Gluten
Gluten is a structural protein naturally found in certain cereal grains.<ref>Hervé This, « Who discovered the gluten and who discovered its production by lixiviation? », Notes Académiques de l'Académie d'Agriculture de France/Academic Notes from the French Academy of Agriculture, vol. 3, no 3, 2002, p. 1–11
Template:Cite journal</ref> The term gluten usually refers to the elastic network of a wheat grain's proteins, gliadin and glutenin primarily, that forms readily with the addition of water and often kneading in the case of bread dough.<ref name="t022">Template:Cite book</ref> The types of grains that contain gluten include all species of wheat (common wheat, durum, spelt, khorasan, emmer, and einkorn), and barley, rye, and some cultivars of oat; moreover, cross hybrids of any of these cereal grains also contain gluten, e.g. triticale.<ref name="FDAlabeling2007">Template:Cite web</ref><ref name=Biesiekierski2017>Template:Cite journal</ref> Gluten makes up 75–85% of the total protein in bread wheat.<ref name="shewry1" />
Glutens, especially Triticeae glutens, have unique viscoelastic and adhesive properties, which give dough its elasticity, helping it rise and keep its shape and often leaving the final product with a chewy texture.<ref name=shewry1/><ref name=LamacchiaCamarca2014>Template:Cite journal</ref><ref name=DayAugustin2006>Template:Cite journal</ref> These properties, and its relatively low cost, make gluten valuable to both food and non-food industries.<ref name=DayAugustin2006 />
Wheat gluten is composed of mainly two types of proteins: the glutenins<ref>Template:Cite book</ref> and the gliadins,<ref>Template:Cite journal</ref> which in turn can be divided into high molecular and low molecular glutenins and α/β, γ and Ω gliadins. Its homologous seed storage proteins, in barley, are referred to as hordeins, in rye, secalins, and in oats, avenins.<ref>Template:Cite book</ref> These protein classes are collectively referred to as "gluten".<ref name=Biesiekierski2017 /> The storage proteins in other grains, such as maize (zeins) and rice (rice protein), are sometimes called gluten, but they do not cause harmful effects in people with celiac disease.<ref name=FDAlabeling2007 />
Gluten can trigger adverse, inflammatory, immunological, and autoimmune reactions in some people. The spectrum of gluten related disorders includes celiac disease in 1–2% of the general population, non-celiac gluten sensitivity in 0.5–13% of the general population, as well as dermatitis herpetiformis, gluten ataxia and other neurological disorders.<ref name=LundinWijmenga2015 /><ref name=MolinaInfanteSantolaria /><ref name=LudvigssonLeffler2013 /><ref name=ZisHadjivassiliou2019 /> These disorders are treated by a gluten-free diet.<ref name=ZisHadjivassiliou2019 />
Uses
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Bread products
[edit]Gluten forms when glutenin molecules cross-link via disulfide bonds to form a submicroscopic network attached to gliadin, which contributes viscosity (thickness) and extensibility to the mix.<ref name="shewry1">Template:Cite journal</ref><ref>Template:Cite web</ref> If this dough is leavened with yeast, fermentation produces carbon dioxide bubbles, which, trapped by the gluten network, cause the dough to rise. Baking coagulates the gluten, which, along with starch, stabilizes the shape of the final product. Gluten content has been implicated as a factor in the staling of bread, possibly because it binds water through hydration.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
The formation of gluten affects the texture of the baked goods.<ref name=shewry1/> Gluten's attainable elasticity is proportional to its content of glutenins with low molecular weights, as this portion contains the preponderance of the sulfur atoms responsible for the cross-linking in the gluten network.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Using flour with higher gluten content leads to chewier doughs such as those found in pizza and bagels, while using flour with less gluten content yields tender baked goods such as pastry products.<ref name="Baking Technology, Bread">Template:Cite web</ref>
Generally, bread flours are high in gluten (hard wheat); pastry flours have a lower gluten content. Kneading promotes the formation of gluten strands and cross-links, creating baked products that are chewier (as opposed to more brittle or crumbly). The "chewiness" increases as the dough is kneaded for longer. An increased moisture content in the dough enhances gluten development,<ref name="Baking Technology, Bread"/> and very wet doughs left to rise for a long time require no kneading (see no-knead bread). Shortening inhibits formation of cross-links and is used, along with diminished water and less kneading, when a tender and flaky product, such as a pie crust, is desired.
