WHAT IS GLUTEN?
Gluten is the dough-forming protein fraction of wheat flour. It is primarily responsible for the texture, flow, and elasticity properties of wheat dough. Wheat flour contains between 7 and 12 percent gluten proteins by weight.1 The physical properties gluten imparts on finished
products and the low cost of wheat flour have made wheat-based products the most widely accepted and available cereal products in the world.
Gluten absorbs twice its weight in water and imparts a chewy texture to finished products. Gluten proteins are readily digestible, which makes gluten a desirable protein source in manufactured food. It also may improve flavor and shelf life of products.1 In the past, gluten was found only in foods containing wheat. Food manufacturers have found ways to separate the gluten fraction, however, and it is now used in a wide variety of processed foods. For example, gluten is added to pizza dough to improve texture, to sausage and canned meat products as a protein extender, and to processed cheese to give the product more elasticity.
Overall, gluten is used to enhance the properties of many manufactured foods, and it has been widely adopted to increase the quality and lower the cost of prepared foods. While the increasing use of gluten in food manufacturing has improved quality at a lower cost for some, it has made gluten-free food more difficult to find for those individuals unable to tolerate gluten.

GLUTEN INTOLERANCE
Gluten intolerance is a general term describing conditions characterized by sensitivity to gluten. The most common gluten intolerance is celiac sprue, also called coeliac disease, nontropical sprue, and gluten-intolerant enteropathy.(2) Celiac sprue is characterized by small bowel mucosal atrophy. In celiac sprue, the villi of the small intestine (finger-like extrusions in the epithelial wall) become flattened.(3) Since the major biological function of these villi is to absorb vitamins, minerals, and other nutrients during digestion, their disruption can lead to nutritional deficiencies and intestinal dysfunction. Celiac sprue has been reported to occur at a frequency of 1 in 1000 individuals, although more recent reports in which subclinical celiac sprue has been more readily identified suggests it may occur in 1 in 300 individuals(2)
Symptoms of celiac sprue include malabsorption of nutrients, weight loss, fatigue, edema, abdominal distension, diarrhea, headache, nausea, muscle cramps and spasms, and joint pain.(4) More severe symptoms may also manifest as infertility, neurological disturbances, and bone wasting. It has been reported that as little as 0.1 grams of ingested gluten can trigger symptoms. Strict, life-long adherence to a gluten-free diet is the basic treatment for celiac sprue.
Celiac sprue is a cell-mediated intolerance to gluten that involves T-cells of the immune system.2,3,4 IgE- and IgG-mediated gluten allergies are distinct from celiac sprue and manifest with different symptoms such as constriction of the bronchi in the lungs, skin rashes, itching,
sore eyes, headache, and other common allergic symptoms. Gluten intolerance may also result in dermatitis herpetiformis, a blistering that occurs when granular IgA is deposited under the skin.5 Dermatitis herpetiformis is a less severe form of celiac sprue, but research studies suggest that about 75 percent of patients who display dermatitis herpetiformis may also have small-bowel villous atrophy.4 Why some patients respond to
gluten with dermatitis herpetiformis and others respond with small-bowel mucosal atrophy is unknown.

