Summary of Gluten
Primary Information, Benefits, Effects, and Important Facts
This page on Gluten is currently marked as in-progress. We are still compiling research.
A lot of the research on gluten is done in the context of celiac disease (CD), a genetic autoimmune disease characterized by intestinal damage and an increased immune response as a result of gliadin consumption, a component of gluten. People with CD should avoid gluten to avoid this damage. Untreated CD combined with continued gluten intake is associated with a greater risk of death. People without CD or people with CD that also avoid gluten do not experience this increased risk.
Non-Celiac Gluten Sensitivity (NCGS) is another big topic for gluten researchers. There is some evidence to suggest people with non-celiac intestinal disorders like Irritable Bowel Syndrome (IBS) are more likely to experience flatulence, pain, and nausea after consuming gluten than people with healthy intestinal tracts. However, people with NCGS do not experience the same level of damage after eating gluten than people with CD. So, the discomfort of people with NCGS may be better explained by other carbohydrates associated with gluten, rather than autoimmune damage. Researchers examining self-diagnosis of gluten sensitivity suggest that many people with NCGS do not actually display any sensitivity and the symptoms may be the result of discussions related to gluten causing intestinal problems, also known as a 'nocebo' effect.
People with CD should avoid gluten at all costs, while people with other intestinal disorders may experience mild to severe discomfort after gluten consumption, possibly due to wheat's ability to produce gas. There is currently no evidence that gluten causes tissue damage when consumed by people without CD.
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1.1. Sources and Structure
Gluten refers to a group of proteins found in numerous grain products that form large interconnected structures called gluten-protein complexes during the cooking process. These complexes are responsible for bread rising while also providing structure and elasticity to the finished product. Usually, gluten is not a single molecule. Rather, 75% of it is made up of proteins like prolamins (on a dry weight basis) with additional carbohydrates and lipids. In the case of wheat glutens, the proteins are glutenins and gliadins. The latter are responsible for many of the intestinal concerns surrounding gluten due to their interactions with the immune system. Wheat gluten is made up of at least 50 individual components.
Prolamins are found in other grains, including barley, rye, and corn. They are hordein, secalin, and zein respectively. Avenin, found in oats, is also a prolamin. In a few cases, these prolamins can also influence celiac disease as is the case with oat intolerance,  although gliadin is the major culprit.
Gluten refers to a mixture of proteins called prolamins and other compounds, which exist in grains as storage proteins. Their content and manipulation can influence the composition and taste of bread products, but the gliadin prolamins cause a reaction in people with celiac disease.
2Peripheral Organ Systems
Gluten has been researched in the context of non-celiac gluten sensitivity (NCGS), which is sometimes called non-celiac wheat sensitivity. NCGS is characterized by a sensitivity to gluten in people who do not have celiac disease. This effect was first observed in clinical practice, where patients showing symptoms of irritable bowel syndrome (IBS) sometimes responded well to gluten-free diets. NCGS is neither celiac disease nor an allergic reaction to wheat and tends to be self-diagnosed (quite poorly, one study noted that 85.96% of subjects who self-reported intolerance to gluten did not have any response to gluten after testing) with one study reporting an occurrance rate of 6.88% in a sample of 392 patients.
The first trial assessing NCGS found that, in a small group of people given gluten-containing or gluten-free muffins, reports of side-effects like tiredness and bloating were higher in the gluten group at 68% of subjects than in the control group (40%) with no apparent relation to HLA-DQ2 and/or HLA-DQ8. A follow-up study of much larger size, investigating patients with IBS-like symptoms on a standard elimination diet (no cow's milk, eggs, tomato, or chocolate) who were randomized into two groups, one that ate no wheat and one that ate an additional 30g of wheat, noted that patients consuming wheat experienced more intestinal symptoms than the group not consuming wheat, when compared to their baseline values. Other studies assessing patients showing IBS-like symptoms also noted that gluten seems to be comparatively worse than non-gluten controls or placebo.
A rechallenge study during which gluten was given before and after a dietary reduction in FODMAPs (short-chain carbohydrates known to promote intestinal distress by fermenting and producing gas) found that gluten didn't promote intestinal distress on a low FODMAP diet, suggesting that perhaps FODMAPs are a major cause of sensitivity. Wheat, rye, and barley are known to possess fructan FODMAPs.
People that report sensitivity to gluten despite not being diagnosed with celiac disease may exhibit intestinal symptoms of discomfort, but more research is needed to determine whether gluten or other carbohydrates like FODMAPs are the cause. There is a lack of evidence on people who claim gluten sensitivity but do not have any symptoms.
3Other Medical Conditions
3.1. Celiac Disease
Celiac disease (CD) is a genetic disease associated with gluten because when somebody with CD ingests gluten, their body undergoes an autoimmune response to varying degrees. This response can be relatively minor (studies have found people with CD who were previously unaware that they had it) or potentially life-threatening. The best way to avoid this intestinal damage is to avoid gluten. Initially, this effect was thought to be exclusive to Europeans, due to early problems with accurate diagnosis in developing countries. CD is estimated to affect 0.5-1% of humans. The risk of having CD rises to 20% if one or more parents have CD.
Diagnosis of celiac disease is still not 100% accurate, with biomarkers such as Human Leuckocyte Antigen (HLA) DQ2/8 and anti-endomysial/anti-tissue transglutaminase antibodies being important to the diagnosis. Biopsies also used. However, biopsies may not be fully satisfactory and a few celiacs are considered seronegative, meaning blood-based biomarkers seen in most CD sufferers are not present. Regardless, unmanaged CD is associated with a greater mortality rate.
Gluten is not a single problematic compound, but rather a group of related prolamins that can trigger an autoimmune response. The most common prolamin is gliadin, a component of gluten.
Celiac disease is a somewhat rare (approximately 1% rate of occurrence) genetic disorder of the intestines during which the body exhibits an autoimmune responses after gliadin consumption, and potentially other related prolamins.