GLU TEN - FREE
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ED PRODUC T S
Gluten Intolerance, Celiac Disease, and Wheat Allergy It is difficult for those who eat wheat with impunity to truly relate to, or understand, the lives of those who have celiac disease, gluten intolerance, or wheat allergy. Observing the shelf during a simple trip to the grocery store will demonstrate just how intertwined our lives are with wheat and other grains such as barley and rye. The histories of wheat and humans are indeed inseparable and have resulted in a food supply that could be described as inhospitable to those who cannot consume foods containing wheat, rye, or barley or ingredients derived from these common cereals. However, recent interest in gluten-free diets has resulted in increased options and variety for those who are celiac patients or have gluten intolerance, even though the primary market force for this proliferation has been those who can eat gluten but are selecting a gluten-free diet for other reasons. Product requirements for foods marketed to those with celiac disease do not differ from foods specifically marketed for gluten intolerance. Despite this, it is important to product developers to understand the differences between celiac disease, gluten intolerance, and wheat allergy because these differences give context to the requirements of the end consumer. Consumers adhering to a gluten-free diet will likely purchase foods meeting the criteria for people with celiac disease because food manufacturers generally do not produce noncertified gluten-free products. This chapter provides an overview of each condition. Additionally, to understand these conditions, it is of critical importance to understand what is meant by the
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term “gluten” and how it is used within the medical community, as that differs from how it is used by those in the field of food technology.
Gluten Common wheat flour is approximately 7–15% protein on a 14% moisture basis (1). Most proteins in wheat can be considered “storage proteins,” which are utilized by the germinating and growing seedling. Proteins that are considered “gluten” make up approximately 80% of the total storage proteins in the wheat kernel. Gluten comprises many different types of proteins, which are commonly classified using the Osborne classification system (2) This system allows for proteins with different properties to be separated and classified based on their solubilities. The common protein fractions in wheat include water-soluble proteins (albumins), proteins soluble in salt solution (globulins), proteins soluble in 70% aqueous ethanol (prolamins), and proteins soluble in dilute acids and bases (glutelins). Of these protein classes, the prolamins and glutelins are by far the largest components in wheat protein and make up 33 and 16%, respectively, of the total proteins in flour. These two classes of proteins, when combined, are known as “gluten” to those in the field of food technology. For food technologists, “gluten” is thought of as a functional combination of two specific types of protein, glutenin (a glutelin) and gliadin (a prolamin). Glutenin contributes elasticity and strength to wheat flour dough; when stretched, it resists “Gluten” means different things to and returns to its original shape. On the other different scientists: hand, gliadin stretches easily without resistance. • in food science, a combination of two proteins—glutenin and gliadin, Combined, these proteins provide a viscoelastic • in medical science, gliadin only. character to a dough, which allows for the entrapment of gas and prevents that gas from escaping. Bubbles in dough can expand and allow dough to become sufficiently porous to provide a desirably textured low-density product when baked. In contrast, the medical community defines gluten strictly as the prolamin, or gliadin, fraction from wheat, rye, and barley. Prolamins are unique in their amino acid composition, having the highest proline and glutamine contents of all the major protein classes in these grains. The storage proteins in these cereals are all prolamins since the cereals are all members of the same family of grasses and share the same evolutionary path. Figure 1.1 shows the relationships among cereals. Common bread wheat is known to
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Fig. 1.1. Genetic relationship between gluten-containing grains and other grains.
plant taxonomists as Triticum aestivum. Spelt (T. aestivum var. spelta) shares a close genetic tie to modern wheat and is therefore reactive or toxic to celiac patients. Moving up the family tree, we find more primitive relatives of modern wheat, such as durum (T. turgidum). Even more ancient emmer and einkorn (T. monococcum), are reactive to celiac patients. Barley (Hordeum vulgare) and rye (Secale cereale) are much more distantly related to wheat but still induce the celiac response because of the presence of specific peptide sequences in their prolamins. The prolamins are named according to their source (hordeins from barley, secalins from rye, avenins from oats).
Celiac Disease Celiac disease is believed to impact 0.7% of the total U.S. population, a percentage that is similar to that found in Europe (3). The incidence of celiac disease in the non-Hispanic white population is higher than in the total population (1%). The majority of those with celiac disease remain undiagnosed. Simply stated, celiac disease is a permanent condition induced by the consumption of storage proteins from wheat, rye, or barley. The Mayo Clinic (4) defines celiac disease as a digestive condition triggered by consumption of the protein gluten…[resulting in] an immune reaction…causing damage to the inner surface of the small intestine….
