(Published March 2013)

Think about what you ate for breakfast this morning. You might have had some fruit or protein, but you most likely ingested wheat. This is a probable assumption because wheat is the most widely consumed food group in the North American diet [1]. Common wheat-based breakfast foods such as pastries, bagels, granola bars, pancakes, cereal, muffins, and oats all contain flours or starches prepared with wheat, rye and barley grains [1]. When flours are mixed with water, the wheat proteins create a 3D network giving dough elastic and viscous properties that food-processing companies have chemically manipulated to formulate better quality foods [2]. Due to ease of industrial production of wheat flour and high availability, these companies have taken advantage of the main structural protein of wheat and utilized it as an ingredient for many other food items that do not have a dough base. Thus, even if you consciously did not eat wheat for breakfast you might have ingested wheat in other non-dough foods, such as dry roasted nuts, baked beans, processed meats and poultry, icings and frostings, chocolate, or seasonings and sauces1. So what is this highly valued wheat protein by the food industry and why should we care about it?

Gluten is the main structural protein in wheat and other grains. It is composed of two types of similar proteins called gliadins and glutenins [2]. Glutenins are simple proteins that can be easily broken down with secretions from the stomach, pancreas and small intestine. However, gliadins are bulkier and resistant to acidic secretions in the stomach. Enzymes further down in the digestive tract cannot chew them up, so they remain insoluble and stick to the small intestinal tube. Gliadins are formed from crossbreeding wheat plants and genetically modifying them for high production at harvest (i.e. altering wheat DNA to select genes that are resistant to harsh weather, fertilizer absorption and pesticide damage) [2]. With farmers creating these new hybrid wheat plants, they also created variant gluten proteins that some individuals’ bodies can have reactions to. For most of the population these proteins aren’t harmful and they eventually are scraped out of your body with mucus and other digested food, but for about 1% of the population these proteins are toxic [3]. For these people, gluten ingestion can present harmful effects in different organs with varying degrees of severity. For example, one individual may develop a painful skin rash and complain of intestinal discomfort, whereas another may suffer an anaphylactic attack and have troubles breathing after eating gluten. Due to the wide variability of symptoms wheat proteins can cause, gluten disorders are difficult to diagnose until the patient adjusts to a gluten-free diet and symptoms subside or disappear completely [2]. For this individual, they must abstain from ingesting food, beverages or medication that contain wheat, barley, rye and or oats for the rest of their life [1].

With high global consumption of gluten-laced food products more individuals are identifying illnesses that were originally diagnosed by a neurologist, psychologist, dermatologist or nutritionist to be symptoms caused by an underlying gluten disorder. Gastroenterologists are urging more patients to switch to a stringent gluten-free diet, and with this lifestyle change more health complications of gliadin toxicity are being uncovered. From statistics generated by clinician reports and confirmation obtained with the aid of laboratory research, there are 3 main forms of gluten-related disorders. This spectrum of gluten reactions entails celiac disease, wheat allergy and gluten sensitivity, and each evoke differential adverse reactions in the body’s immune system. In order to properly diagnose patients, clinicians need to be educated in what symptoms to recognize and how the existing forms of gluten-disorders are classified. Similarly, for clinicians to treat their patients and give adequate advice on managing the illness they must understand how gluten affects the body at a molecular biology level.

The most well-known and severe reaction to gluten exposure is celiac disease. It is a condition that results in damage to the lining of the small intestine and prevents nutrients from being absorbed into the blood stream. This damage is caused by accumulated gliadins that attach permanently to cells and disrupt their shape, which impairs their function of absorbing nutrients. The unhealthy intestinal cells eventually die and an inflammatory response is signaled from the gut to recruit a type of white blood cells, called lymphocytes, to destroy the gliadin protein and help stimulate growth of healthy intestinal cells. However, celiac disease is an autoimmune disease, which means the white blood cells are misdirected and attack healthy tissue that is mistakenly marked for destruction. These ‘search and destroy’ signals are specific to attack gliadin proteins and circulate in the blood to their final destination at the intestine, but sometimes they adhere to healthy tissues on the ride there. These signals, which take anywhere from weeks up to years to develop, can be concentrated at the intestinal tissue or migrate to other organs, such as the skin, joints, brain and heart [4]. This is problematic because these organs become infiltrated with lymphocytes when they aren’t supposed to and health complications result. Thus, not all celiac patients have the same symptoms (depending on where the signals migrate) and gluten affects each individual differently.

