Gluten is a structural protein naturally found in certain cereal grains. [1] 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. [2] 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. [3] [4] Gluten makes up 75–85% of the total protein in bread wheat. [5]
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. [5] [6] [7] These properties, and its relatively low cost, make gluten valuable to both food and non-food industries. [7]
Wheat gluten is composed of mainly two types of proteins: the glutenins [8] and the gliadins, [9] 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. [10] These protein classes are collectively referred to as "gluten". [4] 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. [3]
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. [11] [12] [13] [14] These disorders are treated by a gluten-free diet. [14]
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. [5] [15] 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. [16] [17]
The formation of gluten affects the texture of the baked goods. [5] 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. [18] [19] 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. [20]
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 times. An increased moisture content in the dough enhances gluten development, [20] 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. [5] [21] [22]
In industrial production, a slurry of wheat flour is kneaded vigorously by machinery until the gluten agglomerates into a mass. [23] [ 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.[ 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. [23]
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. [24] 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. [25] Generally, higher gluten levels are associated with higher overall protein content. [26]
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. [27] [28] 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. [5]
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. [29]
Gluten is also used in cosmetics, hair products and other dermatological preparations. [30]
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. [31]
"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, [32] gluten ataxia and dermatitis herpetiformis (DH). [13]
The gluten peptides are responsible for triggering gluten-related disorders. [33] 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. [34] [35] To study mechanisms of this damage, laboratory experiments are done in vitro and in vivo. [36] [35] Among the gluten peptides, gliadin has been studied extensively. [33]
In the context of celiac disease, gliadin peptides are classified in basic and clinical research as immunogenic, depending on their mechanism of action: [33] [37]
At least 50 epitopes of gluten may produce cytotoxic, immunomodulatory, and gut-permeating activities. [39]
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. [41] [42] [43] In addition, oat products may be cross-contaminated with the other gluten-containing cereals. [42]
As of 2017 [update] , gluten-related disorders were increasing in frequency in different geographic areas. [40] [44] [45] [46] Some suggested explanations for this increase include the following: the growing westernization of diets, [44] the increasing use of wheat-based foods included in the Mediterranean diet, [47] [48] the progressive replacement of rice by wheat in many countries in Asia, the Middle East, and North Africa, [44] the higher content of gluten in bread and bakery products due to the reduction of dough fermentation time, [49] [50] and the development in recent years of new types of wheat with a higher amount of cytotoxic gluten peptides, [49] [51] 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." [52]
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. [53] 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. [4] [54] 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. [54] [55] [45] Added difficulties for diagnosis are the fact that serological markers (anti-tissue transglutaminase [TG2]) are not always present [56] and many people may have minor mucosal lesions, without atrophy of the intestinal villi. [57]
CD affects approximately 1–2% of the general population, [11] but most cases remain unrecognized, undiagnosed and untreated, and at risk for serious long-term health complications. [11] [45] [58] [59] People may suffer severe disease symptoms and be subjected to extensive investigations for many years, before a proper diagnosis is achieved. [55] Untreated CD may cause malabsorption, reduced quality of life, iron deficiency, osteoporosis, an increased risk of intestinal lymphomas, and greater mortality. [60] CD is associated with some other autoimmune diseases, such as diabetes mellitus type 1, thyroiditis, [61] gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and more. [53] [61]
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. [53] [55] [58]
CD with "non-classic symptoms" is the most common clinical type [55] and occurs in older children (over two years old), [55] adolescents, and adults. [55] 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 [58] both in children (at least in 43% of the cases [62] ) and adults. [58]
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. [63]
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. [64] [65] Recognized since 2010, [66] [67] it is included among gluten-related disorders. [66] 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. [67] [38]
NCGS is the most common syndrome of gluten intolerance, [66] [68] with a prevalence estimated to be 6-10%. [12] 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. [69] 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. [70] 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. [70] [71] 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. [70] [71]
People with NCGS may develop gastrointestinal symptoms, which resemble those of irritable bowel syndrome or wheat allergy, [66] [38] or a wide variety of non-gastrointestinal symptoms, such as headache, chronic fatigue, fibromyalgia, atopic diseases, allergies, neurological diseases, or psychiatric disorders, among others. [60] [67] [72] The results of a 2017 study suggest that NCGS may be a chronic disorder, as is the case with celiac disease. [73]
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. [67] 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. [74] [73] [67] ATIs may cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans. [75] [76]
People can also experience adverse effects of wheat as result of a wheat allergy. [32] 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. [77] Wheat allergy and celiac disease are different disorders. [32] [59] [78] 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. [56]
Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten. [79] 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. [80]
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. [80] [81]
Gluten ataxia accounts for 40% of ataxias of unknown origin and 15% of all ataxias. [80] [82] Less than 10% of people with gluten ataxia present any gastrointestinal symptom, yet about 40% have intestinal damage. [80]
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. [14] 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). [14] [83]
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. [14]
People with gluten-related disorders have to remove gluten from their diet strictly, so they need clear labeling rules. [84] The term "gluten-free" is generally used to indicate a supposed harmless level of gluten rather than a complete absence. [85] 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. [85] Regulation of the label "gluten-free" varies. [84]
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. [86]
By law in Brazil, all food products must display labels clearly indicating whether or not they contain gluten. [87]
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. [88]
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. [89] "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. [89] 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. [90]
All foods containing gluten as an ingredient must be labelled accordingly as gluten is defined as one of the 14 recognised EU allergens. [91]
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. [92]
Bread is a staple food prepared from a dough of flour and water, usually by baking. Throughout recorded history and around the world, it has been an important part of many cultures' diet. It is one of the oldest human-made foods, having been of significance since the dawn of agriculture, and plays an essential role in both religious rituals and secular culture.
