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    Ten Facts About Celiac Disease Genetic Testing


    Dr. Scot Lewey

    Celiac.com 04/24/2008 - Genetic tests for celiac disease and gluten sensitivity are readily available. Testing can be performed on either blood and mouth swab samples. If the testing is performed by certain laboratories not only will you have quite an accurate prediction of your risk of Celiac disease but also you may have information about the statistical probability that your children will inherit the risk, your likelihood of more severe Celiac disease, whether one or both of your parents had the risk gene, and for some laboratories you may determine your risk of gluten sensitivity without Celiac disease.


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    The absence of any portion of the high-risk genetic patterns DQ2 and DQ8 nearly excludes the possibility of celiac disease with an approximate accuracy of 99.9%. However, there is a big caveat about relying on "negative celiac genetic testing". To definitively declare you have negative celiac genetic tests requires that the laboratory test for and report the presence or absence of the entire HLA DQ genetic pattern, including both alpha and beta subunits. The DQ genetic patterns DQ2 and DQ8 have two subunits but some laboratories only test for the beta subunit. This DQ typing is complicated and difficult to understand even by physicians and scientists. I have written an updated detailed review that appears in the Spring 2008 issue of Scott-Free newsletter published by celiac.com.

    Data collected by Dr. Ken Fine of Enterolab has supported the well-known fact that the absence of DQ2 and DQ8 does not exclude the risk of being gluten intolerance or sensitive though it now generally believed that one or both of those genetic white blood cell patterns are required to develop the autoimmune disorder known as Celiac disease or Celiac Sprue. However, there is a new study that reports that being negative for DQ2 and DQ8 does not completely exclude the possibility of celiac disease, especially in men. Previous studies have well documented blood test negative Celiac Sprue, also more common in elderly men with long-standing severe disease. Since DQ2 or DQ8 is almost universally present with the specific blood tests tissue transglutaminase and anti-endomysial antibodies are present it is not surprising that individuals without DQ2 or DQ8 that are negative for these two blood tests are being reported that meet criteria for Celiac disease.

    These new studies are also providing further information that the genetics of Celiac is gender specific. If you are a man, your risk of celiac disease may be higher than a woman if you don't have the classic genetic patterns. Again, in this situation your blood tests may be negative. If you are a woman, the risk for Celiac disease is generally higher than a man, especially if you have received the at risk gene from your father instead of your mother.

    Celiac is arguably the most common autoimmune disease. It is very common. It is easily treated. It affects 1/100 people worldwide. However, most people with celiac disease (~90%) are unaware, undiagnosed or misdiagnosed. Most adults finally diagnosed with celiac disease have suffered at least 10-11 years and have seen more than 3 or more doctors. Genetic testing is not only available but can be extremely helpful in determining your risk of developing Celiac disease, how severe it may be and the risk of your family members. Don't be one of those whose diagnosis is missed or needlessly delayed for over a decade. Get tested! Learn about the genetic tests for Celiac disease and if necessary educate your doctor about this testing.

    Here are ten facts you should know and remember about Celiac genetic testing.

