Malabsorption Syndromes and Celiac Disease

Paul Reller, L.Ac.

Certain individuals may inherit the tendency, or otherwise develop, an inability to digest certain common food nutrients, sometimes causing deficiencies or reactions that are a serious threat to health. Research still has not produced clear information to fully explain most of these syndromes, but does give us enough information to at least change our dietary habits and utilize Complementary and Integrative Medicine to correct many of these serious disorders, such as Celiac disease, that arise from gastrointestinal dysfunction and malabsorption of various nutrient chemicals.

Malabsorption syndromes, such as gluten and lactose intolerance, are difficult to diagnose, varied in presentation, and range from a simple health problem to a complex syndrome of diseases. Each patient must be individually analyzed and a proactive approach on the part of the patient, with a clear understanding of the potential complexities of these problems, and realistic means of objective diagnosis, is very important when the health problems may be difficult to objectively diagnose and varied in presentation.

Celiac Sprue, or Celiac disease, is one of the problems that may occur when the body is unable to digest gluten & gliadin proteins properly. The term sprue refers to a malabsorption syndrome, while the term Celiac disease may also refer to a host of symptoms and associated diseases seen eventually with syndromes of gluten and gliadin malabsorption, or sprue. Gluten is found in wheat, oats & barley, as well as malt, grain starch thickener, vitamin fillers, soy sauce, meat substitutes, and stabilizers in ice cream, ketchup, etc. Elimination of these proteins from the diet, as much as possible, substituting corn, rice and other grains, is both part of the cure and perhaps the only clear way of diagnosing the disorder, with observation of symptom elimination. Diagnosis with testing for antibodies and other markers, and then proceeding to a small intestine biopsy with enteroscopy, is not entirely accurate in all cases, and this is explained more fully below. Clearing of symptoms with the elimination of the sources of gluten and gliadin in the diet listed above is perhaps the most accurate way to insure diagnosis. These food items should be nearly eliminated from the diet for 6 months to evaluate. Long-term avoidance of gluten and gliadin may not be necessary if a comprehensive treatment protocol is used to clear the various underlying mechanisms of gluten malabsorption and the dysfunctional immune responses that may occur with this malabsorption and accumulation of gluten and gliadin peptides in the small intestine lining.

Complete elimination of glutens from the diet is not so simple a task for many individuals. The most problematic form of gluten is commercially altered high gluten content flour and filler. These glutens may be in items that one would not usually consider wheat. For instance, a McDonald's hamburger has a fairly high content of gluten, as well as soy flavoring that contains gluten, and almost all lunch meats contain gluten. Almost all snack foods contain gluten as well, even candies and chocolate bars. Many commercial dairy products contain gluten, using modified food starch as a thickener for cottage cheese, buttermilk, sour cream, and ice cream, as well as cheese snacks, and shredded cheese, which is coated with a fine gluten flour to prevent sticking. These modified gluten starches and fillers, and high gluten content flours in the commercial food industry, are perhaps the most pathological types of gluten, harder to digest fully, more reactive to our immune responses. Commercial vinegars, found in many products, are often derived from wheat, and many commercial salad dressings, mayonnaise, mustards, and catsups contain modified, or altered glutens. Most pharmaceutical medications contain gluten fillers, and many drug store items, such as laxative, contain glutens. The industry has responded to public demand by creating more gluten-free items, but FDA enforcement of nutrient labeling and claim is extremely lax, and the industry is well awary of this. There are now many documentaries showing how gluten-free food items were tested and showed a gluten content. The fact that so many commercial foods, or all types, contain altered or modified glutens, should make the public realize where this high immune reactivity and malabsorption problem came from.

Understanding how gluten and gliadin malabsorption and immune reactivity occurs

This problem is inherited in 10% of close relatives and seems related to certain genes or epigenes in some cases, but debate still goes on as to the actual mechanism of disease. It could be an autoimmune-like reaction where the body’s T cells attack certain proteins in the intestines, or it could be an allergic reaction created by irritation in the intestine when digesting these proteins, triggered during a period of intestinal infection. It could be either, or both, depending on the case. T-cell responses in the initial phase of the disease may stimulate B-cell and macrophage responses that perpetuate aspects of the disease. Thus, both the innate and acquired immune responses may be involved. Each case should be analyzed individually, as different individuals may have different underlying causes and manifestations of the disease. One specific test for an autoimmune type of reaction to glutens is a blood test for antibodies to an individuals own enzyme anti-TG (transglutaminase). The test will be positive only if the patient is still eating gluten. A negative test does not rule out reaction to gluten and gliadins. Often, the patient suspects gluten malabsorption and stops eating gluten before the test is administered. There are also false negatives with the test, where the patient has Celiac disease but has not produced enough antibodies to transglutaminase. This is why a more thorough testing is recommended to more definatively diagnose Celiac disease. Other common blood tests include those for anti-gliadin IgA and IgG. Here too, negative tests do not rule out reaction to gluten or celiac disease, but positive tests indicate allergic reaction, although these positive tests are not always indicative of a reaction to gluten and gliadin. An endoscopic biopsy of the small intestine lining, or membrane, is then studied to confirm the signs of actual Celiac disease. To stop hyperreaction to glutens, it is recommended that you avoid glutens in the diet as much as possible for 6 months or more. This may confirm Celiac disease, but correction of the underlying health problems, and in advanced cases, associated health problems, requires more than just avoiding gluten in the diet.

The result of celiac sprue is ill health of the stomach and small intestine mucosa, with inability to absorb many nutrients and to stimulate digestive secretions from the pancreas and gallbladder. This usually also causes an inability to properly digest fats, and anemia, with many white blood cells (lymphocytes), as well as red blood cells, attracted to the intestinal lamina, and lost to the circulating blood. Anemia may also be caused by a deficiency of a dipeptidyl peptidase that is almost always deficient in Celiac disease, and is also integral to hormonal stimulation of blood production. The condition of celiac sprue may appear mild enough and unnoticed for years and then become severe during periods of GI infection or other stress, often causing problems during childhood but somewhat under control during the adult life. There are many possible symptoms. Serious symptoms usually bring the patient to the attention of specialists, but the difficulty in diagnosing causes many individuals to go through life undiagnosed, especially as celiac sprue and Celiac disease may be episodic.

