Encephalomyelitis, Myalgic

"My stomach is really bothering me. What can I do about it?" "She's been so depressed and tired lately." "I've never had any problems with allergies before, why now?" Doctors would usually regard and treat these conditions separately with Tagamet for stomach problems, Prozac for depression, or allergy medication for allergies. But might these complaints, heard everyday in doctor's offices nationwide, be related?

Perhaps one overlooked association with these seemingly unrelated complaints is food related intolerances. Doctors just aren't aware of the role food antigens play in contributing to a disease state, with the exception of allergies. In fact, researchers are finding that health conditions related to the ingestion of "gluten," a protein most often found in wheat, rye, barley and oats, are becoming epidemic.

Celiac Disease (CD), an autoimmune disease that is considered the most common of the gluten disorders, is often overlooked as a diagnosis. CD patients often suffer from symptoms such as stomach complaints, depression and allergies. Many other autoimmune diseases are also associated with gluten intolerance including Type 1 Diabetes, Autoimmune Thyroid Disease, Rheumatoid Arthritis, as well as others.

Gluten intolerance is now being associated with Autistic Spectrum Disorders and Attention Deficit Disorders. The type of gluten intolerance associated with these conditions is considered to originate from the body's inability to break down the gluten and casein proteins rather than an autoimmune response, as in CD.

Researchers are also beginning to see a connection between gluten and other disorders, which seem to share characteristics such as biochemical, neurological, and immunological abnormalities. These "Overlapping Syndromes" are conditions such as Gulf War Syndrome, Chronic Fatigue Syndrome, and Fibromyalgia Syndrome, as well as others. Also, some psychological disorders such as depression and panic disorder as well as skin conditions such as psoriasis are suspected to have a gluten-related component.

Wheat

According to Dr. Loren Cordain, a renowned expert in Paleolithic nutrition, Paleolithic humans ate mostly fruits, vegetables and lean game meats. (1) The agriculture of cereal grains began in the Near East about 10,000 years ago and then spread to northern Europe about 5,000 years ago. "Because the estimated amount of genetic change which has occurred in the human genome over this time period is negligible, the genetic makeup of modern man has remained essentially unchanged from that of pre-agricultural man. Consequently, the human genome is most ideally adapted to those foods which were available to pre-agricultural man, namely lean muscle meats, limited fatty organ meats, and wild fruits and vegetables." (2)

In fact, the amount of cereal grains being consumed has increased tremendously in the last 200 years with the industrial revolution and more recently, with the technology revolution. With even more growth in the last 50 years, these changes have spurned more packaged and processed foods. We have also managed to greatly enhance the gluten content through genetic selection of wheat. "Today 50% of the protein in wheat is gluten, a characteristic that facilitates bread baking and adapts the grain well to cultivation and harvesting." (3)

Problems with the ingestion of gluten were first noted in the 2nd Century AD. Aretaeus the Cappadocian described the condition, "coeliac disease," as a chronic diarrhea condition consisting of undigested food, lasting an extended period, and a debilitation of the whole body. (4) Samuel Gee, in 1887, noted the disease affected persons of all ages and recognized that a gluten-free diet was the main treatment.

Gluten Intolerance Connection

Celiac Disease is considered a malabsorptive digestive disease, which is autoimmune in nature. Upon consumption of gluten-containing foods, the immune system responds by producing antibodies, which damage the small intestinal villi and lead to villous atrophy. Symptoms of CD arise from the damage done by the immune system, to the small intestine.

Symptoms of CD vary from person to person which makes it very difficult to diagnose. Symptoms may include recurring abdominal pain, chronic diarrhea/constipation, weight loss, anemia, fatigue, delayed growth, joint pain, seizures, tingling/numbness in the legs. Others might suffer from psychological disturbances like irritability or depression; 50-60% of untreated CD patients are asymptomatic! (5)

CD is most commonly misdiagnosed with conditions such as; anemia, irritable bowel syndrome/disease, psychological stress, diarrhea, diabetes, spastic colon, ulcers, viral gastroenteritis, Chronic Fatigue Syndrome, allergies, parasite infection, gall bladder disease, thyroid disease, colitis, and lactose intolerance. Dr. Vijay Kumar, a leading CD researcher, reports that the majority of CD patients had visited 5 or more doctors prior to diagnosis and that it had taken an average of 5 to 10 years, after initial presentation, for CD to be diagnosed.