    1. Genetic testing can help determine your risk as well as your children's risk.
    2. Celiac genetic tests can be done on blood or a mouth swab sample but your doctor may be unaware of the tests, not know how to order them, or know how to interpret the results.
    3. Genetic testing is not affected by diet. You can be eating gluten or on a gluten free diet. Blood tests for celiac disease antibodies, however, need to be done while eating gluten. They can become negative within a few weeks of restricting gluten so if you are going to get the diagnostic antibody blood tests don't begin a gluten free or restricted diet before being tested.
    4. Some insurance companies do not for the Celiac genetic test and almost all who do require pre-authorization first. The following diagnostic codes are helpful when requesting insurance coverage: 579.0 (Celiac disease); V18.59 (family history of GI disease); and/or V84.89 (genetic susceptibility to disease).
    5. Some laboratories do not perform the all of the necessary components of the test to completely exclude the possible genetic risk of Celiac disease and most don't test for or report the other gluten sensitive DQ patterns. Before you accept that have a negative test you need to know if your test included both the alpha and beta subunits of HLA DQ or did they just perform the beta typing.
    6. In some rare individuals, especially some men, a negative genetic test may not exclude the possibility of celiac disease anymore than a negative blood test. Men more commonly have negative genetic tests and blood tests, especially older men with long-standing severe disease.
    7. Both the DQ type, and number of copies you have, matter when determining not only your risk but also the possible severity of celiac disease. Two copies of DQ2 carries more risk than one copy of DQ8 or only partial DQ2. Even a single copy of DQ2 alpha subunit ("half DQ2 positive") carries risk for celiac disease but most of the commonly used laboratories for Celiac genetics do not test for or report the presence of this component of the celiac genes.
    8. The absence of at risk genes DQ2 and/or DQ8 does not exclude the possibility of being gluten intolerant or sensitive. You may respond to a gluten free diet even if you don't have DQ2 or DQ8 or true autoimmune Celiac disease.
    9. You can get genetic testing without a doctor's order and the tests can be done without having blood drawn or insurance authorization if you are willing to pay between $150-400 (www.kimballgenetics.com and www.enterolab.com).
    10. Laboratories in the U.S. that are known to offer complete alpha and beta subunit genetic testing include Kimball Genetics, Prometheus, and LabCorp. Bonfils, Quest and Enterolab only test for the beta subunit portions and therefore their test can miss part of a minor alpha subunit that carries a risk of Celiac disease. A negative DQ2 and DQ8 report from these labs may not necessarily be truly negative for the risk of Celiac disease.
    References and Resources:
    • HLA-DQ and Susceptibility to Celiac Disease: Evidence for Gender Differences and Parent-of-Origin Effects. Megiorni F et al. Am Journal Gastroenterol. 2008;103:997-1003.
    • Celiac Genetics. Dr. Scot Lewey. Scott-Free, Spring 2008.


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    Guest Ann Stewart

    Posted

    Great info .........I never knew... always thought you had to have the intrusive biopsy test.

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    Guest Frances l Garcia,MD

    Posted

    Excellent: it explains why I am a severe celiac and yet am negative for the antibodies. I am a woman, northern European, Hispanic and Middle Eastern ethnicity and no previous known family history. My sons have tested negative for tTg and . My brother is negative for the tTg and antiendomyasial antibodies but has severe osteoporosis at 45 years of age, without any known risk factors. We need to do genetic testing!!

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    Guest Carina

    Posted

    Thank you. I need to get my kids tested, and I feel better knowing these things before I go in.

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    Guest Carri

    Posted

    Wow, very comprehensive yet easy to understand the 'genetics lingo.'

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    Guest sharon mackey

    Posted

    I had seven endoscopies done only 2 of them with same doctor---rest all different--celiac came back negative--also blood test---I finally found a celiac doctor whom my daughter recommended--she also has celiac disease--she did a cheek swap and sure enough I have celiac disease and have had it for a few years. I started having stomach problems and had a hernia and a sphincter that didn't close--so this was the problem with my severe bile reflux and gerd. I developed scurvy a year before that and it took 3 months for doctors and a specialist to try and find out what it was. I had it very badly on my whole right leg. Discolored-blood collections under the skin---the hundreds of red dots-due to very low platelets- All of the symptoms I had visible and not and no one put it together. I kept suggesting it was a problem with malnutrition but no one listened. My stomach and throat were raw. Had all kinds of tests done---finally my oncologist told me to have a leg biopsy done and sure enough it came back as scurvy. A lot of damage was done to my digestive system. Also had my gallbladder removed-had a small stone--they thought this might have been the source of the reflux --I ended up with worse reflux. It took me 2 years to find a surgeon to do the fundoplication--I am a high risk patient--allergic to many, many,drugs---pump prohibitors gave me seizures-so I am unable to take anything for the gerd. thought all would end there--I still have reflux severely---weigh 93 pounds with many food allergies--casein, yeast all dairy and it goes on----no rice-my blood counts and platelets are always bad--high calcium--cysts now found on my thyroid and most probe my parathyroid glands--didn't show any if the x-rays but I have all the symtoms-kidney stone--I only have one kidney--donated the other to my sister in 1968. I live in pain every day--trying to cope---your articles help me a lot. Thank you.

