Vol. 2, #10
March 12, 2005

Q: What is gluten allergy to grains and how is this related to Coeliac disease? - Technical

A: Coeliac disease (also known as celiac disease (CD), coeliac sprue, or gluten-sensitive enteropathy ) is a condition of the small intestine. Gluten, a substance found in barley, oats, rye, and wheat reacts with the small bowel, causing damage by activating the immune system to attack the delicate lining of the bowel, which is responsible for absorbing nutrients and vitamins.

If left untreated, coeliac disease can lead to anemia, bone disease and, rarely, some forms of cancer. The most important treatment is avoiding all food that contains gluten. This usually results in improvement, or even disappearance, of the damage to the lining of the bowel. However, the damage will recur if gluten is reintroduced into the diet.

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Figure 1: Healthy villi of the small intestine (as seen under the microscope).
© NetDoctor
Figure 2: Damaged villi of the small intestine.

Gluten is a mixture of two proteins, gliadin and glutenin. When mixed with water it becomes sticky and so forms the familiar texture of dough made from wheat and rye flour. When gluten comes into contact with the lining of the small bowel, a reaction occurs, where the immune system mistakenly attacks the lining of the bowel as if it was a 'foreign' organism. The small bowel has 'villi, which are tiny finger-like projections, visible under the microscope (see Figure 1). They provide a large surface area, over which we absorb nutrients, such as vitamins, folic acid, iron and calcium. In coeliac disease these are attacked by the immune system, (see Figure 2) and are eventually destroyed (see Figure 3). This results in nutrients in food going down the gut without being absorbed (malabsorption), leading to vitamin and mineral deficiencies, anemia and thin bones (osteoporosis).

A definite risk factor to developing coeliac disease is a history of the condition in your family. Coeliac disease occurs in people who are genetically prone to it - ie. it 'runs' in families. If you have a parent, sibling or child with coeliac disease, you have a 10 per cent chance of also developing it. If you have an identical twin with coeliac disease, your chances are increased to more than 70 per cent.

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Figure 3: Villi completely destroyed by the immune system. All pictures courtesy of Prof PJ Ciclitira.

Coeliac disease has many and varied symptoms, and adult symptoms are different from those of children.

In childhood the symptoms do not appear until gluten-containing foods are introduced into the diet. First symptoms usually include becoming irritable and miserable, with a poor appetite and failure to gain weight. Stools (bowel motions) can become pale, bulky and smell nasty. Some children start with vomiting and diarrhea, so they are often given the wrong diagnosis of 'gastroenteritis'. The stomach may become swollen, and the muscles of the arms and legs become wasted and thin.

In adults the symptoms may be similar, including weight loss with pale, offensive diarrhea, or constipation and abdominal bloating with 'wind'.  Half of adults with coeliac disease do not have any symptoms from the bowel. They approach their doctor because of extreme tiredness, psychological problems like depression, bone pain and sometimes even fractures (due to thinning of the bones), ulcers in the mouth or a blistering, itchy skin rash mostly on the elbows and knees (called dermatitis herpetiformis).

Some women with coeliac disease have difficulty getting pregnant, and may be diagnosed because of this. Recurrent miscarriage (spontaneous loss of a pregnancy) is sometimes associated with coeliac disease. Some women are diagnosed during pregnancy because their bowel cannot absorb enough iron and vitamins to keep up with the demand of being pregnant, making them severely anemic. Babies who are small for their age in the womb (intrauterine growth retardation) are more frequently born to mothers with coeliac disease.

There are other rare conditions, which although found in the general population, occur more frequently in people with coeliac disease. These conditions usually require referral to a hospital specialist. They include autoimmune diseases (where the immune systeminadvertently attacks the body) such as thyroid disease, insulin-dependent diabetes and a condition that affects the liver called primary biliary cirrhosis.

Strong evidence suggests an inherited predisposition to celiac disease. It occurs up to 100 times more frequently in first-degree relatives of patients with the disease than in the general population. Studies of identical twins have shown a disease concordance of 70%. This inherited susceptibility is closely associated with HLA-B8, HLA-DR3, and HLA-DQ alleles. The alleles encoding DQW2 are in linkage disequilibrium with B8 and DR3. More than 90% of celiac patients possess the HLA-DQW2 allele, but the nature of the pathogenetic connections between the HLA type and gluten sensitivity remains unclear. Seventy percent of unaffected siblings have the same HLA-DR phenotypes as their affected sibling, so some additional genetic or environmental factors appear necessary for gluten sensitivity to be manifest.