Understanding the variety of symptoms and presentations that are possible with gluten malabsorption and Celiac disease

Clinical presentation in Celiac disease, or sprue, is greatly varied, depending on the extent of the mucosal disease. Subclinical syndromes, meaning syndromes of health problems that do not present as a typical clinical disease, are most common with gluten and gliadin malabsorption and early Celiac disease. These presentations are often unclear. A patient may proceed with treatment and avoidance in these cases and observe the results. Treatment in Complementary Medicine is not harmful, has no side effects, and usually provides health benefits even for those without true gluten maabsorption and Celiac disease.

Typically, symptoms in clinical cases, meaning cases where typical clinical symptoms and signs are evident, present crampy abdominal discomfort, chronic diarrhea, bloating, weight loss, and fatty stools (steatorrhea). Iron deficiency syndromes are common, as well as easy bruising (deficiency of vitamin K). Peripheral neuropathies are frequently associated (deficiency of vitamin B12), and osteoporosis (deficiency of vitamin D2 and calcium). Restoration of these deficiencies should focus on restoring a healthy intestinal mucosa and GI function to restore proper absorption. Taking of supplements may not work, as the supplements themselves need to be absorbed. Common iron supplementation may worsen the symptoms in the gastrointestinal tract. Herpes syndromes may be worsened due to IgA deposition in the skin and IgA antibodies produced by the disease. Small intestinal lymphoma risk is increased. Endoscopy and blood tests are very important in the diagnosis. A combination of biopsy, with presence of anti-gliadin antibodies (IgA and IgG), anti-endomysial antibodies (IgA), and tissue transglutaminase antibodies, are the basic standard diagnostic protocol. These tests should be administered before starting treatment with the Complementary Medicine physician, ideally. Basic treatment involves a 6 month avoidance of glutens and gliadins while working with the Complementary Med physician, and supplementation with liquid Vitamin D3 and B12, vegetarian iron supplement formula, and vitamin K2, is highly recommended as a start. Avoidance of alcohol, antibiotics, NSAIDS, and laxatives during the treatment, all of which may contribute to malabsorption, is recommended. Avoidance of refined sugars and carbohydrates, as much as possible, is also recommended. If a comprehensive step-by-step protocol is utilized, the quickest successful outcome is achieved. This is highly recommended.

In young patients with iron deficient anemia without GI bleeding, celiac sprue is strongly considered, especially when the immediate family has a history. This shows that there is a strong correlation between celiac sprue and microcytic anemia. Since there are a number of types of anemia, tests must confirm a differential diagnosis to be sure that you have an iron deficient, or microcytic, type. Copper deficiency also occurs in celiac disease and contributes to anemia and other problems. Copper is necessary for absorption of iron and even a mild copper deficiency impairs both iron absorption and red blood cell health, as well as the ability of white blood cells to fight infection. Copper supplementation should be in the form of copper amino acid chelate, and to assimilate copper you must balance the intake with zinc and take folic acid. To avoid competition in absorption, take the 2.5 mg copper chelate about 2 hours after you take OptiZinc (zinc monomethionine) and folic acid. Copper levels are higher in women than in men and a deficiency of copper in relation to zinc may contribute to subclinical hypothyroidism, mental and emotional problems, and chronic pain syndromes, especially if the joint tissues are inelastic. Even in adults the prevalence of microcytic or iron deficiency anemia is highly associated with celiac disease.

Adult celiac disease may be much more prevalent than is evident. It is thought that a viral illness is often needed to initiate the disease, or increase the antibody response. The adult with celiac sprue, or gluten and gliadin malabsorption, may be asymptomatic until a viral illness initiates the disease mechanism. Celiac disease is often undiagnosed, and uncovered after the patient is evaluated for other health problems and disease. Patients with constipation, joint pain, fatigue, osteoporosis (due to poor mineral absorption), spontaneous abortion, etc. may suffer from undiagnosed celiac disease. Patients with diverse medical problems, such as autoimmune disorders, neuropathies, blood clotting in the veins (venous thrombosis), etc. have been cured by removing gluten from the diet, suggesting that an undiagnosed Celiac disease is important to the pathology in these cases. Behavioral changes such as depression and schizophrenia may also be caused by celiac disease, and there are theoretical links between autism and celiac disease. Studies have shown that pregnant women with undiagnosed Celiac disease and deficient dipeptidyl peptidase 4 (DDP-4) during pregnancy increase the risks of their child developing schizophrenia dramatically. Studies show that globally 1 in 266 show the genetic makeup of the HLA DQ2 or DQ8 genes (human leukocyte antigens, or HLA), which are linked to Celiac disease, making this potentially the most prevalent genetic disease of human kind, if this genetic trait does signify difficulty with the gluten protein digestion or T-cell response to these proteins. More recent population studies in Europe demonstrate with antibody tests that perhaps an average of 1% of the human population in Europe and the United States has Celiac disease, although this percentage is much higher or lower in specific populations.

Early symptoms of celiac disease, or gluten malabsorption, show only as increased fat in the stools, with a soapy appearance. In severe cases there may be malabsorption of proteins, carbohydrates, calcium, Vitamin K, B12, folic acid and many other important nutrients. These more severe absorption problems produce anemia, wasting, demineralization of the bones, bleeding disorders, and GI problems ranging from H. Pylori overgrowth to constipation and diarrhea. Once again, the symptom presentation in Celiac disease may be difficult to analyze, even for a Medical Doctor. The fact that Celiac disease is most often diagnosed when an associated health problem is being diagnosed shows patients that there is a difficulty in diagnosing Celiac disease, and perhaps even a reluctance.