Coeliac disease or celiac disease is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barley. Classic symptoms include gastrointestinal problems such as chronic diarrhoea, abdominal distention, malabsorption, loss of appetite, and among children failure to grow normally.
A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of prolamin proteins found in wheat, as well as barley, rye, and oats. The inclusion of oats in a gluten-free diet remains controversial, and may depend on the oat cultivar and the frequent cross-contamination with other gluten-containing cereals.
Gluten exorphins are a group of opioid peptides formed during the digestion of the gluten protein. These peptides work as external regulators for gastrointestinal movement and hormonal release. The breakdown of gliadin, a polymer of wheat proteins, creates amino acids that stop the gluten epitopes from entering the immune system to activate inflammatory reactions. During this process, gluten does not fully break down, thus increasing the presence of gluten exorphins. Because of this, researchers think this is what might lead to various diseases.
Gliadin is a class of proteins present in wheat and several other cereals within the grass genus Triticum. Gliadins, which are a component of gluten, are essential for giving bread the ability to rise properly during baking. Gliadins and glutenins are the two main components of the gluten fraction of the wheat seed. This gluten is found in products such as wheat flour. Gluten is split about evenly between the gliadins and glutenins, although there are variations found in different sources.
A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, germ, and bran, in contrast to refined grains, which retain only the endosperm.
Intestinal permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows nutrients to pass through the gut, while also maintaining a barrier function to keep potentially harmful substances from leaving the intestine and migrating to the body more widely. In a healthy human intestine, small particles can migrate through tight junction claudin pore pathways, and particles up to 10–15 Å can transit through the paracellular space uptake route. There is some evidence abnormally increased intestinal permeability may play a role in some chronic diseases and inflammatory conditions. The most well understood condition with observed increased intestinal permeability is celiac disease.
The specific carbohydrate diet (SCD) is a restrictive diet originally created to manage celiac disease; it limits the use of complex carbohydrates. Monosaccharides are allowed, and various foods including fish, aged cheese and honey are included. Prohibited foods include cereal grains, potatoes and lactose-containing dairy products. It is a gluten-free diet since no grains are permitted.
Wheat allergy is an allergy to wheat that typically presents itself as a food allergy, but can also be a contact allergy resulting from occupational exposure. Wheat allergy may be immunoglobulin E mediated or not and may involve mast cell response. Wheat allergy is rare. Prevalence in adults was estimated to be 0.21% in a 2012 study in Japan.
Triticeae is a botanical tribe within the subfamily Pooideae of grasses that includes genera with many domesticated species. Major crop genera found in this tribe include wheat, barley, and rye; crops in other genera include some for human consumption, and others used for animal feed or rangeland protection. Among the world's cultivated species, this tribe has some of the most complex genetic histories. An example is bread wheat, which contains the genomes of three species with only one being a wheat Triticum species. Seed storage proteins in the Triticeae are implicated in various food allergies and intolerances.
Gluten is the seed storage protein in mature wheat seeds. It is the sticky substance in bread wheat which allows dough to rise and retain its shape during baking. The same, or very similar, proteins are also found in related grasses within the tribe Triticeae. Seed glutens of some non-Triticeae plants have similar properties, but none can perform on a par with those of the Triticeae taxa, particularly the Triticum species. What distinguishes bread wheat from these other grass seeds is the quantity of these proteins and the level of subcomponents, with bread wheat having the highest protein content and a complex mixture of proteins derived from three grass species.
Gluten-related disorders is the term for the diseases triggered by gluten, including celiac disease (CD), non-celiac gluten sensitivity (NCGS), gluten ataxia, dermatitis herpetiformis (DH) and wheat allergy. The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.
Gluten-sensitive enteropathy–associated conditions are comorbidities or complications of gluten-related gastrointestinal distress. GSE has key symptoms typically restricted to the bowel and associated tissues; however, there are a wide variety of associated conditions. These include bowel disorders, eosinophilic gastroenteritis and increase with coeliac disease (CD) severity. With some early onset and a large percentage of late onset disease, other disorders appear prior to the coeliac diagnosis or allergic-like responses markedly increased in GSE. Many of these disorders persist on a strict gluten-free diet, and are thus independent of coeliac disease after triggering. For example, autoimmune thyroiditis is a common finding with GSE.
