Celiac Disease
Genes plus Grain equals Misery

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Celiac disease (CD), according to eMedTV, affects 1 in 133 people in the U.S.; others say 1 in a 100.  Whatever it is, it's about 2 million people. Are you one of them? 

How serious is coeliac disease, as it is sometimes spelled?  Does potentially fatal sound serious enough?  
  
By way of definition, CD is an autoimmune condition that hits the small intestine and can occur at anytime throughout one’s life.   It's not something we can catch; that is, it's not transmissible or contagious. 

We have to have the right genes, or should we say the wrong genes, in order to be a celiac sufferer.  So far it is incurable and is a lifelong affliction.

Note:  The "No Wheat" symbol above right is a link to the Glutenfreemall.com website where an incredible selection of gluten-free products are offered.  Take a look.

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Gluten

Gluten is the culprit in celiac disease and it is everywhere.   It is a protein component of wheat, rye, barley and occasionally oats are implicated.

Gluten is produced in grains by gliadin, a glycoprotein, and the protein glutelin.  They are joined by starch and found surrounding the embryo in the seeds of grass-related grains.

Besides occurring naturally in certain grains, another reason that gluten is so prevalent in our food supply is that it plays a very important role in food processing. 

Gluten is what causes dough to be elastic, allows it to rise and gives the final product, bread or pastry for example, a chewy texture.  The more refined the gluten is, the more chewy the product; think of pizza crust and bagels.  

Since gluten is not soluble in water, it is removed from flour by kneading it into dough then washing out the starch with cold water. 

Then the gluten is put through a screw press to remove about two-thirds of the water then dried in an oven to remove the rest of the water.  The purified gluten is then sifted, milled and packaged. 

Purified gluten is used in commercial baking, production of imitation meats, added to foods to increase protein content and added to any foods, such as ice cream, where stabilization is required.  Gluten is used extensively in pet foods as a protein 
additive.

The You Tube video below is from the Mayo Clinic and features gastroenterologist and celiac disease specialist Joseph Murray, M.D. describing the findings of their research. It was published July 1, 2009 in the journal Gastroenterology and concerns the increased prevalence of celiac disease and the higher mortality for people who have celiac disease but don't know it.



Symptoms

For gluten-sensitive individuals, consuming foods containing gluten causes some very unpleasant reactions.  The upper region of the small intestine, the duodenum, is the most common site for a gluten induced autoimmune reaction.

Diagnosing celiac disease can be difficult since symptoms can differ greatly from person to person and the list of signs and symptoms are extensive.

Typical symptoms include bloating, gas, indigestion, abdominal pain, constipation or diarrhea (which can be ongoing or occasional), nausea, vomiting, lactose intolerance (very common with celiac disease), decreased appetite, weight loss, and stools that float, are fatty, foul smelling or even bloody. 

Because of the malabsorption of nutrients there are a host of collateral health issues.  Celiac disease can cause delayed growth in children, muscle cramps and joint pains, mouth ulcers, tingling in the hands or feet, nosebleeds, fatigue, depression, hair loss, missed menstrual periods, and seizures.  

Are we getting an idea why a diagnosis might be so difficult?  Most doctors who are unfamiliar with Celiac disease will typically start down the road of eliminating one cause, then another and another and might eventually arrive at a wheat induced autoimmune reaction as the real culprit. 

For each symptom mentioned above, there are numerous possible  causes.  Common misdiagnoses include diverticulitis, Crohn's disease and irritable bowel syndrome plus, according to Dr. Mark Hyman, about 52 others.  The embedded YouTube video below is Dr. Hyman's explanation of gluten caused celiac disease; uploaded by Dr. Hyman's Ultrawellness on Jan. 5th, 2010 under the standard YouTube License. 

It is worth investing the seven minutes or so to watch it along with the other videos shared here on this very misunderstood condition.



If Dr. Hyman's video peaked your interest, here is a transcript of his Gluten: What You Don't Know Might Kill You video.

Good to keep for reference.