Patients with celiac disease may also develop malabsorption of lactose and fructose. This may not cause symptoms if only a small amount of dairy or commercial sweetener is consumed, but will cause malabsorption symptoms when sufficient lactose or fructose is consumed. Since fructose is now in most commercial products, this may be a problem with the patient that eats too much processed foods or sweets. Patients with flaring of symptoms when eating sweets and dairy products may have a milder form of Celiac disease.

The autoimmune type of gluten intolerance or celiac disease may be related to changes in commercial flour content of gluten in the early 1970's. At this time, high gluten flour was introduced, speeding production time and reducing costs of production. It is hypothesized that the human body often reacted to this much higher gluten and gliadin content with an allergic reaction that became an autoimmune reaction. The body created excess IgA and IgG antibodies to tissue transglutaminase because high concentrations of this enzyme were produced to speed breakdown of the high gluten levels. Modern research has shown that other diseases, such as dermatitis herpetiformis, is also related to tissue transglutaminase that circulated into the skin dermis. This could explain a wide variety of tissue autoimmune reactions (Journal of Dermatological Science, Vol.34;2;83-90; S. Karpati). Research has also linked antibodies that are specific to gliadin peptides and related peptidases to autoantibody production and dysfunctional membrane peptidases that could cause neuroimmune dysregulation and autoimmunity, in autism for example (Clinical and Diagnostic Laboratory Immunology, May 2004;Vol11;3;5145-524; A. Vojdani et al). Gluten is the alcohol-soluble protein in the grains wheat, barley and rye, and commercial production of high gluten flour incorporates accelerated fermentation of this protein that may alter gliadin peptides. While some genetic and epigenetic factors are associated with the disease, it is now clear that this does not explain all expression of the immune reactions to gluten, and environmental factors are important. Only 4% of the individuals expressing the associated gene DQ2/8 develop Celiac disease. Introduction of high gluten content flours to breast feeding mothers is one area of exploration that is being researched, triggering an epigenetic response in the infant that later materializes as Celiac disease.

Is Celiac disease an inherited or acquired health problem?

Immunogenetics have found that there is no easy explanation to Celiac disease from genetic research. By 2010, it was found that 5 key factors seem to be involved. These include genetic predisposition in the human leukocyte antigen (HLA) major histocompatibility complex (MHC), but also excess stimulation the enzyme transglutaminase 2, which modifies gluten/gliadin peptides and makes them more likely to bind with the HLA complexes, the level and type of gluten intake, the degree of genetic expression of HLA DQ2 and DQ8, and other epigenetic factors that may influence T-cell reactivity (Leiden University Medical Center, Netherlands, Dept. of Immunohematology). Experts agree that there is still no clear way of confirming the genetic inheritance in Celiac disease, and genetics may only be part of the problem even in patients inheriting a propensity for gluten reactivity and malabsorption. Epigenetic inheritance may also play a big part in the disease, and this makes the complexity of the genetic responses elaborate. In short, exploring pharmacological means of engineering biotech drugs to protect against or treat Celiac disease is unlikely. Utilizing a more holistic approach to maintain the health of intestinal mucosa, correct microbial imabalances that contribute to ill health of the intestinal mucosa, stimulate improved immune balance and function, and inhibit the key inflammatory cytokines that perpetuate the antibody responses, while avoiding gluten, or at least, commercial high gluten content flours, seems to be a more sensible approach. While a percentage of patients respond well to simply eliminating gluten from the diet for a period of time, a significant percentage of patients diagnosed with Celiac disease are not cured by this method alone.

Celiac disease is seen in Western civilization with an incidence of 1% of the population, as determined by blood test diagnosis. Many of these cases are still asymptomatic when diagnosed, and are often detected when investigating an associated disease or health problem. Most of the serious consequences of the disease occur with associated disorders, and treatment of celiac disease needs to include therapeutic protocol that addresses these associated health problems as well as the immune reactions in the intestinal lining. Mere treatment of gluten intolerance will not be enough to adequately address the disease and its associations. Each individual must be treated according to their unique health problems, and the therapy should be thorough and holistic. Avoidance of gluten for 6 months often shows clearing of both celiac disease and associated diseases and health problems to some extent, but recurrence of symptoms and chronicity is the norm. Increasingly, autoimmune celiac disease is associated with liver disease, either an autoimmune liver inflammatory disease (hepatitis C) or poor liver function (high liver enzymes may be seen in blood tests). Often the elevated liver transanimases (enzymes) are seen in transient episodes, and so one blood test may be normal, but the next elevated. Primary biliary cirrhosis (bile duct scarring) and primary sclerosing cholangitis (bile duct inflammation) are associated with celiac disease. A variety of autoimmune diseases may be associated, and Type 1 Diabetes and Hashimoto's autoimmune thyroid disorder are seen most frequently of these diseases, but a strong association with psoriasis is also being investigated, with numerous studies showing a much higher incidence of celiac disease among patients with psoriasis than the broad population. An association with cancer is seen, with risk of developing a lymphoma increased five fold. These associated disorders are seen in a percentage of patients over time, as well as a number of other health problems that may not be directly associated. Long-term research is still putting together accurate figures that are reliable as to incidence, but a larger demographic study or studies are still needed.

Differentiating other malabsorption syndromes from true Celiac sprue

Other malabsorption syndromes affect digestion & utilization of Vitamin B12, folic acid, iron, protein, carbohydrates (as in lactose intolerance) & Vitamins A, D, E & K.  These too may be linked to genetic predisposition, autoimmune disorder or imbalance of flora and fauna in the small intestine. They may also be caused by medication side effects. Metformin, a cholesterol lowering drug, and Prilosec & Nexium, drugs that inhibit acid production in the stomach, have been linked to malabsorption of the Vitamin B12 chemicals. Once again, causes of these syndromes may be too complex and diverse for us to ever fully understand, at least until we adopt a more holistic view of medical causes and quit trying to find a single cause for each medical problem. Obviously, a variety of health problems may be causing malabsorption and the related symptoms and diseases, and jumping to the easy conclusion that they may be caused by gluten or lactose intolerance may not solve your health problems. Often, more than on type of malabsorption syndrome may be occurring, and a systematic approach to diagnosis and treatment, and a restoration of gastrointestinal and immune health is a smart approach.