Part of the problem is that doctors are taught in medical school that one in 5,000 have CD. The reality is more like 1 in 150 and it may be even higher. (6) Arecent report in JAMA, found that the prevalence of CD in 1200 screened children and adolescent patients ranged between 1 in 57 and 1 in 33. (7)

The only treatment available for CD is to remove all forms of gluten from the diet. Glutens are proteins that come from the Plant Kingdom Subclass of monocots and are members of the grass family of wheat, oats, barley, rye and triticale. There are many hidden sources of gluten in our foods. Some of these come in the form of: malt, grain starches, hydrolyzed vegetable/plant proteins, textured vegetable proteins, grain vinegars, soy sauce, brown rice syrup, dextrin, modified food starch, mono and di-glycerides, natural and artificial flavors, grain alcohol, and the binders and fillers sometimes found in vitamins and medications. Also, many people assume that if a product says "wheat free," that it is gluten-free, which is not the case. For example, Kamut and Spelt are wheat free grains but they contain gluten.

Cross contamination is another problem. Sometimes restaurants use the same cooking materials when preparing gluten and non-gluten containing food, which is then mixed into the meal. Or cultivation of the non-gluten containing grains is done in the same fields, factory or equipment as the gluten-containing grains and there is cross-contamination. If these sources are not removed, the intestine cannot heal, and the patient will not know the benefit of a gluten-free diet.

Autism

Research on children with Autistic Spectrum Disorders (ASD), show many suffer from some small intestinal damage, while only a very small percentage test positive for CD. (8) It appears that "some people have intolerance to these proteins but do not seem to mount an immune response of the sort identified in gluten sensitivity by current testing methods." (9) Positive results have been indicated with Autistic children on a very strict, gluten-free (GF), casein-free (dairy), diet. (10) A single-blind, 2-year study found that children with autism improved on a gluten-free, casein-free diet, but regressed if the diet was stopped. (11) Symptom improvements include speech, sociability, behavior and sleeping habits, as well as others. (12)

Gluten intolerance, in Autism, is thought to be related to the incomplete digestion and breakdown of proteins. Normally, proteins are digested by enzymes in the intestines and are broken down into long chain amino acids. With maldigestion, short chains of these amino acids, known as peptides, will develop in excess amounts and enter the bloodstream. Peptides from proteins such as gluten and casein, called "exorphins," are biologically active. They interact with opiate receptors in the brain and have the same effects as opiate drugs like heroin and morphine and are also addictive. There are 15 opioid sequences in one molecule of gluten. (13) In fact, the peptides can be up to 30 times more potent than morphine.

The effects of opioids on the body are numerous. (14) "Opioid peptides are key signaling molecules between the endocrine, immune, brain nerve tissues, and the pineal complex, the latter is particularly associated with circadian rhythms." (15) Any abnormal alteration in the quantity of these peptides will have a detrimental effect on all of these systems. Some of the other effects on the body are decreased gastric acid secretion, reduced glutathione levels, immune system depression and modulation of cholecystokinin levels. All of these effects contribute to the inhibition of normal brain, bodily function and growth.

Attention Deficit Hyperactivity Disorder

A growing body of research is also implicating peptides as a factor in ADHD. (16-18) A study on children diagnosed with ADD showed they had peptide containing complexes in their urine, which seems to be related to hyperactivity. (19) "Hypoarousal, in some regions of the brain, has long been recognized as a feature of ADHD. The possibility that there is a narcotic effect from opioid peptides is very consistent with such reduced arousal, with comorbid learning disabilities, and with the DSM IV observation that ADHD children "often appear as if their mind is elsewhere or as if they are not listening or did not hear what has just been said (Criterion Alc)." (20)

Overlapping Syndromes

Malcolm Hooper from the University of Sunderland has found that Autistic, Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, ADHD and Gulf War Syndrome patients have high levels of a metabolite called Indolylacoylglycine (IAG) in their urine. (21) IAG is derived from abnormal tryptophan metabolism and is a metabolite of indol-3-ylacrylic acid (IacrA). It is indicative of a malfunctioning digestive system, which in turn leads to the development of opioids from gluten and casein.

