The associated health issues related to gluten intolerance (GI), have a wide range, with Celiac Disease being the defining and best known aspect of that problem. However, GI can often go undiagnosed, because it does not always present with the more obvious symptoms seen in Celiac Disease (CD). GI and even CD can be cryptic, or a hidden problem, in many individuals. Gastrointestinal symptoms, such as diarrhea, abdominal pain, bloating, fatty stools, nausea or vomiting, and distention are at times part of the clinical presentation of GI and CD, however these symptoms may be mild or absent altogether. Cryptic or hidden GI, is commonly referred to as sub-clinical gluten intolerance or sensitivity, and bears distinguishing it’s clinical features from CD.
Gluten Intolerance-Celiac Disease
The exact mechanisms in Celiac disease (CD), are complex and not completely known. What is generally accepted to be the primary course of CD, involves the effects of gluten on the intestinal structures and immune system. There is perhaps no other such complex biological disease that has such a simple answer-the avoidance of gluten. Nevertheless, the understanding of the inter-related processes of gluten intolerance and CD, gifts us with insights into the dynamics of the intestinal milieu and subsequently a better grasp as to the workings of an amazing universe within-our digestive tracts.
Heathy Villi Damaged Villi Destroyed Villi
Enyzyme deficiency (peptidase) in gluten intolerance was once theorized to play a role in the development of CD. Peptidases, are protein digesting enzymes secreted by the intestinal tissues (brush border), and are distinguishable from pancreatic enzymes that also break down proteins for absorption. More recent research in enzyme therapy and CD, reveals that enzyme therapy with newer enzyme products demonstrate a promising role, in at the very least, ameliorating gluten intolerance (GI) reactions and perhaps buffering the margin of error in a gluten free diet. In numerous studies, pancreatic insufficiency (enzyme production) has been noted in a considerable percentage of celiac patients, and could in part explain why a population of celiac patients do not do as well despite eliminating gluten from the diet.(3) Enzyme therapy in part protects patients with CD with amelioration of symptoms related to gluten intake.(4) Enzyme therapy can provide important digestive support, and offer some protection for all CD patients where the gluten status of the meal is uncertain, as when eating out, or for those who are especially sensitive to gluten. Specific enzyme derivatives, demonstrate enhanced gluten digest, and shows promise in management of GI. Enzyme products that contain Aspergillus niger (fungal) derived enzymes, survive stomach acid and pepsin degradation, and effectively break down gluten proteins.(5) However, to date Aspergillus niger derivatives specific for gluten digest are not commercially available.
The Lectin Connection
According to another theory, a component in wheat gluten, wheat germ agglutinin (WGA), may act as a lectin with toxic properties to the intestinal cells. Lectins, are specialized proteins that bind specifically to sugars or other carbohydrates, usually on other proteins, which are located on the membranes of cells. They are thus often referred to as carbohydrate-binding proteins. Lectins causes cells to agglutinate, or stick to each other, compromising their function. In the digestive tract, lectins bind to specialized intestinal cells (crypt cells).(10) If they enter the blood stream, they also bind to red blood cells causing agglutination or clumping. High levels of lectins may be found in grains, the legume family (beans, peanuts), dairy and plants in the nightshade family. While lectins are present in most foods, their higher levels in some, are problematic for many individulas that are genetically vulnerable to their potentially toxic effects. “Lectins are (a) toxic, inflammatory, or both; (b) resistant to cooking and digestive enzymes; and (c) present in much of our food.”(11) Among the effects observed in the small intestine of lectin fed rodents is stripping away of the mucous coat lining the intestinal tract, increased intestinal permeability (leaky gut), and the overgrowth of toxic bacteria and.(12,13,14). The characteristic damage from gluten intolerance (crypt hyperplasia), to the intestinal tissue, is also caused by WGA.(15)
In examining the details of a food intolerance like gluten, it is a logical course to look at the known pathways of the immune reactions, intestinal anatomy and function, the genetic characteristics of predisposed individuals, and the unique construct of gluten containing grains. Nevertheless, all of that examination does not entirely reveal why some genetically gluten intolerant individuals never develop celiac disease (CD), why some celiac disease patients do not recover even after eliminating gluten from the diet, or why a few (rare) without the genetic blueprint, manage to become “intolerant”. The answers to these questions, may come from a deeper examination as to the factors that may “break” a gluten tolerant individual, into an intolerant pattern - it is the proverbial straw that broke the camel’s back.