Anytime we get a diagnosis described as a syndrome, it just means the doctors have no idea what is causing it.  

In fact misdiagnosis of celiac disease is rampant and every celiac will have a list of personal horror stories concerning their ordeals prior to receiving a proper diagnosis.

It affects more women than men, more Caucasians than other racial types and more people of European descent.

Testing for Celiac Disease

If anyone is experiencing symptoms of gluten sensitivity described above, it could save a lot of aggravation and time to tell their doctor to order the blood test for the presence of the antibodies associated with gluten intolerance.

Otherwise, the doctor will probably start the diagnosis by trying to eliminate all the more common causes for those symptoms.

The antibodies that the test is looking for are the tTGA (antitissue transglutaminase antibody) or EMA (anti-endomysium antibody). 

If the test comes back positive for either of those antibodies the next step will probably be a biopsy of the duodenum using an endoscope.  If celiac disease is present, the biopsy will show a flattening or shortening of the villi. 

Villi are the microscopic "fingers" that line the interior of the intestinal walls and serve to vastly increase the surface area to maximize nutrient absorption. 

By lying down on the job instead of standing tall, absorption of nutrients is essentially stopped.  It is almost as if the body recognizes gluten as something harmful and reacts by putting out the "No Admittance" sign.

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Treatment

Once an accurate diagnosis is made of celiac disease, treatment largely consists of a lifelong avoidance of foods containing gluten.  Since the medical community loves abbreviations, the standard of care is called GFD or "gluten free diet". 

There is no shot, vaccine or prescription pill that will cure celiac disease.

Since there is no cure so far, much of the treatment is focused on controlling the symptoms.  Mayo Clinic's experience is that up to half of celiac patients intestinal damage doesn't heal completely even with the GFD.  

Thus people with celiac disease should be monitored closely and when diet alone isn't effective, steroids and immune-system suppressors may be prescribed to control intestinal swelling and malabsorption of nutrients.

Another irritating symptom of celiac disease is an itchy, blistering skin rash called dermatitis herpetiformis.  A skin test will be made to confirm the condition and then a drug, most likely dapsone, will be prescribed in conjuction with the gluten-free diet.  

Since it is an autoimmune disease, the first reaction of the medical community will be to prescribe a drug to suppress the immune system.  The problem is that a suppressed immune system opens one up to a host of other medical conditions. 

It seems that instead of suppressing the immune system, why not use a natural polysaccharide from the aloe vera plant to modulate the immune system.  This is an area that should be reseacrhed in the context of celiac disease.

Since the occurrence of gluten sensitivity is only 1 in a 100 or so, maybe the commercial market for a cure doesn't scream of urgency.  At any rate, another area for research would be genetic engineering to see if the two genes linked to celiac disease could be turned off.
 
One other thought is whether or not the immune system itself could be trained not to create the antibodies that attack the gluten protein.  

There are several natural substances in dietary supplement form that enhance the cells signaling or communications.  It would be great if the intercellular signaling process could be altered to recognize the gluten protein as a "friendly" instead of an invader. 

Dietary Sources of Gluten

In general any food containing wheat, rye or barley will contain gluten.  If we train ourselves to read food labels, it quickly becomes apparent how ubiquitous gluten really is.  If gluten is present in a food, the label will usually list gluten as an ingredient or carry the phrase, "contains wheat".   

Think about what is made from wheat flour.  For starters, that would include all bread, muffins, cakes, cookies, pastries, pasta, pizza crust, breakfast cereals, breading used for deep frying.  It even includes things like ice cream and condiments like ketchup since gluten is used as a stabilizing agent in these products.  

If that's not enough, beer could cause celiacs some real problems due to the malt content.  The good news is that completely distilled alcohol such as whiskey, bourbon and gin are considered "safe".  Wine, rum, tequila and sake are generally safe since they are not distilled from the toxic grains associated with celiac disease.

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Another gotcha is the imitation meats used in vegetarian diets.  Wheat gluten is the basis for imitation beef, chicken, pork, fish and duck. 