At a symposium in Finland, a collaborative study done jointly in Galway, Ireland and Alabama, USA provided some new information.  A series of families from the Galway group were studied.  A new method of looking for gene site associations was used.  Some of the chromosomes from blood samples of these patients were studied ford for genetic similarities.  [Human beings have 23 pairs of chromosomes.  Each chromosome is composed of a multitude of genes.] They found one spot on chromosome #6 which it seemed to be very highly associated with CD; in other words, those that have CD seem to have
this "spot" on chromosome #6; those that did not have CD did not tend to have this "spot".  It is not known what the genes in that "spot" do, because it is one of those uncharted areas of human genetics.  It is hoped that over the next two years we will learn which specific gene is involved and how it confers a risk for CD.  So there are probably at least two separate genes that come together to result in a genetic predisposition towards CD.

Gluten is a component of barley, oats, rye, and wheat, all of which belong to the species Triticum aestivale. Gliadin, the toxic agent in gluten, is rich in proline and glutamine, hence the term prolamins for alcoholic extracts of gluten. Several subfractions of gliadin are known, the best studied being, , , , and . These have in turn been subfractionated, and all the gliadin moieties appear harmful to the intestinal mucosa.

The causal relationship between dietary gluten and mucosal changes in susceptible patients is unquestioned; however, many questions remain regarding the mechanism whereby gluten exerts its harmful effects. Initially, it was suggested that incomplete brush border hydrolysis of gluten as a consequence of enzyme deficiency led to the formation of toxic products, but inability to demonstrate abnormally low mucosal peptidase or carbohydrase activity following treatment with a gluten-free diet rendered this hypothesis untenable.

A significant structural amino acid homology between a gliadin fragment and a non-structural component, E1B of type 12 adenovirus has been noted. These investigators suggested that adenovirus infection of susceptible subjects brings about gluten sensitization through the process of molecular mimicry. Although this group found a significant increase in the prevalence of antiadenovirus 12 antibodies in patients with untreated celiac disease, other workers have failed to confirm this finding. The polymerase chain reaction technique using primers specific for the EB1 gene showed no evidence for persistent adenovirus infection in celiac disease.

A variety of antibodies directed against both dietary and self antigens have been found in serum and intestinal secretions of celiac patients. Antigliadin IgA antibodies are found in up to 90% of untreated celiac patients, and their liter gradually diminishes on gluten withdrawal. Other food-related antibodies such as antiovalbumin and anticasein have been described. It appears likely that antibody production is related to the increased paracellular intestinal permeability found in coeliac disease. Although pathogenic mechanisms involving disordered immunity have been proposed, such as antibody-dependent cell-mediated cytotoxic effects and immune complex formation, the role of antibodies in causing villous damage remains conjectural.

IgA antibodies directed against specific tissue components have also been identified. These include antireticulin, antijejunal, and antiendomysial antibodies, which can be detected by immunofluorescence techniques in both human and animal tissues. Antijejunal and antiendomysial antibodies likely recognize a common antigen. The endomysium is a delicate connective tissue layer surrounding intestinal smooth muscle, and antiendomysial antibodies have been found in more than 95% of patients with coeliac disease. The antibody specificity of both antiendomysial and antigliadin antibodies is 90%. Antiendomysial antibody liters decrease after institution of a gluten-free diet. Measurement of antibody liters has been suggested as a screening test for coeliac disease and as a means of evaluating dietary compliance in unresponsive patients.

The presentation of celiac disease is variable, ranging from mild, nonspecific features through monodeficiency states to a full-blown classic panmalabsorption syndrome. The classic form of the disease is now the least common presentation, and several authors have emphasized the need to consider celiac disease in patients with irritable bowel-like features occurring in association with another trigger finding such as anemia, weight loss, or a monodeficiency state.