The strength and elasticity of gluten in flour is measured in the baking industry using a farinograph. This gives the baker a measurement of quality for different varieties of flours when developing recipes for various baked goods.<ref name=shewry1/><ref>Template:Cite web</ref><ref>Template:Cite journal</ref>
Added gluten
[edit]In industrial production, a slurry of wheat flour is kneaded vigorously by machinery until the gluten agglomerates into a mass.<ref name="sakhare">Template:Cite journal</ref>Template:Failed verification This mass is collected by centrifugation, then transported through several stages integrated in a continuous process. About 65% of the water in the wet gluten is removed by means of a screw press; the remainder is sprayed through an atomizer nozzle into a drying chamber, where it remains at an elevated temperature for a short time to allow the water to evaporate without denaturing the gluten.Template:Citation needed The process yields a flour-like powder with a 7% moisture content, which is air cooled and pneumatically transported to a receiving vessel. In the final step, the processed gluten is sifted and milled to produce a uniform product.<ref name=sakhare/>
This flour-like powder, when added to ordinary flour dough, may help improve the dough's ability to increase in volume. The resulting mixture also increases the bread's structural stability and chewiness.<ref>Template:Cite book</ref> Gluten-added dough must be worked vigorously to induce it to rise to its full capacity; an automatic bread machine or food processor may be required for high-gluten kneading.<ref>Template:Cite book</ref> Generally, higher gluten levels are associated with higher overall protein content.<ref>Template:Cite magazine</ref>
Imitation meats
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Gluten, especially wheat gluten (seitan), is often the basis for imitation meats resembling beef, chicken, duck (see mock duck), fish and pork. When cooked in broth, gluten absorbs some of the surrounding liquid (including the flavor) and becomes firm to the bite.<ref>Template:Cite book</ref><ref>Template:Cite web</ref> This use of gluten is a popular means of adding supplemental protein to many vegetarian diets. In home or restaurant cooking, wheat gluten is prepared from flour by kneading the flour under water, agglomerating the gluten into an elastic network known as a dough, and then washing out the starch.<ref name=shewry1/>
Other consumer products
[edit]Gluten is often present in beer and soy sauce, and can be used as a stabilizing agent in more unexpected food products, such as ice cream and ketchup. Foods of this kind may therefore present problems for a small number of consumers because the hidden gluten constitutes a hazard for people with celiac disease and gluten sensitivities. The protein content of some pet foods may also be enhanced by adding gluten.<ref>Template:Cite web</ref>
Gluten is also used in cosmetics, hair products and other dermatological preparations.<ref>Template:Cite journal</ref>
Animal feed
[edit]Wheat gluten is used both as a protein source and binding ingredient in pet foods. Wheat gluten imported from China adulterated with melamine used in pet foods was considered to have caused harm in many countries in 2007.<ref>Template:Cite web</ref>
Disorders
[edit]"Gluten-related disorders" is the umbrella term for all diseases triggered by gluten, which include celiac disease (CD), non-celiac gluten sensitivity (NCGS), wheat allergy, <ref name=Costantino22>Template:Cite journal</ref> gluten ataxia and dermatitis herpetiformis (DH).<ref name=LudvigssonLeffler2013>Template:Cite journal</ref>
Pathophysiological research
[edit]The gluten peptides are responsible for triggering gluten-related disorders.<ref name=LammersHerrera2018 /> In people who have celiac disease, the peptides trigger an immune response that causes injury of the intestines, ranging from inflammation to partial or total destruction of the intestinal villi.<ref name=DicksonStreutker2006>Template:Cite journal</ref><ref name=StovenMurray2013 /> To study mechanisms of this damage, laboratory experiments are done in vitro and in vivo.<ref name=KupferJabri2012>Template:Cite journal</ref><ref name=StovenMurray2013>Template:Cite journal</ref> Among the gluten peptides, gliadin has been studied extensively.<ref name=LammersHerrera2018 />
