Normal Population
DQ hap 2.5 2.2 7.5 8.1 Other
2.5 1.7 2.9 2.9 1.8 15.1
2.2 1.2 2.4 1.6 12.8
7.5 1.2 1.5 1.3
8.1 0.5 8.0
other 33.4
Odds ratios
DQ hap 2.5 2.2 7.5 8.1 Other
2.5 20:11 8:12 1.4:16 1.1:1 1.5:15
2.2 1:1.1 1.6:14 1:1.3 1:5
7.5 1:4 0 1:10
8.1 6:13 1:4
other 1:100
DQ Types by allele numbers (e.g. 0501) can be found here
Main article: Associated Conditions

There are a large number of medical conditions that result from GSE that can occur prior to the development of coeliac disease and might be gluten responsive. While the level of villus atrophy in some cases of GSE may not reach clinical coeliac disease recognition, the elevation of cellular immunity is capable of producing disorders more frequently found in coeliac disease. Conditions secondary to GSE are important diagnostic criteria for gluten sensitivity when there may be no obvious intestinal abnormality. Presentation of GSE is often the result of initial recognition of the secondary condition which in followup testing (ATA test, AGA test, HLA-DQ typing, and/or biopsy) recognizes the primary condition. The secondary conditions associated with GSE tend to make late onset coeliac disease a systemic phenomena.

Idiopathic gluten sensitivity

Idiopathic diseases are proposed as an expansion of the gluten-sensitivity. By the definition of idiopathic disease, the cause is not well defined. One hundred years ago, before gluten was discovered as the cause of coeliac disease, coeliac disease in adults was called adult idiopathic steatorrhoea, non-tropical sprue, sprue nostras, and many other names. The debate over this subset stems from the fact that identification of all grades of GSE and allergies is not uniformly approached. Most cases of early GSE go undetected, particularly before 2005. There appears to be a small fraction of non-GSE gluten-sensitive individuals that show neither gluten-allergies but do have elevated anti-gliadin IgA or IgG. Common symptoms are peripheral neuropathies and cerebral ataxia. Within the GSE set these may be explained by calcification of brain channels and avitaminosis. Within the remaining 'DQ2 and DQ8'less cohort. Given that this cohort of GS is idiopathic, the role of allergies, other sensitivities (e.g. aspirin), or other factors in IGS is also unresolved.

Further information: Anti-gliadin antibodies

Silent Disease. Depending on testing somewhere between 3 and 15% of the normal population have anti-gliadin antibodies (AGA). Studies using anti-gliadin antibodies (AGA) reveal that in undiagnosed or untreated individuals with AGA, with increasing risk for lymphoid cancers and decreased risk for other associated with affluence.[35] Though it is unknown in these studies the percentage that are early stage GSE.

Neuropathies

Main article: Gluten-sensitive idiopathic neuropathies

Other conditions

Antibodies to α-gliadin have been significantly increased in non-coeliacs individuals with oral ulceration.[36] Anti-α-gliadin antibodies are frequently found in coeliac disease(CD), to a lesser degree subclinical CD, but are also found in a subset who do not have the disease. The 1991 reference comes from a period when testing for subclinical CD was undeveloped. Of people with pseudo-exfoliation syndrome, 25% showed increased levels of anti-gliadin IgA.[37] One forth of people with Sjögren's syndrome had responses to gluten, of 5 that had positive response to gluten, only one could be confirmed as CD and another was potentially GSE, the remaining 3 appear to be gluten-sensitive. All were HLA-DQ2 and/or DQ8-positive.[38] Treatment to produce remission of Crohns disease(CrD) symptoms on elimination diet indicated the most important foods provoking symptoms were wheat and dairy.[39] A later paper showed little IgE mediated response except to the dairy,[40] while another paper showed no significant anti-food IgE association.[41] Crohn's disease (CrD) may have a link to wheat that is independent of gluten. CrD appears to be associated with high anti-yeast antibodies (ASCA - yeast antigens that are found in bread and other cereal derived products) and affected individuals lack lectin binding proteins such that the mannins in yeast, the antibodies that bind them and aggravate inflammatory colitis. One concern of the above studies is the high prevalence of markers for gluten-sensitive enteropathy, one has to question how idiopathic these conditions are if close examination for GSE has not been undertaken.

Gluten-allergy related sensitivities

Main article: Wheat allergy

Why treat gluten allergies as sensitivities? Over the last 10 years it has become apparent that allergies to certain substances do not behave in predictable ways. One clear example of this is exercise induced anaphylaxis and asthma, WDEIA (Wheat Dependent Exercise Induced Anaphylaxis) is now believed to be induced by ingested gluten that finds a way into the blood stream. This pathway is now believed responsible for some forms of eczema. Recent studies on two wheat allergens show that they possess the capability of bypassing the gut/blood barrier. The most active of these is ω-5 gliadin, a gluten component that is a strong allergen and causes WDEIA. Allergy tests may not reveal allergies to gluten because the unfractionated allergens are 'hidden' from these tests, and most currently available tests cannot detect these new allergens. Finally, allergies typically involve IgE, but some studies indicate there are several classes of responses, for example IgG1,IgG2, IgG4 that are associated with IgE.[42] Gluten allergy may be a cause of some idiopathic gluten sensitivity and gluten allergy can be a secondary consequence of gluten-sensitive enteropathy.