Diarrhea is found in 70% of patients. It is usually intermittent, occurs three to four times daily, and is of mushy consistency. Celiac patients often have crampy abdominal pain that, in association with diarrhea and bloating secondary to fermentation of lactose and other sugars.

Your GP (General Practitioner) may ask you for a history of your symptoms. This may include questions about the frequency and color of your bowel motions, but there is no need to feel embarrassed about this. They may also want to know whether you have lost weight or whether you have symptoms of anemia (tiredness, exhaustion, pallor). The doctor may examine your abdomen, or look for the blistering rash on your skin, and check for mouth ulcers.

Blood tests are usually the first investigation. Your doctor will check for anemia, testing the levels of iron, folic acid and calcium in your blood. Another blood test detects antibodies (part of the immune system) commonly, but not always, found in coeliac disease. Several different types of antibodies are associated with coeliac disease but the most specific is called 'anti-endomysial' antibody. If this is present in the blood, then you are very likely to have coeliac disease.

However, an endoscopy test - with a biopsy of the small bowel lining - is required for a definite diagnosis to be made. Your doctor should arrange this test at the Endoscopy Unit at your local hospital. You can usually choose to have the test under general anesthetic (put to sleep) or have a local anesthetic (numbing the throat with a spray). Then a tiny camera on the end of a thin flexible tube is put into the mouth and is guided down the esophagus (gullet) into the stomach and then the small bowel. A small piece of the lining of the bowel can be removed (called a biopsy) - you will not feel any discomfort. The whole procedure will take about 10 minutes. The biopsy specimen will be sent to the laboratory where it can be examined under a microscope to check on the size and shape of the villi. This will usually confirm the diagnosis. It is usual to have this test repeated after several months on a gluten-free diet, to check that the lining has recovered.

Although coeliac disease is not preventable, sticking to a gluten-free diet can reverse damage to the small intestine. This requires considerable discipline. Gluten occurs in bread, biscuits, cakes and pastries, pasta, breakfast cereals and is also used in some manufactured soups and sauces. Gluten is also 'hidden' in some foods such as crisps and similar snacks, as well as chips in restaurants. Cooking oil (or mixed vegetable oil) can contain wheat-germ oil, so use sunflower or olive oil instead. Malt vinegar, soy sauce, mustard and mayonnaise contain gluten. Beer and whisky are made from grain containing gluten, but other alcoholic drinks, such as wine or cider are gluten-free.

Of course, many foods do not contain gluten, including all fruits, salads and vegetables, rice, maize, sweet corn, nuts, potatoes, red meat, chicken, fish, eggs and dairy products.

It is probably best to avoid oats as they may contain a small amount of gluten. Oats have generally been shown not to upset people with coeliac disease. However, most oats are milled and stored in the same mills as wheat and are probably contaminated with gluten.

There are excellent books available on gluten-sensitivity, including general guides and recipe books.

Some medicines contain gluten, so you must check with your doctor or pharmacist.

Gluten-free foods are available with or without a prescription from your doctor or pharmacy. Your pharmacist can advise on the range of prescribable gluten-free products. These include gluten-free flour, breads, biscuits and pasta. These should be used as a substitute for the normal gluten-containing varieties. Your GP should also refer you for a consultation with a dietitian, who can give you diet sheets and advice.

Another important aspect of treatment is replacing vitamins and minerals. You may need iron tablets, folic acid supplements (especially when pregnant or planning to get pregnant) and calcium.

Very severe coeliac disease, which does not get better on a gluten-free diet, may need tablets that 'damp down' the immune system, such as steroid tablets, but this is very rare.

There are no known severe risks of treatment. However, gluten-free food does tend to be low in fiber and can cause constipation in some people. To counteract this, take plenty of fruit and vegetables. If the problem persists, try rice bran or a laxative called Fybogel, which is available with or without a prescription from your pharmacy.

What are the consequences of no treatment?
Not taking a gluten-free diet will cause the symptoms to persist, including diarrhea, weight loss and anemia.

Complications of coeliac disease are rare. They include infertility in women, difficulties during pregnancy, autoimmune diseases (thyroid disease, diabetes and some types of liver disease), thinning of the bones (osteoporosis). There is a slightly increased risk of developing bowel cancer. However, a gluten-free diet reduces all these complications, as well as associated conditions such as dermatitis herpetiformis and mouth ulcers.