The most common problems in the general population, besides celiac disease, is the malabsorption of lactose (dairy), Vitamin B12 and folic acid, and certain other simple carbohydrates (monosaccharides such as simple sugar & fructose). Lactose intolerance may occur with celiac disease and resolve when gluten is removed from the diet. The symptoms are often mild and varied, making the recognition of these syndromes difficult. Many patients think that they may have a malabsorption syndrome when they do not, while others have a variety of symptoms that no one links to their malabsorption. Adding to this complication is the fact that like gluten, an individual may confuse allergice reactions with malabsorption syndromes. If you experience symptoms after eating less than 8 ounces of milk, or only occasionally after eating more than 8 ounces of milk, you probably aren’t lactose intolerant. You may test yourself by drinking 2 glasses of milk on an empty stomach and watching for symptoms over the next several hours. The following day, eat 2 ounces of hard cheese or drink 2 cups of lactose-free milk and see if symptoms develop. If symptoms develop only on the first day, you may have lactose intolerance. If symptoms develop on both days, you may have an allergy to dairy. Typical symptoms of lactose intolerance are increased gas, or flatus, foul smell, loose stools, and increased bowel motility and irritation after consuming enough lactose. A careful analysis will end the uncertainty. Many chemicals in cow's milk may cause an allergic reaction, not only the milk proteins, but also chemicals used to raise and treat the cow. The two most common protein allergies are to casein and whey. Casein accounts for 80 percent of the protein in milk, and is the curd that forms when milk is left to sour, from which cheese is made from. Whey is the watery part of the milk left when the casein-rich curd is removed. Most individuals with dairy allergy are allergic to the casein, and consumption of whey protein supplements will not cause a reaction.

Symptoms of milk allergies are varied and studies have shown that they may change over time. One study of children with dairy allergies found that at the beginning of the study, most of the children had primarily gastroentestinal symptoms, such as indigestion and diarrhea, but by the end of the study, many had switched to respiratory symptoms, such as asthmatic wheezing, sneezing, and runny nose. Milk protein allergies are divided into 3 categories, skin, gastrointestinal, and respiratory. Gastrointestinal symptoms may include abdominal bloat, diarrhea, nausea, gas, and cramping. Respiratory symptoms may include runny nose, sneezing, watery or itchy eyes, cough, wheezing, or shortness of breath. Skin reactions may include itchy red rash, hives, eczema, swelling of the tongue, mouth, throat, lips or face, and even blackened skin around the eyes. If milk allergies are suspect, alternatives to cow's milk include goat's milk, which the individual may also be allergic to, soy milk, which most people with milk allergies are also allergic to, and are often hard to digest, and rice milk, which may be the preferred alternative.

Symptoms of lactose intolerance are usually excess gas production, stomach ache & diarrhea after eating dairy, although most lactose intolerant persons may eat up to 8 ounces of milk per day without experiencing severe symptoms, and hard cheese will often not affect them. Excess gas is produced by a growing group of bacteria that feed on the undigested lactose (lactobacilli), while diarrhea is caused by the fast emptying of excess undigested lactose from the intestine. Throughout history, it is believed that most humans quit producing the enzyme needed for lactose digestion between the ages of 2 and 5, yet many Europeans & Middle East peoples seem to have developed a genetic trait to continue producing significant amounts throughout adulthood. Populations that chose to avoid dairy in adult diet, like the Central Asian & African populations, often have difficulty digesting lactose. Studies have shown that up to 80% of African Americans, rural Mexicans & South Americans, Lebanese, & North American Jews, and almost 100% of Native Americans, Southeast Asians and Chinese are lactose intolerant, although with the changes in diet in these populations, the ability to develop production of enzymes that aid in lactose digestion may be increasing.

What complicates this scenario is the fact that many babies now have difficulty with cow’s milk yet no difficulty with human or goat milk. Obviously, something in the cow’s milk is causing an allergic type malabsorption, and science has still not fully explained this phenomenon. Since most commercial cow's milk in the United States is obtained from cows that are not grazed, and fed many chemicals and antibiotics, some experts surmise that this may be the explanation. Over 25 different molecules in cow's milk have the potential to elicit an allergic reaction, making analysis of this problem difficult. Medical doctors now caution all mothers to avoid cow's milk, but only a small percentage of children in some populations will have this reaction. Studies have shown that only about 2-3 percent of infants shown an allergic reaction to cow's milk, and a significant percentage of these infants will also show an allergic reactivity to soy protein as well. Adults too seem to develop a difficulty with cow’s milk at times, while tolerance for goat milk is normal. Most goats are still grass fed and require little or no chemicals and antibiotics to keep healthy. Besides an allergic reaction, lactose intolerance is also seen in infants, and often confused with allergic reaction. Since lactose is found in mother's milk and goat's milk, inherited lactose intolerance would also produce symptoms with these foods as well.

Fructose intolerance produces excess gas and constipation, or diarrhea with bloat and stomach pain from spasm. This condition is common in patients with irritable bowel syndrome (IBS). Celiac disease may also produce fructose intolerance. A more rare syndrome is fructose intolerance, where specific liver enzymes are not produced to digest the fructose, resulting in hypoglycemia and nausea, but not the malabsorption symptoms. Since fructose, and high fructose corn syrup, are now the most common types of sweeteners, Celiac disease may be indirectly linked to liver dysfunction and Metabolic Syndrome, or type 2 diabetes.