Gulf War Syndrome (GWS) has also been associated with Chronic Fatigue Syndrome (CFS) and Fibromyalgia Syndrome (FMS) in the sharing of symptoms and biochemical abnormalities. (22) Symptoms often include: fatigue; joint pain, headache, cognition/memory problems; sleep disturbances; depression/anxiety; skin problems; gastrointestinal disturbances; eye problems; allergies/chemical sensitivity; cardiac arrythmias; etc.

They also tend to share biochemical abnormalities such as vitamin/mineral deficiencies, fatty acid imbalances, amino acid imbalance/deficiencies, liver function abnormalities, immune system irregularities, hormonal imbalances, heavy metal toxicity, gastrointestinal dysbiosis and overgrowths of fungus, parasites and bacteria. Research is finally tying these syndromes together and calling them "Overlapping Syndromes." Other conditions considered to be associated with Overlapping Syndromes include Multiple Chemical Sensitivity, Myofascial Pain Syndrome, and Irritable Bowel Syndrome. "It is clear that a number of understood chronic conditions appear to share a common set of biochemical markers.... These shared characteristics are part of common mechanisms of pathology associated with a number of overlapping syndromes." (23)

The Neuro Immune Dysfunction Syndrome (NIDS) Research Institute is studying the association between disorders such as Autism, ADD, Alzheimer's, Amyotrophic Lateral Sclerosis, Chronic Fatigue Syndrome, Multiple Sclerosis and other immune-mediated diseases. They suggest that the connection also includes brain function abnormalities and various immune abnormalities including T-cell changes. (24)

Researchers are finally noting the association with improved health of these patients on a gluten-free (GF) diet. Reichelt and Shattock recommend a GF diet for GWS patients to diminish the effect of opioids on the body. "No formal study has been performed but it is our very clear impression that those individuals who have experimented in this way, entirely at their own expense, have shown impressive improvements in many diverse ways including speech and aggression control and bowel function." (25) Dr. Paul Cheney, a leading CFS researcher, recommends diet modifications, including gluten restriction for CFS and FMS. (26) A recent study by Skowera, et al. found a high prevalence of serum markers of CD in patients with CFS. (27)

Other Gluten-Related Problems

Ron Hoggan, MA has studied gluten intolerance extensively and has written many articles on the topic. He suggests that depression is another result of gluten intolerance. (28) The theory behind this assumption is similar to the "opioid" theory in Autism. The morphine-like exorphins, derived from the incomplete breakdown of grains and dairy, alter mood by depressing seratonin, dopamine and norpinephrine levels. The effect on Seratonin is important in depression. "Seratonin is an important neurotransmitter which is needed for sleep onset, mood regulation, carbohydrate craving and consumption and a host of other functions." He suggests that it would not be surprising if the intestinal permeability and digestive enzyme deficiencies found in CD were also found in people suffering from depression. Panic disorder is also suspected to originate from the same gluten exorphins. (29)

It is well known that the skin disorder Dermatitis Herpetiformis is related to CD. A study on Psoriasis patients also revealed that those patients with positive IgA endomysium (EmA) antibodies displayed a marked improvement of their condition on a GF diet. (30)

The Gluten Connection

"In a limited sense, those who consume dairy proteins and gluten-containing foods put themselves at risk of brain fog since the blood brain barrier does not seem to bar these peptides from the central nervous system." (31) In fact, some clinicians believe that no one can digest the protein "gliadin" found in gluten grains. In an attempt to break down gliadin, our bodies attach an enzyme to it that actually stimulates an autoimmune reaction, causing CD in a large number of people. (32) More often, this process causes sub-clinical CD leading to a variety of chronic health conditions including decreased pancreatic function, decreased output of insulin and digestive enzymes, blood sugar dysregulation problems such as hyper- or hypoglycemia, digestive disorders and a variety of other health complaints. (33)

Autoimmune Disease & the Gluten Connection

Recently, an elevated level of a human protein called "Zonulin" was found in CD patients. (34) Zonulin is known to cause a hyperpermeable intestinal lining, often called Leaky Gut Syndrome (LGS). LGS allows metabolic and microbial toxins of the small intestines into the blood stream. Zonulin and LGS appears to be a contributing factor in CD as well as other Autoimmune Diseases. Interestingly, Zonulin levels diminish on a GF diet.