Studies have shown that sticking to a gluten-free diet for five years or more reduces the risk of all cancers associated with coeliac disease to that of the general population.

A gluten-free diet should enable the lining of the bowel to return to normal in most people. So the disease can be 'curable', but only by avoiding foods that contain gluten. You can enjoy a good quality of life without symptoms or long-term complications.

However, most food items can satisfactorily be replaced by similar products made using wheat-free flours (flour mixes work best). To make baked goods rise better, mix baking powder or soda with liquid in the recipe before adding it to other ingredients. There are a lot of alternatives to wheat flour available. Some of these contain gluten and are therefore not suitable for anyone with coeliac disease or sensitive to gluten. They are marked with an asterisk (*).

  • amaranth flour is produced from ground seeds. It is high in protein, calcium and iron and is best combined with a high starch flour such as tapioca and potato for baking. Amaranth has a nutty flavor. If puffed it can be used as a breakfast cereal. Arrowroot is a starchy root and useful as a thickening agent in puddings, cakes and sauces
  • barley* has a mild flavor, but a heavy texture and does not rise well. Barley flour can be used for cakes, cookies, muffins and pies
  • buckwheat, despite its confusing name, is suitable for people with wheat allergy. This flour, which has a strong and distinctive flavor, combines very well with other flours in pancakes, muffins, pasta and bread. Buckwheat is rich in Vitamin B
  • cornflour is a good thickening agent. It may be used in baking cakes, biscuits and bread and is the essential ingredient for polenta. Make sure you purchase maize cornflour and not wheaten cornflour, which contains gluten
  • millet is a member of the grass family and has good nutritional value, providing vitamin B, iron and other minerals. It is available as a grain, a flake or a flour and can be used in a variety of sweet and savory dishes. Although gluten free, millet may cause problems for people sensitive to gluten
  • oats* have a good nutritional value and make an excellent breakfast cereal in porridge and muesli
  • potato flour is an excellent thickening agent and useful for baking. It is a pure starch with little flavor of its own and works well in bread recipes, cookies and cakes, pasta and pizza bases, when combined with other flours
  • quinoa (pronounced "keen wa") is a seed with a mild nutty flavor. It is high in protein, vitamin B and E and fiber. Quinoa can be combined with rice in making risotto and pilaf. Rice flour, rice flakes and ground rice can be used in baking biscuits and making puddings. When combined with other flours it also works well to make bread, pasta and pastries
  • rye* flour is quite heavy (it doesn't rise very well) and has a strong flavor Rye is mainly used for baking bread. You can combine it very good with other flours
  • sago comes from the trunk of the palm tree and is a good thickener for desserts with no strong flavor
  • soya flour has a strong flavor but is good combined with other flours. It is a good source of protein (with a great value), fat and vitamin B
  • spelt* (dinkel) is an ancient wheat, and should be avoided by those with wheat allergy. It also contains gluten, so is not suitable for those with coeliac disease. (Note: some people with wheat allergy may be able to tolerate spelt, check with your specialist for skin prick testing to spelt before trying this grain.)
  • tapioca comes from the root of a tropical plant and is almost pure starch. It is useful for making puddings, fruit pie fillings, custards, soups and stews
  • xanthan gum is produced by culture fermentation of glucose. It has the ability to hold foods together, this makes it a good stabilizer as a substitute for gluten in breads
  • yam flour is high in starch and can be used in casseroles, soups and for baking. Wheat is a good source of carbohydrates, fiber and vitamin B1. You can get these nutrients by eating any other grains mentioned above; the nutritional benefit of the different grains is quite similar.

In short, avoidance of gluten-containing grains is a permanent and life-long requirement for a healthy life for people with coeliac disease as of this writing.

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DISCLAIMER:  The information in this column, is NOT intended to diagnose and/or treat any health related issues and is provided solely for informational purposes only. Consult the appropriate healthcare professional before making any changes to your healthcare regime. Even what may seem like simple changes in the diet for example, can interact with, and alter, the efficiency of medications and/or the body's response to the medications. Many herbs and supplements exert powerful medicinal effects. Neither the author, nor the website designers, assume any responsibility for the reader's use or misuse of this information.

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