Diagnostic tests for malabsorption syndromes:

Often, when malabsorption syndromes are suspected as a cause of disease or symptoms, tests will be performed. When one or two tests, such as a blood test for anti-gliadin antibodies, is performed and comes back with a negative indication on the blood test, this does not mean that the patient is not experiencing a malabsorption syndrome or Celiac disease, it is only one piece of information in a puzzling health problem. If the disease or symptoms persist, the patient needs to be persistent that more tests are conducted to clarify the diagnosis, especially is no other disease or health problem is found to explain the pathology.

• C-xylose breath test: the amount of exhaled CO2 in response to C-xylose suggests the degree of bacterial overgrowth flora.
• Hydrogen breath test: takes 2-3 hours & measures the degree of nonabsorbed carbohydrates passing to the colon and degraded the bacteria there, with increased hydrogen rising through the intestines; confirms lactose intolerance when 50 grams of lactose are taken on an empty stomach prior to the test; also used for fructose intolerance.
• Lactose-H2 breath test:  another name for the hydrogen breath test; confirms lactase deficiency.
• measuring the blood glucose every 10-15 minutes after ingestion of lactose
• Schilling test: a 4 stage test to confirm B12 malabsorption and determine whether the cause is related to pernicious anemia, pancreatic exocrine deficiency, bacterial overgrowth, or ileal disease. Radiolabeled cyanocobalamin is given orally and a 24 hour urine collection is measured to determine cobalamin malabsorption; repeated for intrinsic factor (a molecule secreted in the stomach to absorb B12); repeated with pancreatic enzymes; repeated after giving the patient antimicrobial therapy (antibiotics). The test results give clear information but still the condition may be somewhat confusing as to the cause of the problems.
• Endoscopy with biopsy of the small bowel: the mucosa is examined for atrophied villi, increased blood cells in the bowel lining, and enlarged or swollen crypts. These findings can suggest celiac sprue, tropical sprue, severe intestinal bacterial overgrowth, eosinophilic enteritis, lactose intolerance or lymphoma. Other tests must be given to determine the actual diagnosis.
• Blood tests: markers in the blood, antibodies to pathogens, such as AGA & EMA, can help with the diagnosis. Often though, celiac disease patients are deficient in IgA, decreasing sensitivity. Total IgA should be analyzed. Also, AGA-G or antigliadin IgA antibody may be positive in persons who don’t have celiac disease. IgA anti-tissue transglutaminase should also be tested, as this is pretty specific. IgA endomysial autoantibody (EMA) levels are also useful, and have both a high sensitivity and specificity. These tests are useful to determine whether the gold standard of testing for celiac disease, the endoscopy with biopsy, is warranted.
• Stool samples: tested for undigested fats, or steatorrhea, may help the diagnosis. Sampling of stool samples for acidity may also be of value.
• Celiac disease has been discovered upon positive screening of a number of other blood markers, including anti-tissue transglutaminase autoantibodies, TPO (thyroid peroxidase antibody), and other markers, and data is still being collected to determine accuracy of association.

Often, the patient decides that it is easier and quicker to just systematically eliminate foods from the diet that may be causing the problem and see what happens, rather than wait and go through the testing process, which sometimes is difficult to obtain insurance reimbursement for. If this path is chosen, it is important that one be objective, keep a diary of results, and not jump to conclusions. An objective mind with medical knowledge is usually needed, and the knowledgeable Licensed Acupuncturist or Naturopathic physician can help you make objective sense of your condition while also helping to improve your health and make positive changes to your diet. Unnecessary elimination of nutrients can also have negative long-term affects and you should be careful of your choices. Our health depends on good nutrition, and when you think that there is a health problem you should try hard to improve your diet. Don’t let habits and food preferences ruin your health. Your preferences will change once you get used to a different diet.

The Pathophysiology of Celiac Disease

Celiac disease presents a complex and confusing array of events to researchers. As research progresses, we are finding that, like many chronic inflammatory autoimmune diseases, a sequence of events of immune dysregulation are occurring that involves both the innate and adaptive immune complement system. Finding one specific inflammatory dyfunction with which to base an allopathic pharmacologic response is not practical in designing an effective treatment protocol. Gluten is a type of protein found in various grains (especially wheat, barley and rye), and gliadin are protein fragments, or peptides, found within gluten. Altered gliadin peptides are thought to trigger a cascade of immune reactions. The membrane of the intestine contains an elaborate system of protecting us from potentially harmful toxins and antigens. Celiac disease describes the dysfunction of this protective gut membrane in relation to immune response. Both a mechanical and chemical protection has evolved. Intestinal permeability appears to play a large role in the ability of the gliadin proteins to penetrate near the blood circulation and initiate chemical responses. Altered gliadin peptides, or peptide derivatives (33-mer and p31-34) have been found to induce a chemical called zonulin that increases intestinal permeability, macrophage expression, and cytokine release. This initial innate immune response then may trigger macrophages in the intestinal lining to stimulate adaptive immune responses within the intestinal mucosa. The resulting immune dysregulation involves a number of proinflammatory cytokines that ultimately lead to an adaptive antibody response that can become poorly controlled.