In vitro and in vivo studies
[edit]In the context of celiac disease, gliadin peptides are classified in basic and clinical research as immunogenic, depending on their mechanism of action:<ref name=LammersHerrera2018>Template:Cite journal</ref><ref name=SilanoVincentini2009>Template:Cite journal</ref>
- The peptides are those capable of directly affecting cells and intestinal preparations in vitro, producing cellular damage in vivo and eliciting the innate immune response.<ref name=LammersHerrera2018 /><ref name=SilanoVincentini2009 /> In vitro, the peptides promote cell apoptosis (a form of programmed cell death) and inhibit the synthesis of nucleic acids (DNA and RNA) and proteins, reducing the viability of cells.<ref name=ElliRoncoroni2015 /> Experiments in vivo with normal mice showed that they cause an increase in cell death and the production of interferon type I (an inflammatory mediator).<ref name=LammersHerrera2018 /> In vitro, gluten alters cellular morphology and motility, cytoskeleton organization, oxidative balance, and tight junctions.<ref name=Fasano2011>Template:Cite journal</ref><ref name=ElliRoncoroni2015>Template:Cite journal</ref><ref name=LeonardSapone2017 />
- The immunogenic peptides are those able to activate T cells in vitro.<ref name=LammersHerrera2018 />
At least 50 epitopes of gluten may produce cytotoxic, immunomodulatory, and gut-permeating activities.<ref name=Fasano2011 />
The effect of oat peptides (avenins) in celiac people depends on the oat cultivar consumed because of prolamin genes, protein amino acid sequences, and the immunotoxicity of prolamins which vary among oat varieties.<ref name=PenaginiDilillo>Template:Cite journal</ref><ref name=DeSouzaDeschenes2016>Template:Cite journal</ref><ref name=CominoMoreno2015>Template:Cite journal</ref> In addition, oat products may be cross-contaminated with the other gluten-containing cereals.<ref name="DeSouzaDeschenes2016"/>
Incidence
[edit]Template:As of, gluten-related disorders were increasing in frequency in different geographic areas.<ref name=LeonardSapone2017>Template:Cite journal</ref><ref name=TovoliMasi>Template:Cite journal</ref><ref name=LionettiGatti2015>Template:Cite journal</ref><ref name=SaponeBai2012>Template:Cite journal Template:Open access</ref> Some suggested explanations for this increase include the following: the growing westernization of diets,<ref name=TovoliMasi /> the increasing use of wheat-based foods included in the Mediterranean diet,<ref name=VoltaCaioQuestionsQuotation>Template:Cite journal</ref><ref name=GuandaliniPolanco>Template:Cite journal</ref> the progressive replacement of rice by wheat in many countries in Asia, the Middle East, and North Africa,<ref name=TovoliMasi /> the higher content of gluten in bread and bakery products due to the reduction of dough fermentation time,<ref name="VoltaCaioQuestions">Template:Cite journal</ref><ref name="GobbettiGiuseppe2007">Template:Cite journal</ref> and the development in recent years of new types of wheat with a higher amount of cytotoxic gluten peptides,<ref name="VoltaCaioQuestions" /><ref name="Belderok">Template:Cite journal</ref> However, a 2020 study that grew and analyzed 60 wheat cultivars from between 1891 and 2010 found no changes in albumin/globulin and gluten contents over time. "Overall, the harvest year had a more significant effect on protein composition than the cultivar. At the protein level, we found no evidence to support an increased immunostimulatory potential of modern winter wheat."<ref name="Scherf">Template:Cite journal</ref>
Celiac disease