It turns out that when gluten is cooked in the broth of basic meats, it absorbs the surrounding liquid, including the meaty taste, and becomes firm to the bite; not like real meat but close enough. 

If vegetarians are eating imitation meats through a desire not to contribute to the slaughter and consumption of animals, it is likely that they are still eating animals via the broth of the meat stock.

It is also possible that some medications have the gluten protein in them.    

The embedded You Tube video below is a discussion of Celiac Disease on the View. It is a little over 7 minutes long and is included here just to illustrate that CD is finally starting to get the attention it deserves.


Genetics, Pathology and the Leaky Gut 

From here on it's going to get a little deep in the science department with terminology that may be unfamiliar to the non-celiac. 

Anyone who has been diagnosed with celiac disease will likely be very familiar with the following description.  Anyone who has that innate desire to understand why things happen and how they happen, read on.  Otherwise feel free to click out and move on to the another topic. 

A good starting point is to ask how celiac disease harms the body.  The big picture explanation is that it damages the villi lining the small intestine resulting in an inability to properly absorb vital nutrients, a condition known as villous atrophy.  The autoimmune reaction to the gluten protein causes the villi in the small intestine to flatten out or become truncated (shortened).

Gluten is not usually a protein that would cause an immune reaction since it does occur naturally in grain and humans have been consuming it for centuries. 

But for about 1 in 100 people in the U.S., genetics come into play and at least two gene variants raise havoc with the upper gastrointestinal system when encountering gliadin, the gluten protein in wheat.

By way of a memory refresher, humans have 23 chromosome pairs with 24,000 or so genes residing on those chromosomes.  Genes contain our DNA which consists of four bases designated as A, T, G and C.  Bases A and T are joined and bases G and C are joined in the familiar double helix arrangement where A/T or G/C linkage is called a base pair.

Our chromosomes are numbered 1 through 22 with the 23rd being the sex chromosome, either X (female) or Y (male).  In considering celiac disease, we are concerned with chromosome 6. 

It has over 2,000 genes and around 170 million base pairs.  Genes are designated by cryptic letters and numbers that mean something to a geneticist but not much to the rest of us. 

The genes on chromosome 6 that are thought to predispose one to celiac disease are labeled HLA-DQ2 or HLA-DQ8. 

HLA stands for "human leukocyte antigen” and is part of a system called the "major histocompatibility complex system" or MHC.  This is the system that is concerned with distinguishing between self and non-self cells in the immune 
system. 

Celiac sufferers have a form, or allele, of the DQ2 or DQ8 gene which forms receptors that bind to the gliadin peptides (gluten protein) much tighter than other forms of the antigen-presenting receptor in the MHC system.
 
The effect is that these two forms of the DQ gene tend to activate T lymphocytes and start the autoimmune process.  T lymphocytes are white blood cells that play a central role in an aspect of immune response that does not depend on antibodies. 

Rather, they activate macrophages, natural killer cells and antigen-specific cytotoxic T-lymphocytes while releasing various cell-signaling regulators called cytokines that play a major role in inter-cellular communications.

One of the big mysteries was how a large molecule like gluten got through the intestinal membrane and into the immune 
system in the first place.  It turns out that a part of the wheat protein gliadin stimulates membrane cells to open up and allow larger molecule to get through the sealant between cells.  

It's similar to the seals in a pump or transmission in a car going bad and allowing fluid to leak through.  

Current research indicates that cell membrane leakage is very likely the result of gliadin binding to the CXCR3 receptor gene causing an accelerated release of the protein zonulin. It is significant that increased levels of zonulin are seen in celiacs.  

Zonulin can be thought of as a traffic director or gatekeeper for the body's tissues.  Higher levels of zonulin increase the permeability of tissue membranes thus allowing gluten and other allergens to get access to the immune system.  As an aside, zonulin plays a vital role in the integrity of the blood-brain barrier membrane.