Intestinal permeability, or loss of intestinal mucosal barrier function, is one key apsect of the pathophysiology of Celiac Disease that needs to be addressed in therapy. Called ‘Leaky Gut Syndrome’ by many researchers, this problem occurs as a result of gradual gastrointestinal dysfunction. Normally, the lining of the intestines allows only molecules that are broken down in digestion sufficiently through to the enteric blood system. A system of mucosal barriers protects us from larger food molecules as well as toxins, antigens and harmful microbes. This includes both mechanical and chemical barriers with an elaborate immune complement response. With mucosal irritation, this barrier breaks down, but a number of other factors may also come into play. The balance of flora and fauna in the gut, or microbial balance, is very important to our health, acting in a symbiotic way to both protect us from microbial overgrowths, but also to provide our bodies with key nutrients produced by these symbiotic microbes. When microbial imbalances occur, penetration of the intestinal mucosa by various microbes, such as the fungal form of candida species, becomes easier, contributing to breakdown of the intestinal permeability. The resulting increased immune response contributes to a host of diseases. Leaky Gut Syndrome is associated with Celiac disease, Irritable Bowel Syndrome, Allergic and Environmental hypersensitivities, Asthma, Psoriasis, Eczema, Arthritis, Chronic Fatique Syndrome, Liver dysfunction, and more. Individualized assessment and therapy with a a step-by-step approach is often needed to restore a healthy intestinal mucosa. Refer to the article on this website entitled Irritable Bowel Syndrome to learn more about functional GI disorders and the role of acupuncture, herbal and nutrient medicine in correcting this multifactorial problem with an individualized approach.

Gluten and gliadin protein fragments, or peptides, are triggers of the membrane immune responses in most cases of Celiac disease. Our bodies normally clear these protein fragments from the tissue by breaking them down, or catabolizing them, and the rate of this catabolism is regulated by the amount of enzyme activity associated with depeptidyl peptidase 4 (DDP-4). Research has uncovered a consistent deficiency of DDP-4 activity in the small intestine membranes of patients with Celiac disease. The underlying causes of DDP-4 deficiency are complicated, though, by the fact that this enzyme participates in an elaborate feedback digestive mechanism that tries to normalize a number of aspects of our digestion. DDP-4 not only increases the breakdown of peptides, but also inactivates hormones called incretins (GLP-1 and 2) that are released by cells in the stomach and small intestine that regulate insulin release after eating as well as the rate of gastric emptying. By reducing the rate of gastric emptying, the stomach acids are more likely to break down proteins and peptides, and stomach acids are more likely to be neutralized before entering the small intestine. Treatment of gastric hypofunction may be the first step in resolving Celiac disease.

Normally, proteins, which are relatively large molecules, need to be broken down sufficiently before entering the small intestine. The modern diet often contains a high percentage of proteins and simple carbohydrates. Simple carbohydrates quickly raise blood sugars and stimulate an increased immediate insulin response. Protein breakdown creates a large amount of urea, and delayed gastic emptying and slow gastric function, or gastric hypofunction, results in an excess amount of urea accumulating in the stomach. Heliobacter pylori are a type of symbiotic bacteria that imbed into the stomach lining and produce the digestive enzyme called urease. It is postulated that excess of H. pylori, which is diagnosed in many cases of Celiac disease, as well as stomach and intestinal ulcer occurrence, and stomach cancers, is due to the need for increased urease. The partial breakdown of proteins, such as gluten, in the stomach is accomplished by the digestive secretion called pepsin, and slow gastric emptying, and a large pepsin response, may increase the accumulation of urea in the stomach and hence the need for increased urease.

As stated, dipeptidyl peptidase 4 (DDDP-4) is integral to the digestion of gluten gliadin protein fragments, but also to the activation of intestinal hormones called incretins that help regulate insulin release from the pancreas. Medical doctors now prescribe a drug that is an inhbitor or DDP-4, called Januvia, for patients with Metabolic Syndrome that has turned into Diabetes Type 2, with high circulating blood glucose. The inhibition of DDP-4 by this anti-diabetic drug, though, may have implications in the pathology of Celiac disease. Since many patients with Metabolic Syndrome may also have symptoms explained by Celiac disease and sprue, this should be discussed with the prescribing physician.

While these processes may seem complicated, they do explain the various problems commonly associated with clinically symptomatic Celiac disease. They also show us that restoration of normal feedback mechanisms, or homeostasis, in gastrointestinal function, are important to clear Celiac disease. Enzymes produced by cells in the small intestinal membranes help break down gluten and gliadin peptides that accumulate and stimulate antibody immune responses. These enzymes also affect hormonal regulation of pancreatic secretions and excretions (digestive enzymes and insulin) and acidity in the small intestine by affecting the rate of gastric emptying. Increased acidity allows for an environment that increases microbial imbalance and results in such problems as candidiasis, as yeasts such as candida overgrow in acidic environments and turn into fungi. There is still a lack of research that looks at these problems from a holistic perspective. Research is funded mainly by the pharmaceutical industries and the researchers are looking at isolated parts of this feedback mechanism to create new pharmacological drugs. Hence, there is still a lack of analysis of the big picture. What we get are drugs that inhibit pepsin production to counter acid reflux, and drugs that inhibit DDP-4 to treat diabetes by indirectly increasing incretin to indirectly inhibit glucagon, thereby theoretically stimulating increased insulin release. Side effects of these drugs apparently increase the conditions that underly Celiac disease. Holistic medicine, on the other hand, looks for treatment protocols that restore normal gastric function, normalize the acidity and feedback mechanisms of gastrointestinal function, and restore immune function. Research into this realm of medicine is still underfunded, and researchers are not trained to adopt a holistic perspective in their research, but progress is being made as more government funded, or public, research is created.

Considerations of treatment strategies in Celiac diseas and malabsorption syndromes

While standard medicine is finally acknowledging the role of intestinal permeability and functional GI disorders in Celiac disease, the suggested therapies are a matter of debate. A theory of small intestine bacterial overgrowth has been used to increase the prescription of antibiotics, but is this the proper and effective therapy? Bacterial overgrowth is due to a variety of factors that lead to an imbalance of the normal symbiotic microbial colonization. Restoration of the balance of symbiotic microbial colonization in the small intestine is necessary to achieve a lasting healthy effect. Destruction of bacterial colony with antibiotics does not really achieve this goal, and in fact is well known to lead to further imbalance. Side effects of antibiotics include increased urinary tract infections and candidal overgrowths due to the destruction of normal bacterial balance that is absolutely necessary to prevent unhealthy overgrowths of some of the more than 1200 microbial species that inhabit our gut. Use of digestive enzymes and probiotics are just two of the useful tools needed to restore health. Professional guidance can be very important with this therapeutic restoration, as acidic imbalances, autonomic dysfunction, hormonal imbalances, and other factors may play a part in the pathology. Simply taking a probiotic does not guarantee the colonization with those probiotic bacteria.