According to Dr. Cordain, there is strong data to suggest that the "foreign" antigens, which get into the bloodstream through LGS, may be involved in autoimmune diseases. Through a process called "molecular mimicry," these antigens contain certain amino acid sequences that have the same structural form as a variety of amino acid sequences in our body tissue. The immune system recognizes these large particles as foreign substances and makes antibodies against them, resulting in an autoimmune reaction against the similar body tissue.

This process has been implicated in rheumatoid arthritis from cow's milk. The inflammatory autoimmune reaction occurs in the joints because the amino acids found in human collagen are the same as in the amino acids of bovine albumin in cow's milk. (35) Also, a clinical observation after wheat ingestion of rheumatoid arthritis sufferers is followed within hours by increased joint swelling and pain. (36) The researchers suggest that one of the mechanisms involved is a permeable gastrointestinal tract to antigenic proteins or peptide fragments, derived from digested gluten. Inflammatory arthritis as well as Crohn's disease sufferers have been found to have inflammation of the intestinal tract that results in increased permeability. (37)

The incidence of CD in various autoimmune disorders is increased 10 to 30% in comparison to the general population. (38) Some of the autoimmune diseases associated with CD are Type 1 Diabetes, Rheumatoid Arthritis, Sjogren's Syndrome, Autoimmune Thyroid Disease, and possibly Addison's Disease, Crohn's Disease, Multiple Sclerosis, Thrombocytopenic Purpura, as well as others. Researchers recently found that diabetes and thyroid related antibodies in CD patients disappeared after the patient is put on a GF diet. (39) "These results contradict earlier studies that suggest the presence of organ-specific autoantibodies was due to a second autoimmune disease." They suggest that a GF diet started early may prevent the other autoimmune diseases frequently associated with celiac disease. In fact, it has been shown that the longer someone with CD is exposed to gluten, the higher the prevalence of other associated autoimmune disorders. (40) Funda et al. showed that a GF diet both delayed and to a large extent, prevented diabetes in NOD mice that have never been exposed to gluten. (41) Dr. Edward Hoffenberg suggests, "therefore, gluten may be able to drive the immune system, even outside the gastro-intestinal tract, to cause other diseases that we don't call CD, but may still be gluten derived diseases." (42)

Genes or Grains?

It is interesting to note that although CD is often linked to a specific genetic predisposition, it is observed primarily in countries consuming a wheat-based diet and is rare in China and Japan where rice is the main staple. (43) "The world distribution of celiac disease apparently relates to the consumption of gluten-containing cereals. ("44) Multiple Sclerosis (MS), another autoimmune disease, has often been correlated with the geography of the disease sufferer. Alter et al. suggested that it might be more correlated with the geography of cereal cultivation, that has a higher prevalence in wheat and rye growing areas, and less so in corn and rice growing regions. (45) In fact, there are several reports of remission of MS from a GF diet. (46-48)

Diagnosis

Most doctors base their recommendation for the avoidance of gluten on positive test results for CD. Serology tests for CD are used as a predictor of mucosal damage. They include the antiendomysial antibody, Iga, anti-gliadin, IgG and IgA, and tissue transglutaminase, IgA antibody tests. Although these tests are commonly used as diagnostic tools, a negative result for any one of these antibodies does not rule out CD. According to Dr. Peter Green, a Gastroenterologist and director of the GI Endoscopy Unit of Columbia-Presbyterian Medical Center in New York, "about 30% of Celiacs have negative antibodies at diagnosis. Therefore, the absence of positive antibodies does not rule out celiac disease. ("49) Also, once a person with gluten intolerance removes gluten from their diet, the antibodies disappear. This is a frustrating predicament for many who on their own accord make the decision to eliminate gluten from their diet. It takes at least 14-35 days of a gluten challenge to get a return of IgA antigliadin antib odies. Once they find that their condition improves on a GF diet, they either choose not to reintroduce gluten, can't eat enough of it, or eat it for too short amount of time to get the antibodies to reappear. In either case they cannot get a definitive CD diagnosis. Also, other gluten-related conditions do not have identifiable glutenrelated antibodies to test for.