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Celiac disease results in damage to the inner surface of the small intestine (Figure 1.2), greatly reducing its ability to absorb nutrients. The small intestine is the point of absorption for almost all nutrients (carbohydrates, amino acids, vitamins, and minerals) and can be considered the most important part of the gastrointestinal tract. Over time, malnourishment occurs when it is damaged. The only known treatment of celiac disease is the complete avoidance of wheat, rye, and barley (5). Even ingestion of 20–50 mg of gluten per day can prevent a full recovery in a celiac patient with damaged intestines (6). Celiac disease is an autoimmune disease, which is different than a classic allergy. In autoimmune diseases, the body’s immune system attacks its own tissues rather than protecting the body from foreign invaders. Inducement of celiac disease is not only attributable to the proteins from wheat, rye, and barley but is also the result of a combination of three major factors: genetic predisposition, reactive epitopes, and gut permeability.
Factor 1: Genetic Predisposition The immune system of those diagnosed with celiac disease is genetically predisposed to overreact (7). This genetic predisposition results in the production of proteins known as histocompatibility leukocyte antigens (HLAs). Two variants of these proteins, HLA DQ2 and HLA DQ8, are produced by 95% of celiac patients. It is estimated that 35–40% of people in Western societies have these tissue types, but currently about 2% actually get celiac disease (6). While it is nearly impossible to get celiac disease without possessing the gene for HLA DQ2 or HLA DQ8, the tissue type is common and environmental factors also are required. Additionally, there is a strong female
Fig. 1.2. Intestinal villi. Left to right: normal, partially damaged or atrophied, and fully atrophied villi in a celiac patient. (Used with permission from the Center for Celiac Research, University of Maryland School of Medicine, Baltimore)
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predisposition for celiac disease. Children of celiac patients have a 5–10% chance of contracting the disease. A twin sibling of a celiac patient has an 80% chance of having the disease, while a non-twin sibling has a 10% chance (6).
Factor 2: Reactive Epitopes The celiac autoimmune reaction is not triggered by the proteins themselves but by specific amino acid sequences in the form of small fragments of proteins called peptides. These reactive peptides are referred to as epitopes. More than 50 different epitopes in more than 100 different gluten proteins have been identified (8). They are highly resistant to breakdown by all gastric, pancreatic, and intestinal enzymes in humans and are small enough to pass through the gut into the body, Celiac disease where a complex cascade reaction occurs (9). This • is an autoimmune disease. resistance to breakdown by the body’s enzymes is • reduces absorption of nutrients. linked to the functionality of the wheat protein itself. • is induced by consumption of wheat, rye, or barley. It is believed that certain peptides are modified • affects millions of people. by the body through an enzymatic reaction, result- • is partially genetic. ing in a stronger immune reaction. Tissue transglu- • is different than wheat allergy or gluten intolerance. taminase, an enzyme found in all cells, is responsible for bonding proteins to one another, which makes it very important in the growth and repair of tissues. Transglutaminase converts the gliadin peptide into a more reactive epitope, and, in those susceptible to celiac disease, it may potentially have a negative effect.
Factor 3: Gut Permeability A third factor in celiac disease is a highly permeable gut. Celiac disease, type 1 diabetes, multiple sclerosis (MS), and inflammatory bowel diseases are all believed to be characterized by enhanced gut permeability (7). The enhanced permeability allows for peptides to more easily interact with a celiac patient’s overreactive immune system.
Symptoms of Celiac Disease Celiac disease has no typical signs or symptoms. Most people with the disease have general complaints, such as abdominal pain, bloating, intermittent diarrhea, and stools with unusually foul odor or oily consistency.
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Celiac disease may also present itself in less obvious ways, including irritability or depression, anemia, upset stomach, joint pain, muscle cramps, skin rash, mouth sores, dental and bone disorders (such as osteoporosis), and tingling in the legs and feet (neuropathy). Celiac disease symptoms can also mimic those of other conditions, such as irritable bowel syndrome, gastric ulcers, Crohn’s disease, parasite infections and anemia. Many of these conditions possess symptoms similar to the malabsorption of nutrients. Interestingly, sometimes people with celiac disease may have no gastrointestinal symptoms at all.