Classically, susceptible individuals suffer from gastrointestinal symptoms such as extreme abdominal pain, bloating, chronic diarrhea, weight loss, nausea, vomiting, and lactose intolerance [4]. Though from the immune system responding to inflammatory signals in organs away from the intestinal source, extra-intestinal symptoms can result from gluten exposure. These can include depression, fatigue, headaches, blistering skin rashes (called dermatitis herpetiformis), poor coordination (muscle spasms), seizures, joint pain, stunted growth and iron deficient anemia4. Due to damaged intestinal lining and malabsorption of vitamins, celiac individuals can become highly deficient in folic acid, vitamin B12, iron, calcium and vitamin D, which can attribute to the severity of the disease [5]. Celiac disease cannot be cured, but with compliance of a diet excluding gluten-containing food items recommended by a dietician, these symptoms can improve dramatically.

Celiac disease is most common in people of European origin and can be triggered by either environmental factors or genetics [6]. With genetic testing, doctors have found that individuals with the genes HLA-DQ2 and HLA-DQ8 are predisposed to develop an autoimmune reaction to gluten7. These genes produce DQ2 and DQ8, which are the ‘search and destroy’ signals that bind to gluten. However, presence of DQ2 and DQ3 isn’t the only factor for celiac disease and doctors are able to test patients’ blood for an increase in an antibody that recognizes an enzyme normally found in the intestinal cells, called transglutaminase [6]. Regardless of the detection method, celiac disease is becoming more prevalent and if its symptoms are not identified early in life then it can progress to severe gastrointestinal damage and, in rare cases, lymphoma (blood cancer) and infertility [6].

Another condition that stimulates an immune response in the body to gluten exposure, yet does not present with intestinal damage is classified as wheat allergy. It is less harmful than celiac disease because it involves your body responding to gluten as an allergic reaction, rather than an attack of healthy tissue by an autoimmune reaction. Allergic reactions are a buildup of a subpopulation of white blood cells to the skin or mucus area when a foreign allergen, or in this case gluten, comes in contact with it. These white blood cells are called basophils and they secrete chemical messengers called histamines, which signal your body to produce defense mechanisms such as mucus, tears, pain and inflammation. These ‘protection strategies’ are carried out because your body suspects that gluten is attacking it. Depending on the route of exposure to gluten, an allergic reaction to wheat can affect the skin, gastrointestinal tract or respiratory tract. Also, the intensity of the allergic reaction can vary with the type of gluten food product, for example eating cereal could produce a small rash, but eating toast results in hives.

The most common wheat allergies include baker’s asthma through inhalation, contact urticaria through skin contact and wheat-dependent, exercise-induced anaphylaxis through ingestion [6]. Baker’s asthma is usually developed in work environments that contain cereal flour and dusts that are inhaled and result in difficulty breathing, irritation and inflammation of the nose (rhinitis), chest tightness, coughing and wheezing [8]. Contact urticaria is an immediate skin rash with swelling, redness, itchiness or pain with direct contact of gluten food products to skin. These two allergies present with minimal health complications, however wheat-dependent, exercise-induced anaphylaxis can be deadly without diagnosis and EpiPen (emergency injectable epinephrine) administration upon attack. Individuals with this condition can experience an anaphylactic attack upon physical activity within hours after ingesting food without consciously being aware of a gluten ingredient. This attack includes symptoms of nausea, vomiting, respiratory distress, choking and hives [8].

Despite various routes of exposure and symptoms, wheat allergic reactions are all stimulated minutes to hours after gluten exposure and can be prevented through avoidance of gluten [6]. Its prevalence is found to be approximately 0.4% in the United States and about 0.5% in two population-based studies from the UK and one from Germany conducted over the last decade (2000-2010) [6]. Although wheat allergies are not strongly associated with certain genes, they are found to be heritable, which means other family members experience similar symptoms after gluten exposure. Family members can be diagnosed for gluten allergy by skin prick tests, where an area on the body is scratched and drops of purified wheat protein are tested, or by blood tests for antibodies that bind to the gliadin protein. Subsequently, these tests are followed by a dermatological or oral food challenge for symptom recurrence and final diagnosis of wheat allergy. Though having a wheat allergy is usually not life threatening, it is important to diagnose those individuals early in life who are afflicted by anaphylactic attacks upon ingestion of gluten.