Anti-gliadin antibodies are produced in response to gliadin, a prolamin found in wheat. In bread wheat it is encoded by three different alleles, AA, BB, and DD. These alleles can produce slightly different gliadins, which can cause the body to produce different antibodies. Some of these antibodies can detect proteins in specific grass taxa such as Triticeae, while others react sporadically with certain species in those taxa, or over many taxonomically defined grass tribes.
Oat sensitivity represents a sensitivity to the proteins found in oats, Avena sativa. Sensitivity to oats can manifest as a result of allergy to oat seed storage proteins either inhaled or ingested. A more complex condition affects individuals who have gluten-sensitive enteropathy in which there is an autoimmune response to avenin, the glutinous protein in oats similar to the gluten within wheat. Sensitivity to oat foods can also result from their frequent contamination by wheat, barley, or rye particles.
The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses, class II mediated presentation, 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 gluten sensitive enteropathy, there are four types of recognition, innate immunity, HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.
Dermatitis herpetiformis (DH) is a chronic autoimmune blistering skin condition, characterised by intensely itchy blisters filled with a watery fluid. DH is a cutaneous manifestation of coeliac disease, although the exact causal mechanism is not known. DH is neither related to nor caused by herpes virus; the name means that it is a skin inflammation having an appearance similar to herpes.
FODMAPs or fermentable oligosaccharides, disaccharides, monosaccharides, and polyols are short-chain carbohydrates that are poorly absorbed in the small intestine and ferment in the colon. They include short-chain oligosaccharide polymers of fructose (fructans) and galactooligosaccharides, disaccharides (lactose), monosaccharides (fructose), and sugar alcohols (polyols), such as sorbitol, mannitol, xylitol, and maltitol. Most FODMAPs are naturally present in food and the human diet, but the polyols may be added artificially in commercially prepared foods and beverages.
Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is a controversial disorder which can cause both gastrointestinal and other problems.
The gluten challenge test is a medical test in which gluten-containing foods are consumed and (re-)occurrence of symptoms is observed afterwards to determine whether and how much a person reacts to these foods. The test may be performed in people with suspected gluten-related disorders in very specific occasions and under medical supervision, for example in people who had started a gluten-free diet without performing duodenal biopsy.
Similar proteins to the gliadin found in wheat exist as secalin in rye, hordein in barley, and avenins in oats, and are collectively referred to as 'gluten'. The gluten found in all of these grains has been identified as the component capable of triggering the immune-mediated disorder, celiac disease.
the distinctive feature that makes wheat unique is, precisely, the visco-elasticity of gluten. When the grain is milled and mixed with water, storage proteins form a dough, capable of retaining gas bubbles. These properties make wheat suitable for the preparation of a great diversity of food products
Given the unique properties of wheat gluten, it is not surprising that it has been the subject of intense attention by the food industry. (...) Gluten does have economic benefits over and above the more expensive milk- or soy-protein products (Table 1), and its functional properties, which other products cannot duplicate, give it a unique place among the various protein products. (...) Unlike whey and soy proteins, gluten or wheat proteins are not high in biological value and have not been widely researched for nutritional advantages.
There are at least 50 toxic epitopes in gluten peptides exerting cytotoxic, immunomodulatory, and gut-permeating activities.
Previous studies have shown that gliadin can cause an immediate and transient increase in gut permeability. This permeating effect is secondary to the binding of specific undigestible gliadin fragments to the CXCR3 chemokine receptor with subsequent release of zonulin, a modulator of intercellular tight junctions. This process takes place in all individuals who ingest gluten. For the majority, these events do not lead to abnormal consequences. However, these same events can lead to an inflammatory process in genetically predisposed individuals when the immunologic surveillance system mistakenly recognizes gluten as a pathogen.
It is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.
The increase in world-wide consumption of a Mediterranean diet, which includes a wide range of wheat-based foods, has possibly contributed to an alarming rise in the incidence of wheat (gluten?)-related disorders.1, 2
mechanization of farming and the growing industrial use of pesticides have favored the development of new types of wheat with a higher amount of toxic gluten peptides that cause the development of gluten-related disorders
Furthermore, a role for the FODMAP (eg, fructans) component of wheat as the sole trigger for symptoms is somewhat doubtful, because many patients with NCWS report resolution of symptoms after the withdrawal of wheat and related cereals, while continuing to ingest vegetables and fruits with high FODMAP content in their diets.59 On the whole, it is conceivable that more than one culprit may be involved in symptoms of NCWS (as they are currently defined), including gluten, other wheat proteins, and FODMAPs.60–62
Although intolerance to fructans and other FODMAPs may contribute to NCGS, they may only explain gastrointestinal symptoms and not the extraintestinal symptoms observed in NCGS patients, such as neurologic dysfunction, psychological disturbances, fibromyalgia, and skin rash.15 Therefore, it is unlikely that they are the sole cause of NCGS.