How do these gluten and gliadin peptides accumulate in the small intestine lining, or membrane, is a key question in the understanding of the pathophysiology of Celiac disease. Normally, proteins are broken down in the stomach during digestion by enzymes known as proteases, or proteolytic enzymes, and the key enzyme in protein catabolism is called pepsin, which breaks down large proteins into smaller peptides. The pepsin comes from a precursor chemical called pepsinogen, which is converted to pepsin as needed when the stomach acid is increased with release of hydrochloric acid. Pepsin breaks down a certain percentage of protein bonds, and certain types, but does not complete the breakdown of proteins. Not all nutrient proteins are alike, and so some proteins, such as gluten and gliadin, may be more difficult to fully break down. As these partially broken down proteins, polypeptides, exit the stomach, the pancreas secretes other proteolytic enzymes, or digestive enzymes, to continue the process of breaking down these gluten and gliadin peptides. With stomach hypofunction, acid production is slow, and pepsin does not break down the gluten and gliadin proteins efficiently.

Pancreatic proteolytic enzymes are stimulated by chemicals secreted from the cells of the small intestinal lining. As the small intestinal lining becomes less healthy, this process in inhibited. Slowed digestion creates bloat and discomfort, malabsorption occurs, acidic control is decreased and the balance of symbiotic microbial colonies are upset, and intestinal permeability is increased. The hard to break down gliadin peptides accumulate in the small intestinal membranes, and immune responses to clear this irritation create inflammatory responses and eventually autoimmune responses. This also allows for less immune efficiency to clear viruses in the digestive circulation, and hence, this circulation, which first goes to the liver, results in hepatitis C. An array of other associated diseases, such as chronic fatique syndrome, may also be related to viruses such as Epstein-Barr, coxsackie, cytomegalovirus, parvovirus, and HTLV. Full restoration of the gastrointestinal function and tissue, as well as immune restoration, would address these associated disorders in advanced Celiac disease as well as the responses to gluten and gliadin peptides. This is best accomplished in a step-by-step process, and professional guidance with a knowledgeable Complementary Medicine physician is very important.

One part of gluten and gliadin protein that is found to be particularly hard to break down is proline, which constitutes about 12-17% of the gluten, and is a peptide that is difficult to break down in the stomach. Normal proteolytic enzymes do not efficiently break down proline peptides, and it is postulated from research that these peptides may be related to many of the immune responses in the small intestinal membranes. Research since the 1950s has sought a nonhuman proteolytic enzyme to break down prolines in the stomach, but the enzymes discovered did not survive well in the gastric environment. Currently, another proteolytic enzyme that successfully breaks down proline peptides is being developed as a nutritional medicine. A prolyl endopeptidase derived from Aspergillus niger fungus, is undergoing current human clinical trials in the Netherlands, and may be available to add to the treatment regimen. Various enzymes from the Aspergillus niger are currently being utilized in the production of high fructose corn syrup and wine clarification, as well as in the product called Beano, which utilizes alpha-galactosidase from Aspergillus niger to decrase flatus. The enzyme prolyl endopeptidase (AN-PEP) may be a safe and inexpensive addition to the Complementary Medicine treatment protocol for Celiac disease. Such research is not only providing more tools for the Licensed Acupuncturist in treatment, but is explaining the underlying reasons for Celiac disease more clearly.

Recent research has uncovered key cytokines that perpetuate Celiac disease, and these are important to address in the treatment protocol as well as the more efficient breakdown of gluten and gliadin peptides, especially if the Celiac disease has progressed to a more complicated stage. IL-8 (interleukin-8) and IL-15 are two of these key inflammatory modulators that may be overexpressed or not kept in check with other inflammatory cytokines. IL-8 is an inflammatory cytokine that is found to be induced by gliadin peptides and may be stimulating many of the symptoms. IL-15 cytokine antibodies have been found to neutralize many of the innate immune responses noted in Celiac disease, implicating this cytokine in the autoimmune response. IL-15 suppresses natural cell-death cycle (apoptosis) of T-cells in humans with Celiac disease, inhibiting the normal modulation of immune responses. The IL-15 receptor also acts as a hormonal receptor for hematopoetin, which stimulates creation of new red blood cells, linking excess IL-15 to deficient hematopoesis, and the anemias often seen in Celiac disease. IL-15 is normally secreted by immune cells following viral infection, inducing greater production of natural killer cells (NK), but viruses may not be the only thing that stimulates IL-15 secretion. IL-15 has also been shown to secrete chemical signals that perpetuate certain T-cell responses in the abscence of antigens. IL-8 is a cytokine that is prolific on membrane epithelia, and acts as a chemokine produced by macrophages and other cells in membrane epithelia. Once the Celiac disease is initiated, IL-8 may be overexpressed due to the excessive colony of macrophages maintained in the intestinal membrane. The primary function of IL-8 is to induce chemotaxis, signalling other cytokines to attract to the tissues. IL-8 is associated with a host of chronic inflammatory diseases, such as bronchitis, psoriasis, gingivitis, and may be a link between Celiac disease and associated diseases and health problems.