Diagnosis of Celiac Disease The onset of celiac disease can occur at any age. Its diagnosis is often the end result of living with the effects of the disease; however, asymptomatic people should seek testing if a relative has been diagnosed with the disease. After reviewing the health and diet, generally the first step in diagnosis is a serological antibody test (10). Such tests require that the individual still have gluten in his or her diet, and for this reason, individuals who suspect they have celiac disease should seek a medical assessment while still consuming gluten. Various antibody tests are available. The most common tests are for anti-tissue transglutaminase and for antibodies to immunoglobulins A and G. If positive serological tests indicate celiac disease, a biopsy may be performed. The biopsy helps identify the degree of damage to the small intestine. In the biopsy procedure, also called an esophagogastroduodenoscopy, an endoscope is used to collect tissue samples from the lining of the small intestine. The procedure is painless and takes less than 30 min to complete. The combination of genetic and serological tests has reduced the need for biopsies somewhat; however, the biopsy is still considered a standard test (11). HLA DQ typing may be used to determine whether a genetic predisposition is present if a diagnosis is questionable. However, to date, this type of testing is generally not covered by insurance.
Nutritional Deficiencies and Related ÂConditions Attributable to Celiac Disease People with celiac disease deal with two key issues regarding nutrition: intestinal damage that impairs nutrient absorption and the nutritional in-
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adequacy of many gluten-free products as compared with the analogous foods based on gluten-containing grains. While damage to the small intestine can be resolved through adherence to a strict gluten-free diet, the availability of gluten-free foods with adequate nutrition is often poor. The nutritional profiles of such foods need to be considered by manufacturers of gluten-free The availability of gluten-free foods products. Understanding nutritional needs is with adequate nutrition is often poor. an important aspect of gluten-free product development. Unfortunately, many gluten-free products on the market do not help alleviate the deficiencies resulting from the disease. Most of them are starch-based rather than based on whole grains containing the micro nutrient density and fiber that would be of great benefit to the celiac patient.
Fiber Fiber is specifically of concern for those with celiac disease. While many gluten-free whole grains and whole-grain flours have a higher fiber content than enriched wheat flour, most do not have levels comparable to those of whole-grain wheat flour (12). Fiber plays an important role in gastrointestinal health, so the lack of fiber in many gluten-free products serving a population with unhealthy gastrointestinal tracts is cause for concern. The average gluten-free diet is reported to provide 6 g of fiber per day (13). This is low when compared with the recommended 25 g/day for women and 38 g/day for men. While gluten-free products with added fiber are beginning to enter the market, additional fiber in celiac patients’ diets is still needed. Additionally, many of the gluten-free products on the market may lead to obesity, due to excessive caloric density from fat (14). Many gluten-free breads have higher caloric content than wheat breads of the same category (15). Several studies have shown that adherence to a gluten-free diet results in higher body mass index for both adults and children.
B Vitamins Folate deficiency might be an issue for undiagnosed celiac patients. Folate, also known as folic acid, is one of the vitamins used in wheat flour enrichment. Enriched wheat flour is one of the most important sources of folate in the North American diet, a source not available to celiac c onsumers.
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More importantly, women who are celiac patients and of child-bearing age need to ensure adequate folate intake to support growth in the developing fetus. Folate deficiency can result in neural tube defects and other complications in pregnancy.
Iron-Deficiency Anemia Iron deficiency is one of the more common conditions faced by celiac patients. The Mayo Clinic (16) defines iron-deficiency anemia as …a common type of anemia—a condition in which blood lacks adequate healthy red blood cells. Red blood cells carry oxygen to the body’s tissues. As the name implies, iron deficiency anemia is due to insufficient iron. Without enough iron, your body can’t produce enough hemoglobin, a substance in red blood cells that enables them to carry oxygen. As a result, iron deficiency anemia may leave you tired and short of breath. Malabsorption of iron can continue after the transition to a strict glutenfree diet. The morphology of the villi in the small intestine needs to be fully restored and iron in the body replenished before signs of iron deficiency subside. Incorporation of iron-rich gluten-free whole grains such as quinoa, buckwheat, teff, and amaranth can help greatly.