While we are tossing numbers around, this is a good place to introduce one of the Great Courses on  Understanding Genetics: DNA, Genes, and Their Real-World Applications.

It is not about Celiac per se, but does give one an excellent understanding of how genes play into the picture.  Click on the Great Courses button below, enter Understanding Genetics in the search box and  see if it is for you.



The leaky gut in celiac's lets the gliadin peptides penetrate the cellular membrane and triggers both the innate immune system as well as the adaptive immune response.

The innate response stimulates the release of inflammatory chemicals via the immune system signaling process.   

The adaptive immune response is stronger in that it allows the DQ2 form of the gene to be altered by an intestinal enzyme, transglutaminase. 

Anti-tissue-transglutminase antibodies in the enzyme tissue 
transglutaminase (tTG) are detected in most cases of celiac disease.   TG changes the gluten proteins into a form that
stimulates the immune system more effectively causing autoantibodies to attack tissue transglutaminase.

There is much more to the manifestation of celiac disease than was described above but the complexity is more than we 
want to continue with here.  The reader is invited to examine the list of recommended books below if a more in-depth examination of the current science is needed.  

Food for Thought

Some of these ideas for research were touched on above but they bear repeating. 

Might there be other ways to deal with one's celiac disease other than GFD, the gluten free diet, meaning the total avoidance of food containing gluten?  Maybe there is.

Some of these ideas for research were touched on above but they bear repeating. 

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Looking at the sequence of events in celiac disease, there may be several points at which the reaction could be stopped.

First is that our genetic makeup must contain the HLA-DQ2 and DQ-8 genes that cause the body to react to gluten.  We can't choose which genes we inherit and we can't just remove the offending genes from our chromosomes.  

But what if a way were found to stop the HLA-DQ2 or DQ8 
genes from expressing, that is, reacting to gluten; keep them asleep as it were?

Second, the gluten protein reacts with the CXCR3 receptor gene to trigger the release of excess zonulin.  This is what increases the permeability of cell membranes giving the antigen access to the immune system. 

What if a way were found to prevent the gliadin peptide (gluten protein) from binding with the CXCR3 receptor and thus keep zonulin levels normal and keep the cellular membrane intact. 

This should inhibit the access of the offending protein to the circulatory system and thus the immune system.

Third, the innate immune system recognizes the gluten protein as a threat and activates the immune systems army of T-lymphocytes, macrophages, NK cells and cytokines.

What if a way were found to make the immune system ignore the gluten protein and recognize it as just another normal food protein and not a threat? 

Then there would be no immune signaling, no attack, no inflammation, no damaged villi, no malabsorption and no celiac disease symptoms.

Concurrently, the adaptive immune system changes the gluten proteins into a form that causes antibodies to attack tissue transglutaminase. 

What if a way could be found to stop the transformation of the DQ2 gene by the transglutaminase enzyme and thus stop the creation of antibodies to tissue-transglutaminase? 

Then there would be no adaptive immune response and no destruction of tissue.

Recommended Celiac/Gluten Reading List

1. Celiac Disease, Second Edition: A Guide to Living with Gluten Intolerance

2. Dangerous Grains: Why Gluten Cereal Grains May Be Hazardous To Your Health

3. Celiac Disease (Revised and Updated Edition): A Hidden Epidemic

4. The Best-Ever Wheat and Gluten Free Baking Book: 200 Recipes for Muffins, Cookies, Breads, and More, All Guaranteed Gluten-Free!

5. The Gluten Connection: How Gluten Sensitivity May Be Sabotaging Your Health - And What You Can Do to Take Control Now

6. Gluten Toxicity: The Mysterious Symptoms of Celiac Disease, Dermatitis Herpetiformis, And Non-Celiac Gluten Intolerance

7. The Gluten-Free Kitchen: Over 135 Delicious Recipes for People with Gluten Intolerance or Wheat Allergy

8. Coeliac Disease: Nursing Care and Management (Wiley Series in Nursing)

9. Gluten-Free Food Science and Technology

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