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Summary of Gluten
Primary Information, Benefits, Effects, and Important Facts
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.
How to Take Gluten
Recommended dosage, active amounts, other details
Gluten is not a supplement and does not provide benefits to the body after ingestion. Supplementing gluten is not recommended. People with celiac disease should not consume gluten.
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Frequently Asked Questions about Gluten
Everything you need to know about the keto diet
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Scientific Research on Gluten
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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.
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.
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.
- Shwry PR, et al. Biotechnology of breadmaking: unraveling and manipulating the multi-protein gluten complex. Biotechnology (N Y). (1995)
- Anjum FM, et al. Wheat gluten: high molecular weight glutenin subunits--structure, genetics, and relation to dough elasticity. J Food Sci. (2007)
- Shewry PR, et al. The structure and properties of gluten: an elastic protein from wheat grain. Philos Trans R Soc Lond B Biol Sci. (2002)
- Arentz-Hansen H, et al. The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med. (2000)
- Gujral N, Freeman HJ, Thomson AB. Celiac disease: prevalence, diagnosis, pathogenesis and treatment. World J Gastroenterol. (2012)
- Hardy MY, et al. Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. J Autoimmun. (2015)
- Arentz-Hansen H, et al. The molecular basis for oat intolerance in patients with celiac disease. PLoS Med. (2004)
- Carroccio A, et al. Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity. Am J Gastroenterol. (2012)
- Biesiekierski JR, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial. Am J Gastroenterol. (2011)
- Capannolo A, et al. Non-Celiac Gluten Sensitivity among Patients Perceiving Gluten-Related Symptoms. Digestion. (2015)
- Shahbazkhani B, et al. Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial. Nutrients. (2015)
- Elli L, et al. Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge. Nutrients. (2016)
- Gibson PR, Shepherd SJ. Food choice as a key management strategy for functional gastrointestinal symptoms. Am J Gastroenterol. (2012)
- Biesiekierski JR, et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology. (2013)
- Van Belzen MJ, et al. A major non-HLA locus in celiac disease maps to chromosome 19. Gastroenterology. (2003)
- Rampertab SD, et al. Trends in the presentation of celiac disease. Am J Med. (2006)
- Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. (2001)
- Freeman HJ. Risk factors in familial forms of celiac disease. World J Gastroenterol. (2010)
- Samasca G, et al. Challenges in the celiac disease diagnosis; Prague consensus. Gastroenterol Hepatol Bed Bench. (2017)
- Bardella MT, et al. Serological markers for coeliac disease: is it time to change?. Dig Liver Dis. (2001)
- Taavela J, et al. A Prospective Study on the Usefulness of Duodenal Bulb Biopsies in Celiac Disease Diagnosis in Children: Urging Caution. Am J Gastroenterol. (2016)
- Volta U, et al. Seronegative celiac disease: Shedding light on an obscure clinical entity. Dig Liver Dis. (2016)
- Corrao G, et al. Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet. (2001)
- Sollid LM. Molecular basis of celiac disease. Annu Rev Immunol. (2000)
- James S, Montgomery P, Williams K. Omega-3 fatty acids supplementation for autism spectrum disorders (ASD). Cochrane Database Syst Rev. (2011)
- Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev Med Child Neurol. (2011)
- Mazahery H, et al. Vitamin D and Autism Spectrum Disorder: A Literature Review. Nutrients. (2016)
- Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev. (2005)
- Marí-Bauset S, et al. Evidence of the gluten-free and casein-free diet in autism spectrum disorders: a systematic review. J Child Neurol. (2014)
- Winburn E, et al. Parents' and child health professionals' attitudes towards dietary interventions for children with autism spectrum disorders. J Autism Dev Disord. (2014)
- Panksepp J. A neurochemical theory of autism. Trends in Neurosciences. (1979)
- Shattock P, Whiteley P. Biochemical aspects in autism spectrum disorders: updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets. (2002)
- van De Sande MM, van Buul VJ, Brouns FJ. Autism and nutrition: the role of the gut-brain axis. Nutr Res Rev. (2014)
- de Magistris L, et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. (2010)
- Dalton N, et al. Gut permeability in autism spectrum disorders. Autism Res. (2014)
- Dettmer K, et al. Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC-tandem mass spectrometry method to test the opioid excess theory. Anal Bioanal Chem. (2007)
- Cass H, et al. Absence of urinary opioid peptides in children with autism. Arch Dis Child. (2008)
- Millward C, et al. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database Syst Rev. (2008)
- Elder JH, et al. The gluten-free, casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord. (2006)
- Seung, et al. The gluten- and casein-free diet and autism: Communication outcomes from a preliminary double-blind clinical trial.. Journal of Medical Speech-Language Pathology. (2007)
- Navarro F, et al. Are 'leaky gut' and behavior associated with gluten and dairy containing diet in children with autism spectrum disorders?. Nutr Neurosci. (2015)
- Pusponegoro HD, et al. Gluten and casein supplementation does not increase symptoms in children with autism spectrum disorder. Acta Paediatr. (2015)
- Hyman SL, et al. The Gluten-Free/Casein-Free Diet: A Double-Blind Challenge Trial in Children with Autism. J Autism Dev Disord. (2016)
- Piwowarczyk A, et al. Gluten- and casein-free diet and autism spectrum disorders in children: a systematic review. Eur J Nutr. (2018)
- Sathe N, et al. Nutritional and Dietary Interventions for Autism Spectrum Disorder: A Systematic Review. Pediatrics. (2017)
- Buie T, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. (2010)
- Vasa RA, et al. Assessment and Treatment of Anxiety in Youth With Autism Spectrum Disorders. Pediatrics. (2016)
- Zwaigenbaum L, et al. Early Intervention for Children With Autism Spectrum Disorder Under 3 Years of Age: Recommendations for Practice and Research. Pediatrics. (2015)