Recent research and treatment options for malabsorption syndromes

Decrease in activity of a key enzyme in the small intestine has been found in most cases of gluten gliadin intolerance and celiac disease. The lack of enzyme activity of dipeptidyl peptidase IV (DPP-IV) leads to the accumulation of gluten gliadin and other protein fragments in the intestinal lining, resulting in the immune responses and an inflamed intestinal linings of the small intestine that are the hallmark of malabsorption syndromes and Celiac disease. Use of specific therapeutic enzymes may restore this enzyme activity and reverse the ill health of the intestinal lining. A comprehensive therapeutic program may take a step-by-step approach to restoration of intestinal health to correct this syndrome, and may result in not only improved digestion, but a healthier immune system, and decrease in such problems as allergies, autoimmune disorders and hormonal imbalances linked to increased immune stress. In addition, resolution of malabsorption may have positive effect for such problems as anemia, osteoporosis, and functional GI disorders, such as irritable bowel syndrome and reflux disease. With improved health of the GI lining, overgrowth of heliobacter pylori, candida, and other flora and fauna imbalances may resolve. A patented blend of enzymes that increases the activity of dipeptidyl peptidase IV is part of a comprehensive treatment protocol that may resolve Celiac disease and restore GI function.

A comprehensive approach to the treatment of Celiac disease, malabsorption syndromes, and functional GI diseases may combine acupuncture with herbal and nutrient medicine to restore the health of the stomach and intestines, correct immune and autonomic dysfunction, and treat associated diseases and health problems. Other aids in the therapy could include N-acetyl cysteine, serratiopeptidase, bovine colostrum, and 5HTP. If GERD is also a problem, a systematic restoration of normal stomach function could be added to the therapy, and if irritable bowel syndrome is present, here too, specific therapeutic protocol to normalize function of the intestinal tract and decrease anxiety and stress could be included in the treatment protocol. By adhering to such a course, even difficult GI health problems can be overcome along with malabsorption syndromes. The total benefit to the health could be dramatic.

A number of Chinese herbs are proven to significantly inhibit IL-8 and other pro-inflammatory cytokines that are integral to the autoimmune dysfunctions in Celiac disease, and formulas with these herbs may be used in short courses to decrease the pathology of Celiac disease expression and promote healthier digestion at the same time. A number of viral and microbial infections may be also associated with the pathology of Celiac disease, and Chinese herbal formulas may include a wide variety of herbal chemicals that clear these infections as well. While allopathic pharmacological therapy utilizes single chemicals, herbal medicine incorporates a host of chemicals that have evolved in medicinal plants to achieve a number of related goals. Following these with a professional Probiotic formula of assured quality will help to eventually restore healthy GI microbial balance. As research progresses, much is being learned about new probiotic species and the nutrient chemicals that increase the colonization when they are taken. A new probiotic approved by the FDA is called Culturelle, and is shown to increase the ability of the intestine to colonize healthy new probiotic bacteria. As research progresses, a number of specific treatment protocols are being verified and discovered that allows your Complementary and Integrative physician to better insure a successful outcome.

Information Resources

1. In 2010, a large population study in 4 countries in Europe found a prevalence of Celiac disease averaging 1%, with 68% of antibody-positive individuals also showing small intestine mucosal changes associated with Celiac disease: http://www.ncbi.nlm.nih.gov/pubmed/21070098
2. Celiac disease is sometimes associated with liver dysfunction or autoimmune hepatitis: http://www.ncbi.nlm.nih.gov/pubmed/18496773
3. A review of health problems and diseases associated with celiac disease is reviewed in 2010 by the University of Nottingham, UK: http://www.ncbi.nlm.nih.gov/pubmed/21108596
4. Celiac disease is often detected in the abscence of direct symptoms of the disease, and a diverse array of associated health problems investigated by doctors often leads to a positive test for celiac disease, including anemia, autoimmune disorders, and inflammatory bowel disease, according to a 2007 review at Singleton Hospital in Swansea, UK: http://www.ncbi.nlm.nih.gov/pubmed/18056028
5. In 2007, experts at the University La Sapienza, in Rome, Italy, noted that the association of celiac disease with autoimmune thryoiditis is frequently noted, and suggests that guidelines be established to that all subjects testing positive for TPO (thyroid peroxidase antibodies) should be screened and tested for celiac disease: http://www.ncbi.nlm.nih.gov/pubmed/18091661
6. In 2010, research at Johns Hopkins University School of Medicine found a type of gliadin protein found in gluten that induced a specific IL-8 (interleukin 8 cytokine) immune response. Such research offers suggestions to guide therapy in Complementary Medicine more specifically: http://www.ncbi.nlm.nih.gov/pubmed/21091908
7. Baicalein, a chemical found in the Chinese herb Hurang qin, or Scutellaria baicalensis, was found to significantly inhibit IL-8, and other inflammatory cytokines that may be associated with celiac disease pathogenesis, in a dose-dependant manner, according to research at East Tennessee State University: http://www.ncbi.nlm.nih.gov/pubmed/18039391
8. In 2010, research at the University of Dongguk, in South Korea, found that the Chinese herb Dragon's Blood, or Dracona Resina, inhibited IL-8, along with other inflammatory cytokines that may be integral to the pathology in celiac disease: http://www.ncbi.nlm.nih.gov/pubmed/19577610
9. In 2010, research at Fudan University in Shanghai, in animal studies investigating treatment of pancreatic cancer, found that a Chinese herbal formula, Qingyi Huaji (clear the pancreas and small intestine, transform accumulation), significantly lowered serum levels of IL-8 and other inflammatory cytokines associated with Celiac disease pathogenesis (Baihuasheshecao/Hedyotidis, Banzhilian/Scutellaria, Moyu/Amorphophalli, Jiaogulan/Gymnostemmatis, Baidoukou/Amomi): http://www.ncbi.nlm.nih.gov/pubmed/20619142
10. In 2005, researchers in Italy found that immune responses to altered gliadin peptides in celiac disease were complex, initiating immune dysregulation in both innate and adaptive immune responses (T cell and B cell), and that most of the innate immune responses appear to be inhibited by antibodies neutralizing IL-15 (interleukin-15): http://www.ncbi.nlm.nih.gov/pubmed/19577610

The information on this website is not intended to be used as a specific medical advice or cure. Please consult with the practitioner or an appropriate physician, such as a licensed acupuncturist, naturopath, or medical doctor, to discuss the proper application of the information contained on this website.