Gluten Intolerance-Related Conditions
The prevalence of CD in general Western populations is close to 1% and is somewhat higher in certain Western European populations.(21) Estimates will vary depending on the populations studied as evidenced by the following numbers:
PREVALENCE OF CELIAC DISEASE IN THE UNITED STATES (22)
In average healthy people: 1 in 133
In people with related symptoms: 1 in 56
In people with first-degree relatives (parent, child, sibling) who are celiac:1 in 22
In people with second-degree relatives (aunt, uncle, cousin) who are celiac: 1 in 39
Estimated prevalence for African-, Hispanic- and Asian-Americans: 1 in 236
Many experienced practitioners think that the rate of gluten intolerance (GI) is much higher, particularly since many individuals are diagnosed as having primarily other related disorders, and so many others are probably never diagnosed with an intolerance or a sensitivity. More often, the intolerance to gluten causes sub-clinical celiac disease (CD), or CD that is not more readily apparent by it’s classical clinical symptom presentation, leads to a variety of chronic health conditions including osteoporosis, anemia, type 1 diabetes and depression. Researchers are also beginning to see a connection between gluten GI, and neurological disorders. Gluten sensitivity can be primarily and at times, exclusively a neurological disease, without the presence of intestinal damage.(24) Unexplained neurological dysfunction may comprise up to 10% of of GI cases.(24) Autism,(25) Down’s Syndrome,(26) and epileptic disorders,(27) to one extent or another, are associated with GI. In children, “softer” neurological problems associated with celiac disease (CD), include ADHD, developmental delay, chronic headache, and abnormally low muscle tone (hypotonia).(28) In Autistic Spectrum Disorders and ADHD, morphine-like exorphins (substances having opiate-narcotic like activity), derived from the incomplete breakdown of grains and dairy, alter mood and behavior by depressing serotonin, dopamine and norpinephrine levels. 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 without the typical autoimmune response, as seen in CD.
Leaky Gut Genes
Celiac disease is also known to cause increased permeability of the intestine through the inflammatory processes that occur in gluten intolerance. Commonly referred to as “leaky gut”, Leaky Gut Syndrome is a disorder in which the intestinal lining is more permeable or porous than normal. Apart from factors like inflammation, there are genetic factors that predispose individuals with CD to having a more permeable intestine. Zonulin, a protein that influences the integrity of the intestinal wall through a regulatory function, has recently been identified as playing a key role in CD and other autoimmune disorders.(41) Individuals with celiac disease have higher levels of zonulin, leading to a higher degree of leaky gut, and allowing gliadin to permeate between the normally tight junctions of the intestinal cellls. A component of the immune reactivity associated with CD, is dependent on the passage of gliadin peptides through the intestinal barrier where a component of gliadin/immune cell cross reactivity occurs. So, you have gliadin slipping through a more permeable membrane, in part by the influence of increased zonulin release, which is integral to the eventual disease process typical of CD.(42) Another genetic link, is the discovery of another genetic variant involved in the maintaining the tight junctions of the intestinal barrier (myosin IXB variant) which further empasizes the connection of a leaky gut mecahnism as a primary process in celiac disease.(43) The leaky gut pivot to GI and CD is undoubdetly a factor not only in CD, but also in the neurological, rheumatological and other autoimmune disoders that are comorbid (coexisting) conditions in CD. After one weighs the various gene influences in GI and CD, it is hardly a stretch to conclude that perhaps a series of genetic factors combine together to influence the gamut of gluten intolerance related disorders and CD.