For CD, the current Western Medicine "gold standard" procedure is a small intestinal biopsy to test for villious atrophy. This highly invasive test, unfortunately, has also been shown to give false negative results. "Endoscopic markers, themselves, have disappointing sensitivity even in a population at high risk of celiac disease...." (50) In a group of patients who had symptoms of CD, and tested positive for antiendomysial antibodies, showed no abnormalities of villous morphology upon biopsy. Their antibodies disappeared and symptoms improved on a GF diet. (51)

A test that has proved to be a sensitive predictor of CD but is not used very often, is the rectal gluten challenge. Troncone et al. studied children with CD and their siblings using a rectal challenge with a digest of gliadin. This study showed that the rectal gluten challenge identified 100% of patients with CD, independent of gene type. (52)

Other diagnostic tests which might be helpful in identifying gluten intolerance, is a urinary peptide for gliadorphin/caseomorphin test from The Great Plains Laboratory. This test measures the peptides from incompletely broken down pieces of protein from gluten and casein. It was initially developed by Dr. William Shaw for children with Autism. The Urinary Polypeptides Test from AAL Reference Laboratories tests for TAG, Casomorphine, Gladomorphin, as well as other peptides. Great Smokies Laboratory offers an Intestinal Permeability Assessment, which directly measures the ability of two non-metabolized sugar molecules, mannitol and lactulose, to permeate the intestinal mucosa, showing increased permeability.

Although this article focuses on gluten, patients with these various disorders might also benefit from the elimination of other foods, which might be contributing to health related conditions. Some of the more common troublesome foods are wheat, dairy, nuts, corn, soy, and shellfish. In fact, any intestinal inflammation of any etiology, if severe enough, can cause villous atrophy.

Results of Undiagnosed Gluten Intolerance

For children, the discovery of a gluten-related problem is of the utmost importance. Undiagnosed children may not grow and develop properly. The brain development that takes place in childhood may not occur due to the associated malabsorption or maldigestion. Also, opioids permanently affect the permeability of the brain barrier and inhibit brain growth during adolescence.

Although most of the research on undiagnosed gluten intolerance is on CD, the consequences are enormous for all gluten related conditions due to a higher risk of problems such as osteoporosis, intestinal lymphoma, infertility and miscarriage, short stature, etc. Results of undiagnosed CD also include splenic and pancreatic atrophy, thyroid disorders, gall bladder disorders, kidney disease, liver abnormalities, and impaired organ function. According to a study conducted by Dr. Giovanni Corrao, the death rate among people with CD is double that of the normal population. (53)

An Epidemic

Dr. Joseph Mercola suggests gluten intolerance is a very common condition that affects a considerable proportion of the population. "Recent research has put the figure as high as 1 in every 33 people, but my experience tells me that it is more like 1 in every 10 people.,, (64) Ron Hoggan calls it the "Plague of the 20th Century." Many who suffer from gluten intolerance do not know it. In fact, the current requirement of a diagnosis of Celiac Disease with a positive, small intestinal biopsy, in order to be considered "gluten intolerant," is actually harmful for the entire population. Our diagnostic tools are currently inadequate to uncover all of the conditions that gluten intolerance underlies or contributes to. Not only are those with CD being misdiagnosed but other diseases are being ruled out as gluten-related conditions, due to inaccurate and inadequate diagnostic techniques.

The influence of drug companies has also distracted many researchers away from studying how "diet" affects many conditions. Most research funding comes from the pharmaceutical industry who is interested primarily in the profit from new and patented drugs. Unfortunately, this is keeping many doctors and patients in the dark as to just what might improve their health.

Until more research is conducted and doctors are educated on the enormous impact of gluten intolerance, many more people will remain ill. For those who are suffering from debilitating or deadly conditions, this is a tragedy that must be remedied.

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Correspondence: Stacy Astor Shaul

Email: sastorshaul@hotmail.com

COPYRIGHT 2002 The Townsend Letter Group
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