DO OTHER GRAINS CONTAIN GLUTEN?
By definition, gluten is found only in wheat, although the term is commonly used to refer to any grain protein harmful to sensitive populations. Like other proteins, gluten is made up of smaller subunits called polypeptides, which group together to form large protein complexes. The two polypeptide components of gluten are the gliadins and glutenins. Gliadins are monomeric (single) polypeptides that give wheat dough its flow characteristics, and glutenins are polymeric (multiple) polypeptides that lend elasticity to finished wheat products.6 Gluten is roughly half gliadins and half glutenins.
Recent investigations into the nature of gluten intolerance have implicated a specific amino acid sequence found in gliadin as primarily responsible for the sensitivity to gluten.7 The gliadin fraction of gluten is also called prolamin, since it contains some sequences high in the amino acid proline. Although gluten occurs only in wheat, many clinicians refer to a gluten-free diet as one in which wheat, triticale, rye, and barley are avoided, since individuals with celiac sprue react to rye, barley, and triticale as well as wheat. Barley and rye do not contain gliadin, but they do contain prolamins that are structurally similar to wheat gliadin.8, 9 Triticale is a hybrid of rye and wheat. The similarity in protein sequences between the prolamin proteins in these grains may account for the sensitivity to rye, barley, and triticale shown by gluten-intolerant individuals. Clinical observations have suggested that gluten-sensitive individuals may also respond to oats, but this issue remains controversial. Several recent studies have reported that oats are safe for consumption by celiacs. In one study, intestinal biopsies showed no damage in 92
individuals with celiac sprue after one year of a diet of 50 grams of oats every day.10 Oats contain one fifth as much prolamin as rye or wheat, which may explain this observation. However, most commercial oat products contain wheat flour or gluten. In addition, due to
the sharing of equipment at grain processing plants and the rotation of crops, in which wheat may be grown on the same field as oats, contamination of oats with wheat may occur. Therefore, contamination of oat products with wheat may account for the adverse response to Oats often reported by gluten-sensitive individuals.
Unfortunately, the term gluten has also been used quite frequently to describe other grain proteins or properties. For example, corn proteins have been described as “corn gluten.” Corn does not appear to initiate or exacerbate a gluten intolerance, although allergies to corn proteins may occur. Rice has also been referred to as “glutinous,” but in this case, the term“glutinous” refers to the stickiness of the rice, not its gluten content. Rice and barley do contain proteins structurally similar to glutenin but not gliadin,11 although no reports have documented a gluten-intolerant or allergic reaction to these specific proteins.(4)

RECOGNIZING CELIAC SPRUE
Celiac sprue was first described in the 1940s, and although the clinical management of celiac sprue is well established, it has become apparent over the past decade that much remains to be learned about the clinical recognition of celiac sprue. The diagnostic criteria for celiac sprue, which were established in 1990 by the European Society for Pædiatric Gastroenterology and Nutrition (ESPGAN), require a small-bowel biopsy to demonstrate deterioration of the villous morphology of the small intestine as well as remission of symptoms on a gluten-free diet.4 In symptom-free patients, a second biopsy is required after treatment with a gluten-free diet to establish improvement in small bowel mucosa.
Individuals with celiac sprue often show presence of antibodies to gluten, and gluten-antibody tests have been proposed as a screening tool for celiac sprue.12 The presence of gluten-responsive antibodies and their disappearance after a gluten-free diet support the diagnosis but are not
necessary, since celiac sprue may occur in the absence of circulating antibodies. Intestinal impermeability tests have also been used to screen for possible celiac sprue. Research studies have shown that this test may be useful in screening large populations or as a low-cost initial
screen for celiac sprue.13
Celiac sprue appears to run in families and has been associated with an HLA-DR3/DQ2 genotype.4 However, research suggests this genotype is only a risk factor and not deterministic for the condition of gluten intolerance. The manifestation of celiac sprue appears also to
require a trigger; and a change in diet, viral infection, or even stress have all been suggested to play a role in etiology of celiac sprue. Insulin-dependent diabetes mellitus is also associated with the HLA-DR3 genotype and, accordingly, a higher percentage of celiac disease is found
among IDDM patients than in the general population.14 Patients with selective IgA deficiency, autoimmune thyroid disease, Sjøgren’s disorders, alopecia areata, or Addison’s disease have also been found to have an increased risk of celiac disease.2,4,14