On the other side of the gluten disorder spectrum is a condition that is gaining popularity through fad diets with scientific research proof to support its existence, called “nonceliac gluten sensitivity”. These individuals are gluten-reactive and experience adverse symptoms and distress within hours to days after gluten ingestion [6]. Symptoms can include intestinal irritation and abdominal pain, but they are mostly extraintestinal involving leg or arm numbness, depression, iron deficiency anemia, ‘foggy mind’, joint or muscle pain, headache, eczema, fatigue, and painful or itchy skin rashes [3]. Gluten sensitive patients report having similar, yet less severe, symptoms of celiac disease though the reaction is found by doctors to be neither autoimmune nor allergic. Diagnostic tests reveal that their small intestines are normal and healthy on endoscopic pictures (a long, flexible camera that looks at intestinal tissue) and they have no classical antibodies that recognize gluten proteins in their blood [6]. The diagnosis is usually made through elimination of other allergic and autoimmune mechanisms, since there are no detectable markers in the blood specific for gluten sensitivity. However, research has shown that gluten sensitivity elicits a slight immune reaction in the body with mild increase in white blood cells at the small intestinal lining and with gluten withdrawal the symptoms diminish or disappear [2]. From this information, doctors and patients should be wary that gluten can cause behavioural and psychological effects and that diagnosis of gluten sensitivity cannot be confirmed with classical immune markers for other well-studied gluten disorders.

Though the gluten-free diet has been shown to benefit individuals with gluten-related disorders, there is no evidence-based research to support that following a gluten-free diet in the general population is healthier or promotes weight loss [9]. In fact, more scientific research is available that demonstrates the positive health benefits of ingesting gluten and on the potential drawbacks in unnecessarily adopting a gluten-free diet. Not only do gluten-free baked goods contain higher fat content and total energy than their gluten-containing counterparts [10], but gluten-free items are deficient in whole grains and fiber, which have both been shown to be associated with improved body mass index (BMI) status [11]. In other words, a person is more likely better off eating a whole-grain wheat breakfast cereal than snacking on a bag of gluten-free pretzels, since the latter is actually helping you put on weight. Furthermore, in one study that monitored ten individuals (who had no medical need to avoid eating gluten) eating certified gluten-free foods in place of all grain products for one month, it was shown that their healthy, beneficial gut bacteria was significantly depleted [12]. This appeared to be due to wheat products having natural starches called fructans. These starches stimulate the growth of healthy bacteria in your gut and help your body stay healthy – a high composition of good bacteria in your colon is important to protect the gut from inflammatory diseases and cancer, and the body from heart disease.

This fad and lack of gluten in a healthy individual’s diets has received criticism from the scientific community, given that there are currently no statistics to support that gluten is the direct cause in weight gain and that it is unhealthy for the body. Indeed, the only justification the general public has for going gluten-free is that in doing so, they may reap the benefits of a general lifestyle change. In other words, the effect of reducing gluten items is most likely due to an improvement in people’s awareness in food choices and adopting a more well-balanced diet with more legumes, vegetables and protein in replacement of meals loaded with starches and including little to no vegetables. All in all, this speaks to the importance of proper diagnosis and education, so that gluten sensitive individuals can be properly treated, whilst the rest of the general public can be made aware of the facts pertaining to adopting a gluten-free diet.

With the U.S. market for gluten-free food products soaring to $4.2 billion in retail sales in 2012 and the increased number of patients describing symptoms related to gluten exposure, it is imperative that doctors and patients become knowledgeable of all conditions that exist under the gluten-disorder umbrella and how each illness affects the body’s immune system [13,6]. Since symptoms of gluten disorders can be misdiagnosed for other illnesses years before a gastroenterologist is referred, North Americans should become informed about the complications that can result with prolonged exposure to gluten and inquire if they have a family history of gluten-disorders. Conversely, people with gluten sensitivity that are planning to adjust or are already compliant with eating a gluten-free diet should contact a dietician to ensure their body is obtaining the nutritional quality it needs to stay healthy. Research towards furthering the understanding of gluten-disorders and how the human body’s immune system reacts to specific wheat proteins is ongoing. Scientists are developing medication that helps break down gliadin for celiac patients, characterizing the biochemical pathway in wheat-dependent, exercise-induced anaphylaxis, and determining an immune system profile to identify earlier diagnosis of gluten sensitivity. These scientific advances will help doctors increase awareness, provide effective treatment and ameliorate the quality of life of those affected by a gluten disorder.


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