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Celiac disease (CD) is a chronic, multiple-organ autoimmune disorder primarily affecting the small intestine caused by the ingestion of wheat, barley, rye, oats, and derivatives, that appears in genetically predisposed people of all ages.<ref name=":0">Template:Cite journal</ref> CD is not only a gastrointestinal disease, because it may involve several organs and cause an extensive variety of non-gastrointestinal symptoms, and most importantly, it may be apparently asymptomatic.<ref name=Biesiekierski2017 /><ref name=WGO2016>Template:Cite web</ref> Many asymptomatic people become accustomed to living with a chronic bad health status as if it were normal, but they are able to recognize that they actually had symptoms related to celiac disease after starting a gluten-free diet and improvement occurs.<ref name=WGO2016 /><ref name=LudvigssonCard /><ref name=LionettiGatti2015 /> Added difficulties for diagnosis are the fact that serological markers (anti-tissue transglutaminase [TG2]) are not always present<ref name=NEJM2012>Template:Cite journal</ref> and many people may have minor mucosal lesions, without atrophy of the intestinal villi.<ref name=BoldRostami>Template:Cite journal</ref>
CD affects approximately 1–2% of the general population,<ref name=LundinWijmenga2015>Template:Cite journal</ref> but most cases remain unrecognized, undiagnosed and untreated, and at risk for serious long-term health complications.<ref name=LundinWijmenga2015 /><ref name=LionettiGatti2015 /><ref name=Fasano2005Pediatric>Template:Cite journal</ref><ref name=ElliBranchi>Template:Cite journal</ref> People may suffer severe disease symptoms and be subjected to extensive investigations for many years, before a proper diagnosis is achieved.<ref name=LudvigssonCard>Template:Cite journal</ref> Untreated CD may cause malabsorption, reduced quality of life, iron deficiency, osteoporosis, an increased risk of intestinal lymphomas, and greater mortality.<ref name=LebwoholLudvigsson>Template:Cite journal</ref> CD is associated with some other autoimmune diseases, such as diabetes mellitus type 1, thyroiditis,<ref name=LundinWijmenga>Template:Cite journal</ref> gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and more.<ref name=":0" /><ref name=LundinWijmenga />
CD with "classic symptoms", which include gastrointestinal manifestations such as chronic diarrhea and abdominal distention, malabsorption, loss of appetite, and impaired growth, is currently the least common presentation form of the disease and affects predominantly small children generally younger than two years of age.<ref name=":0" /><ref name=LudvigssonCard /><ref name=Fasano2005Pediatric />
CD with "non-classic symptoms" is the most common clinical type<ref name=LudvigssonCard /> and occurs in older children (over two years old),<ref name=LudvigssonCard /> adolescents, and adults.<ref name=LudvigssonCard /> 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<ref name=Fasano2005Pediatric /> both in children (at least in 43% of the cases<ref name=VriezingaSchweizer>Template:Cite journal</ref>) and adults.<ref name=Fasano2005Pediatric />
Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function.<ref>Template:Cite journal</ref>
Non-celiac gluten sensitivity
[edit]Non-celiac gluten sensitivity (NCGS) is described as a condition of multiple symptoms that improves when switching to a gluten-free diet, after celiac disease and wheat allergy are excluded.<ref name=NijeboerBontkes>Template:Cite journal</ref><ref>Template:Cite journal</ref> Recognized since 2010,<ref name=CatassiBai /><ref name=FasanoSapone2015>Template:Cite journal</ref> it is included among gluten-related disorders.<ref name=CatassiBai /> Its pathogenesis is not yet well understood, but the activation of the innate immune system, the direct negative effects of gluten and probably other wheat components, are implicated.<ref name=FasanoSapone2015 /><ref name=ElliRoncoroni2015/>
NCGS is the most common syndrome of gluten intolerance,<ref name=CatassiBai /><ref name=CzajaBulsa>Template:Cite journal</ref> with a prevalence estimated to be 6-10%.<ref name=MolinaInfanteSantolaria>Template:Cite journal</ref> NCGS is becoming a more common diagnosis, but its true prevalence is difficult to determine because many people self-diagnose and start a gluten-free diet, without having previously tested for celiac disease or having the dietary prescription from a physician.<ref name="Igbinedion2017">Template:Cite journal</ref> People with NCGS and gastrointestinal symptoms remain habitually in a "no man's land", without being recognized by the specialists and lacking the adequate medical care and treatment.