Lactose Intolerance A lactose-intolerant person cannot produce lactase, the enzyme that allows people to digest lactose. Lactose is a disaccharide composed of the sugars glucose and galactose found in milk Nutritional deficiencies from celiac and is produced in the cells lining the small indisease include lack of sufficient testine. Celiac disease often results in decreased • fiber production of lactase. The inability to digest lac• B vitamins tose in the small intestine leads to fermentation • iron • calcium of the sugar in the lower gastrointestinal tract, • vitamin D resulting in gas production, pain, and bloating. • magnesium Adherence to a strict gluten-free diet alleviates • lactase deficiency this issue as the morphology and functionality of the villi are restored, assuming that the celiac patient is not also truly lactose intolerant.
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Osteoporosis and Osteopenia Malabsoprtion of calcium is common in celiac patients and often leads to lower-than-normal bone mineral densities (osteopenia) or osteoporosis (17). Even after a transition to a gluten-free diet, these conditions may continue due to the time required to reverse the damage to the small intestine. Vitamin D and magnesium also play important roles in calcium absorption, so deficiencies in these micronutrients result in the prevalence of osteopenia and osteoporosis in the celiac patient. Teff and quinoa are two gluten-free grains with calcium content higher than that in whole wheat. Quinoa, buckwheat, sorghum, teff, and amaranth are all gluten-free whole grains with high magnesium relative to the amount in whole wheat.
Relationship of Celiac Disease to Other Conditions Other Autoimmune Diseases Research has shown that celiac disease is linked to other autoimmune diseases, such as type 1 diabetes and thyroid autoimmunity. The prevalence of celiac disease in type 1 diabetes patients is 10–30 times that in the normal population, and, in fact, a gluten-free diet has been shown to improve the condition of those with type 1 diabetes. MS has also been shown to be linked to celiac disease (18). One study (19) found that 11.1% of MS patients tested were also celiac patients, and all those positive for celiac disease were female (20). Additionally, the study found a high rate of celiac disease (32%) in their first-degree relatives. The frequency of celiac disease in people with autoimmune thyroid disease was 4.3% as compared with 0.4% in the control non-autoimmune population tested (20).
Autism Parents of children diagnosed with autism are increasingly turning to gluten-free diets to help alleviate symptoms of the disorder. To date, diet trials have been inconclusive in showing a link between gluten and autism (19, 21). However, neurological disorders or delays in development may be associated with nutritional deficiencies, and some in the medical community recommend that nutritional deficiencies or malabsorption be considered as a factor for those with neurodevelopmental problems.
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Dermatitis Herpetiformis Dermatitis herpetiformis is an itchy, blistering skin disease that also stems from celiac disease. Approximately 10% of celiac patients have the condition. The rash usually occurs on the torso, scalp, and buttocks. Dermatitis herpetiformis can cause changes to the lining of the small intestine similar to those of celiac disease. However, it may not produce noticeable digestive symptoms. This disease is treated with a gluten-free diet in addition to medication to control the rash.
Wheat Allergy The Mayo Clinic (22) defines wheat allergy as …an allergic reaction to foods containing wheat….Wheat allergy may sometimes be confused with celiac disease, but these conditions are different. A wheat allergy generates an allergy-causing antibody to proteins found in wheat. But, one particular protein in wheat—gluten—causes an abnormal immune system reaction in the small intestines of people with celiac disease. Celiac disease is often erroneously referred to as an allergy to wheat gluten; however, there are distinct differences between the two. In wheat allergy, the cause is less specific, and the allergic response results in the production of antibodies that attack the foreign proteins, rather than the autoimmune response that attacks the body’s own tissues in those with celiac disease. As compared to food intolerance, the allergic response can impact many tissues, while food intolerance is for the most part limited to the digestive system. As with other food allergies, the rapid onset of severe reactions such as anaphylaxis can result from the ingestion of minute quantities of the allergen. Anaphylaxis can cause difficulty in breathing and reduce blood pressure. Milder symptoms can include swelling or itchiness in or on the mouth, tongue, lips, or throat. Allergic reactions can also manifest themselves as vomiting, abdominal cramping, and diarrhea.
Gluten Intolerance Gluten intolerance is more common than celiac disease. Some research suggests that gluten sensitivities or intolerance are six times more common than celiac disease (23). Gluten intolerance relates to several conditions in