A GLUTEN-FREE DIET
At the present time, there is no cure for gluten intolerance. Individuals with this condition must adopt a lifelong diet of gluten-free food. When followed correctly, individuals with celiac sprue respond quite favorably to a gluten-free diet. Research suggests, however, that only 50
to 70 percent of individuals with celiac sprue maintain a strict gluten-free diet, and poor compliance is considered the main reason for a poor response to treatment.4
Even when the individual with celiac sprue is compliant with dietary restrictions, the glutenfree diet is, for a variety of reasons, becoming increasingly difficult for celiac sprue patients to follow. Foods labeled “gluten free” may be contaminated during processing or packaging
at plants that use the same equipment to process both gluten-containing foods and foods that are designed to be gluten free. Some products may contain other sources of gluten than grain flour, such as wheat germ, alcoholic beverages milled from wheat or barley, pharmaceutical
products, condiments, and vinegar. These products use fiber and carbohydrates from grains, Another area of confusion is the definition of gluten free. The Codex Alimentarius standard (118-1981) defines a diet as gluten-free when “the total nitrogen content of the gluten-containing cereal grains used in the product does not exceed 0.05 g/100 g of these grains on a dry matter basis.” Therefore, some products may be labeled gluten free even when they contain wheatbased ingredients. For example, wheat starch, which generally contains less than 0.04 g gluten
per 100 gram starch, has been shown to be safe in celiac sprue patients.4 However, some individuals may be sensitive to these small levels of gluten. The individual with celiac sprue must become diligent in reading the labels of food products carefully for possible presence of
gluten, and he or she must be able to determine when wheat-, rye-, or barley-based ingredients might be harmful.

REFERENCES:
1. deMan JM. Principles of Food Chemistry. 2nd ed. New York, NY: Van Nostrand Reinhold; 1990:132-134.
2. Skerritt JH, Devery JM, Hill AS. Gluten intolerance: Chemistry, celiac-toxicity, and detection of prolamins in foods.
Cereal Foods World. 1990; 7:638-643.
3. Marsh MN. Transglutaminase, gluten and celiac disease: Food for thought. Nature Med. 1997; 3:725-726.
4. Markku M, Collin P. Coeliac disease. Lancet. 1997; 349:1755-1759.
5. Savilahti E, Reunala T. Is dermatitis herpetiformis a gluten-sensitive enteropathy? Int J Dermatol. 1990; 29:706-708.
6. Hargreaves J, Popineau Y, Le Meste M, Hemminga MA. Molecular flexibility in wheat gluten proteins submitted to heating.
FEBS Letters. 1995; 372: 103-107.
7. Saltzman JR, Clifford BD. Identification of the triggers of celiac sprue. Nutr Rev. 1994; 52:317-319.
8. Bushuk W. Rye: Production, Chemistry, and Technology. St. Paul, Minn: American Assoc. of Cereal Chemists; 1976:92-95.
9. Ellis HJ, Doyle AP, Day P, Wieser H, Ciclitira PJ. Demonstration of the presence of coeliac-activating gliadin-like epitopes
in malted barley. Int Arch Allergy Immunol. 1994; 104:308-310.
10. Janatuinen EK, Pikkarainen PH, Kemppainen TA, et al. A comparison of diets with and without oats in adults with celiac
disease. New Eng J Med. 1995; 333:1033-1037.
11. Ellis HJ, Doyle AP, Wieser H, Sturgess RP, Day P, Ciclitira PS. Measurement of gluten using a monoclonal antibody to a
sequenced peptide of ß-gliadin from the coeliac-activating domain I. Biochem Biophys Methods. 1994; 28:77-82.
12. Rautonen J, Rautonen N, Savilahti E. Antibodies to gliadin in children with coeliac disease. Acta Pædiatr Scand. 1991;
80:1200-1206.
13. Juby LD, Rothwell J, Axon ATR. Lactulose/mannitol test: An ideal screen for coeliac disease. Gastroenterology. 1989;
96:79-85.
14. Cronin CC, Shanahan F. Insulin-dependent diabetes mellitus and coeliac disease. Lancet. 1997; 349:1096-1097.