Comparative pathophysiology

Comparison of different forms of gluten sensitivity
Gluten-sensitive enteropathy Wheat allergy Gluten-sensitive idiopathic neuropathy
Typical symptoms steatorrhoea, malnutrition, diarrhea, lactose intolerance, food allergies eczema, asthma ataxia, peripheral neuropathies
Primary tissue targets epithelia of small intestine (epi) dermis, bronchi, intestines CNS, Peripheral nerves
Atypical pathologies other autoimmune diseases, chronic constipation, neuropathies, cancer (lymphoid) arthritis, migraines, anaphylaxis (exercise or aspirin induced) unknown
Secondary targets (common) blood (chemistry), bowel, nervous system, autoantigens connective tissue, CNS, vascular
Immunoglobin isotype IgA, IgG IgE, IgG, IgA IgG, IgA
Antibody recognition α/β,γ-gliadin (AGA), transglutaminase (ATA) albumins, globulins, prolamins (ω-gliadin)(AGA), glutelins (LMW)(AGA) α/β-gliadin
HLA associations DQ2.5, DQ8, DQ2.2/DQ7.5 unknown DQ2, DQ8?, DQ1?
Cellular immunity T-cells, Eosinophils, Monocytes Mast cells, Eosinophils unknown
Innate responses (α-gliadin) immune, increased permeability (ω-5 gliadin)- increased permeability unknown
Background & references Coeliac disease, GSEA conditions Wheat allergy IGS Neuropathies

Notes on table. Features of idiopathic neuropathy assume that all GSE cohort has been removed, assuming there is a gluten-sensitive, but not GSE contingent. Anti-gliadin antibodies covers all immunoglobulin isotypes and all gliadin isoforms. T-cell, Killer cell, and other gluten recognitions are covered in Gluten immunochemistry.

Gluten sources

Politics of Gluten-Free and Oats
Current guidelines
As a consequence, the current international standard for the "Gluten-free" designation, drafted in 1981 and agreed on in 1983[43] within the Codex Alimentarius (CA), states:

For the purpose of this standard, gluten is defined as those proteins, commonly found in wheat, triticale, rye, barley or oats to which some persons are intolerant.[44]

The American Dietetic Association’s Nutrition Care Manual position on the use of oats in a medically necessitated gluten-free diet is:

However, commercially available oats in the United States may be contaminated with small amounts of wheat, barley, or rye. For this reason, if you are newly diagnosed with celiac disease, you should not eat oats. Once your intestine heals, you may want to discuss the use of oats with your dietitian and physician.[45]

indicating the need for a separate standard of purity for people with gluten sensitivity.
New standards in development
Codex Alimentarius is undergoing revision and a revised standard will be presented at the meeting of the Codex Alimentarius Commission at the end of June 2008.[46] The proposed standard limits the amount of contaminant in product that would qualify that product as gluten-free:

Gluten-free foods are dietary foods a) consisting of or made only from one or more ingredients which do not contain wheat (i.e., all Triticum species, such as durum wheat, spelt, and kamut), rye, barley, oats1 or their crossbred varieties, and the gluten level does not exceed 20 mg/kg in total, based on the food as sold or distributed to the consumer, and/or b) consisting of one or more ingredients from wheat (i.e., all Triticum species, such as durum wheat, spelt, and kamut), rye, barley, oats1 or their crossbred varieties, which have been specially processed to remove gluten, and the gluten level does not exceed 20 mg/kg in total, based on the food as sold or distributed to the consumer.[47]

1 The Committee agreed to specify that the allowance of oats that are not contaminated with wheat, rye or barley in foods covered by the standard may be determined at national level."[47]

In realizing the benefit of whole oats in a gluten free diet, the Canadian Celiac Association sought to assure oats and oat products fulfill the gluten-free standards set by the Canadian Food Inspection Agency and Health Canada:

in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats.[48]

From the perspective of gluten sensitivity there is no single definition of gluten that concisely defines all potentially pathogenic glutens. With wheat allergies, there can be a wide spectrum of species that may trigger allergies with similar proteins, the omega-gliadin proteins have similar proteins found in oats at high frequency, but omega-gliadin allergy is not a predictor of oat allergy or intolerance.[49] A person can have an allergy to wheat, but not rye.[50]

Glutelins have not been characterized over broad taxa. With idiopathic gluten sensitivity, the antibodies that correlate with disease are anti-gliadin antibodies. Whether these antibodies are pathogenic or are simply indicators of circulating gliadin is unknown. For gluten-sensitive enteropathy, gliadin and homologous proteins from rye and barley cause disease. T-cell epitopes implicated in disease have been found in glutinous protein genes in all species sequenced within the tribe Triticeae.[51] Also, since barley is distantly related to wheat, but carries pathogenic epitopes it can be assumed that all members of Triticeae should carry T-cell sites capable of sustaining disease (see also Genetics of Triticeae). While often not explicitly stated in some standards, pathogenic glutens found in wheat are also found in Spelt and Kamut(both types of wheat), Triticale (a trans-species Triticeae hybrid).