There is currently no test for diagnosing celiac disease with 100% certainty. Most doctors base their recommendation for the avoidance of gluten on positive test results for CD. Serology (blood) tests for CD are used as an indicator of gluten stimulated immune reactions, and a predictor of damage to the mucosal barrier-the intestinal wall. They include:
Of the latter two antibody assessments, indicators of immune mediated inflammation and damage to intestinal tissue, the tTG antibody IgA test is now considered by many practitioners, the preferred marker for diagnosis, although the research literature is rife with elder references to the superior value of the anti- endomysial antibody marker. There is evidence to support using the tTG antibody test as an accurate alternative to the anti-endomysial antibody test.(44) A new convenient option for the clinician looking to evaluate a possible GI or CD condition, are blood testing kits that can be done in the office. There is now available “in office” test kits, with proven efficacy, for tTG/IgA antibodies.(45)
The genes that are screened for in genetic testing for GI and CD were previously mentioned above-HLA genes-HLA-DQ2 (DQA1*0501/DQB1*0201) and HLA-DQ8 (DQA1*0301/DQB1*0302). The HLA-DQ2/ DQB1*0201 incurs increased risk. The logic for genetic testing for CD has a couple of rationales. The first is to “rule out” a genetic predisposition to CD. This is a useful strategy when an individual is exhibiting some of the problems associated with GI and any of the various forms of CD, but the blood antibody tests are negative and a biopsy is not possible or desired. The antibody and gene markers are often ordered as a comprehensive panel of tests to weigh all the possible indicators. Without these core gene influences, it is considered rare that the individual with a negative gene test will develop celiac disease in the future. People who test negative for the gene would essentially rule out any possible link to GI and CD and could eliminate regular testing and screening for the remainder of their lives. A negative gene test in context of a suspected celiac, or celiac related case, would then rule out the probability of CD, and the various celiac related diseases, and shift the investigation to another diagnosis. Another advantage in gene testing, is the screening of children of parents with a history of GI or CD. A gene test for children of an adult with such a history would provide invaluable dietary guidelines. Positive results would allow the parents to know which children need close monitoring. A convenient and viable screening for celiac genes that is ideal for testing children and adults, is a cheek cell specimen (buccal swab) test that is offered by Enterolab. The buccal swab gene test can be done at home and bypasses the needle trauma that very young children fear and abhor. In all cases, a positive gene test is not specific to, nor does it diagnose CD. Nevertheless, it does increase the likelihood, if positive, that either GI is potentially a health threat, or that indeed, CD may be present if there is supporting clinical indications, and positive antibody assessments. It places an individual into an “at-risk” group for celiac disease, and provides leverage for prudent dietary choices as well as the need for future screening. Only 3% of individuals that carry the HLA celiac markers, HLA-DQ2 or HLA-DQ8 develop celiac disease, which infers that HLA gene testing, even if positive, is not a perfect predictor of risk for CD and that there are multiple gene influences, including the “leaky gut” genes detailed earlier.
* Having this combination of HLA type genes, predisposes an individual to a higher risk of developing type 1 diabetes. Inheriting the HLA-DR3 gene from one parent and the HLA-DR4 from the other parent, he/she will have an HLA type described as DR3/DR4.
** The immune system uses the HLAs to differentiate self cells and non-self cells. Any cell displaying that person’s HLA type belongs to that person (and therefore is not an invader). Any cell displaying some other HLA type is “not-self” and is an invader. HLA types are inherited, and some of them are connected with autoimmune disorders and other diseases. People with certain HLA antigens are more likely to develop certain autoimmune diseases, such as Ankylosing spondylitis, Celiac Disease, SLE (Lupus erythematosus), Myasthenia Gravis, and Sjögren’s Syndrome.http://en.wikipedia.org/wiki/Human_leukocyte_antigen
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