<ref name=VerduArmstrong2009>Template:Cite journal</ref> Most of these people have a long history of health complaints and unsuccessful consultations with numerous physicians, trying to get a diagnosis of celiac disease, but they are only labeled as irritable bowel syndrome.<ref name=VerduArmstrong2009 /><ref name="mansueto-etal-2014" /> A consistent although undefined number of people eliminate gluten because they identify it as responsible for their symptoms and these improve with the gluten-free diet, so they self-diagnose as NCGS.<ref name=VerduArmstrong2009 /><ref name="mansueto-etal-2014">Template:Cite journal</ref>
People with NCGS may develop gastrointestinal symptoms, which resemble those of irritable bowel syndrome or wheat allergy,<ref name=CatassiBai>Template:Cite journal</ref><ref name=ElliRoncoroni2015 /> or a wide variety of non-gastrointestinal symptoms, such as headache, chronic fatigue, fibromyalgia, atopic diseases, allergies, neurological diseases, or psychiatric disorders, among others.<ref name=LebwoholLudvigsson /><ref name=FasanoSapone2015 /><ref name=VoltaCaio2015>Template:Cite journal</ref> The results of a 2017 study suggest that NCGS may be a chronic disorder, as is the case with celiac disease.<ref name=VoltaDeGiorgio2019 />
Besides gluten, additional components present in wheat, rye, barley, oats, and their derivatives, including other proteins called amylase-trypsin inhibitors (ATIs) and short-chain carbohydrates known as FODMAPs, may cause NCGS symptoms.<ref name=FasanoSapone2015 /> As of 2019, reviews conclude that although FODMAPs present in wheat and related grains may play a role in non-celiac gluten sensitivity, they only explain certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with non-celiac gluten sensitivity may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.<ref name=Verbeke2018>Template:Cite journal</ref><ref name=VoltaDeGiorgio2019>Template:Cite journal</ref><ref name="FasanoSapone2015" /> ATIs may cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans.<ref name="BaroneTroncone2014">Template:Cite journal</ref><ref name="junker-etal-2012">Template:Cite journal</ref>
Wheat allergy
[edit]People can also experience adverse effects of wheat as result of a wheat allergy. <ref name=Costantino22/> As with most allergies, a wheat allergy causes the immune system to respond abnormally to a component of wheat that it treats as a threatening foreign body. This immune response is often time-limited and does not cause lasting harm to body tissues.<ref>Template:Cite web</ref> Wheat allergy and celiac disease are different disorders. <ref name=Costantino22/><ref name=ElliBranchi/><ref>Template:Cite web</ref> Gastrointestinal symptoms of wheat allergy are similar to those of celiac disease and non-celiac gluten sensitivity, but there is a different interval between exposure to wheat and onset of symptoms. An allergic reaction to wheat has a fast onset (from minutes to hours) after the consumption of food containing wheat and could include anaphylaxis.<ref name=NEJM2012 />
Gluten ataxia
[edit]Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten.<ref name="sapone-etal-2010-b">Template:Cite journal</ref> With gluten ataxia, damage takes place in the cerebellum, the balance center of the brain that controls coordination and complex movements like walking, speaking and swallowing, with loss of Purkinje cells. People with gluten ataxia usually present gait abnormality or incoordination and tremor of the upper limbs. Gaze-evoked nystagmus and other ocular signs of cerebellar dysfunction are common. Myoclonus, palatal tremor, and opsoclonus-myoclonus may also appear.<ref name="HadjivassiliouSanders2015" />
Early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression. The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of neurons in the cerebellum as a result of gluten exposure is irreversible.<ref name="HadjivassiliouSanders2015" /><ref name="MitomaAdhikari2016">Template:Cite journal</ref>