The oat controversy

Oats are a species within the grass tribe Aveneae, which is in the Pooideae subfamily along with Triticeae (contains wheat, rye, barley and many other genera). Oats are the most closely related cereal species to Triticeae cereals. Some, but not all, cultivars of oat contain the pathogenic proteins that provoke a response in gluten sensitive individuals and those with celiac disease.[52] Alternatively, oat seeds appear similar to seeds of wheat, barley and rye; cross-contamination between these grains is difficult to resolve.

Further information: Oat-sensitive celiac disease

Origin of controversy

After World War II, wheat was suspected as the cause of coeliac disease, and the gluten from wheat was identified as a cause soon after. At the time, duodenal biopsy—the current "gold standard" of diagnosis—had not yet been developed;[53] indirect measures of disease were used. In two studies, three children were fed 75 to 150 grams of oats per day and developed symptoms. In three concurrent studies, 10 children and two adults were allowed to eat 28 to 60 grams of oats and developed no symptoms.[54] Since wheat, barley and sometimes rye are common contaminants in oats,[45][55] until this was investigated, oats were considered to be toxic to coeliacs.

Further information: History of coeliac disease

Current findings

While the problem of contamination has been known for several years, scientists' understanding of how oats and gluten are related continues to evolve. A study published in February 2011 uncovered differing levels of toxicity amongst different varieties of oat, indicating that cross-contamination is not the only reason why some oats provoke reactions in some people with a gluten intolerance.[52] A study published in June 2008 found that of 109 sources of oats screened, 85 had unacceptable levels of gluten from wheat, barley or rye.[56] Triticeae contaminated oats in the study came from many countries indicating that most sources of oats are unacceptable for GS based on contamination.

Tolerable levels of gluten

In summary of recent developments, oats can be tolerated in a gluten-free diet, but oat products should be limited in contamination from Triticeae derived gluten to 20 PPM (20 mg per kg). US states are free to deny the GF-label standard for oat products, if warranted (see Politics of Gluten-Free and oats).[57]

Gluten-free testing

As of February 2011, G12, the newest monoclonal antibody (moAb) available, is the only one proven to detect both cross-contamination in oats and also the inherent gluten / avenin that is only found in some varieties of oat.[52] Alternative methods of detection, while currently accepted by many gluten-free certification organizations, are not in fact able to detect this second form of gluten in oats. This may partially explain why some celiacs react to oats and others do not.

A barley-sensitive ELISA called the R5 sandwich assay does not detect gluten in any of 25 pure oat varieties, but it does detect barley, wheat and rye.[56] Disease-sensitive farming practices, antibody testing and species specific genetic testing are capable of producing pure oats.[56] In the United States, 3 domestic GF-brands are available and one brand imported from Ireland 'reckons' to be 99.95% pure oats.[58][59] Two brands in the United States use the R5 antibody test and claim to be below 20 PPM in defined gluten.[58][60] However, the R5 antibody test has not been proven to be as sensitive as the G12 test.

Further information: Antibody testing for gluten-free foods

Diets

Main article: Gluten-free diet

Gluten-free oats in a gluten-free diet. Gluten-free oats can provide a valuable source of fiber, vitamin B, iron, zinc and complex carbohydrates.[61] Recent studies show that gluten-sensitive individuals on a gluten-free diet often get too much simple starch, too little fibre and vitamin B. Currently most guidelines do not include oats in a gluten-free diet. While this is likely to change, oats are not recommended within a year of diagnosis because of the oat-sensitive enteropathy (ASE) risk, the desire to establish a clinical baseline and complexity of the contamination issue. Consuming oats when anti-gliadin antibodies or gliadin are present increases anti-avenin antibodies, and may promote ASE. Duodenal biopsy may be recommended after oat consumption is initiated. The DQ phenotype of all 3 ASE individuals studied so far indicated DQ2 homozygotes are at risk for ASE. Preferably, newly diagnosed celiacs seek the help of a dietician. However, guidelines are also available for the introduction of pure, uncontaminated oats into the gluten-free diet.[62]

Further information: Oat sensitivity

See also

References

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Gluten sensitivity
Conditions
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nervous system
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integumentary system
Antibodies
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cell/phys/auag/auab/comp, igrc

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