Gluten ataxia accounts for 40% of ataxias of unknown origin and 15% of all ataxias.<ref name="HadjivassiliouSanders2015">Template:Cite journal</ref><ref name="pmid12566288">Template:Cite journal</ref> Less than 10% of people with gluten ataxia present any gastrointestinal symptom, yet about 40% have intestinal damage.<ref name="HadjivassiliouSanders2015" />
Other neurological disorders
[edit]In addition to gluten ataxia, gluten sensitivity can cause a wide spectrum of neurological disorders, which develop with or without the presence of digestive symptoms or intestinal damage.<ref name=ZisHadjivassiliou2019>Template:Cite journal</ref> These include peripheral neuropathy, epilepsy, headache, encephalopathy, vascular dementia, and various movement disorders (restless legs syndrome, chorea, parkinsonism, Tourette syndrome, palatal tremor, myoclonus, dystonia, opsoclonus myoclonus syndrome, paroxysms, dyskinesia, myorhythmia, myokymia).<ref name=ZisHadjivassiliou2019 /><ref name=VinagreAragonGrunewald2018>Template:Cite journal</ref>
The diagnosis of underlying gluten sensitivity is complicated and delayed when there are no digestive symptoms. People who do experience gastrointestinal problems are more likely to receive a correct diagnosis and treatment. A strict gluten-free diet is the first-line treatment, which should be started as soon as possible. It is effective in most of these disorders. When dementia has progressed to an advanced degree, the diet has no beneficial effect. Cortical myoclonus appears to be treatment-resistant on both gluten-free diet and immunosuppression.<ref name=ZisHadjivassiliou2019 />
Labeling
[edit]People with gluten-related disorders have to remove gluten from their diet strictly, so they need clear labeling rules.<ref name=Diaz-AmigoPopping2012>Template:Cite journal</ref> The term "gluten-free" is generally used to indicate a supposed harmless level of gluten rather than a complete absence.<ref name=Akobeng2008>Template:Cite journal</ref> 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 of gluten per day is unlikely to cause intestinal damage in people with celiac disease, although it noted that few reliable studies had been done.<ref name=Akobeng2008/> Regulation of the label "gluten-free" varies.<ref name=Diaz-AmigoPopping2012 />
International standards
[edit]The Codex Alimentarius international standards for food labeling has a standard relating to the labeling of products as "gluten-free". It only applies to foods that would normally contain gluten.<ref>Template:Cite web</ref>
Brazil
[edit]By law in Brazil, all food products must display labels clearly indicating whether or not they contain gluten.<ref>Template:Cite web</ref>
Canada
[edit]Labels for all food products sold in Canada must clearly identify the presence of gluten if it is present at a level greater than 20 parts per million.<ref>Template:Cite web</ref>
European Union and United Kingdom
[edit]In the European Union, all prepackaged foods and non-prepacked foods from a restaurant, take-out food wrapped just before sale, or unpackaged food served in institutions must be identified if gluten-free.<ref name="fsa2016">Template:Cite web</ref> "Gluten-free" is defined as 20 parts per million of gluten or less and "very low gluten" is 100 parts per million of gluten or less; only foods with cereal ingredients processed to remove gluten can claim "very low gluten" on labels.<ref name=fsa2016/> It is not allowed to label food as "gluten-free" when all similar food is naturally gluten-free, such as in the case of milk.<ref>Template:Cite book</ref>
All foods containing gluten as an ingredient must be labelled accordingly as gluten is defined as one of the 14 recognised EU allergens.<ref>Template:Cite web</ref>
United States
[edit]In the United States, gluten is not listed on labels unless added as a standalone ingredient. Wheat or other allergens are listed after the ingredient line. The US Food and Drug Administration (FDA) has historically classified gluten as "generally recognized as safe" (GRAS). In August 2013, the FDA issued a final ruling, effective August 2014, that defined the term "gluten-free" for voluntary use in the labeling of foods as meaning that the amount of gluten contained in the food is below 20 parts per million.<ref>Template:Cite web</ref>