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    Guest European lady

    Posted

    I am a Northern European lady and have family history of gluten sensitivity, I am gluten sensitive but do not have DQ2 OR DQ8 AND had one doctor at Mayo clinic telling me that it is 100% certain that I can't have Celiac disease.

    A gluten-free diet put my intestinal symptoms on the right track.

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    Guest Mimi

    Posted

    Thank you for a novice friendly explanation of the genetic testing for celiac disease. I did not know about the alpha and beta-I only had one done.

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    Guest Linda Hays

    Posted

    It was very good and informative.

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    Guest Jean

    Posted

    Thank you for this article. It confirms suspicions that I had about family members in my family who probably have the disease and refuse to consider it. All members that I'm referring to have diabetes.

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    Guest LENA

    Posted

    I have a few concerns, I had a biopsy done in 10/08 and it tested negative for celiac disorder. However 7 months later I'm still having the same symptoms and now my doctor is saying that's not a guarantee (the biopsy) and there treating me as if I do have celiac now.

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    Guest julie

    Posted

    Could you please provide some theories as to why older men who test negative for the celiac risk gene can actually have celiac.

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    Guest disillusioned

    Posted

    Thanks a lot. I was going to go with Enterolab until I read this article. Now I plan on testing with Kimball or Labcorp. However, I couldn't find any info on Kimball or Labcorp's websites which mentions alpha and beta subunit genetic testing. Are you sure they still offer this? Has anyone else here gotten these tests done?

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    Guest Tara

    Posted

    I just ordered the tests from Kimball (after seeing the special they're offering right now through this website) and am eagerly looking forward to getting the test and hearing the results. My 2 sisters and I all are showing signs of gluten sensitivity, but none of us has been officially diagnosed yet.

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    Guest Richard

    Posted

    Very informative, as a scientist and a celiac I am amazed how complex the genetic marking of celiac disease is. I would even dare to say that it would be easier to look for a gluten-tolerant marker and use the non-presence of this marker as an indicator of gluten related conditions! However, I am even more amazed at the very un-scientific diagnosis process that many 'doctors' follow. Too many people are reporting multiple misdiagnoses and inaccurate testing regimes. As a researcher (astrochemist) I would not trust these 'doctors' in my lab!

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    Guest Monique

    Posted

    I'm Celiac (finally correctly diagnosed in 2001) and have a son (he's 15) that has tested positive for Celiac on one of the blood test. He's had 2 blood tests. The doctor didn't want to do a biopsy so I opted to do genetic testing. I chose Prometheus to do it. It cost $509 and the test came back 'inconclusive' for Celiac. Does anyone know what that means? My doctor said that means that my son may get Celiac and he may not. I'm not thrilled that I spent $509 to find that out. I already knew that!

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    Guest Barbara

    Posted

    Thank you for this article. I was recently diagnosed with celiac and could not figure out how I was going to get my kids tested (11 & 8 years) without a biopsy, especially as neither of them seem to have any real problems. This is a much better way of checking. My doctor uses Quest so will have to discuss either using one of the others or doing it myself. Thanks again!

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    Thank you for this very informative article.

    I am a self diagnosed Coeliac…

    I had all the “classic†symptoms but was misdiagnosed by all the doctors that I've seen over a 13 year period!

    I have a sister that was properly diagnosed as Coeliac at 9 months old. At 15 years old, I had severe Anemia that didn't respond to any treatment, Fatigue, Nausea, terrible abdominal pains, weight gain etc but the doctors convinced me (and not my mum…) that I didn't have Coeliac based on a negative blood test and endoscopy.

    Finally, at 28, when the stomach pain attacks grew too close together I insisted on another blood test- which came out positive

    On the advice of my GP, I skipped the biopsy and started a gluten-free diet straight away. I had immediate positive affect on my overall health

    Since then, my 2 kids have been genetically tested. As they carry 1 gene only, the official result was “Coeliac disease cannot be ruled outâ€

    I chose to put them on a strict gluten-free diet, based on my experience. I just had a 3rd child and not even going to bother testing this time….

    My concern is regarding the effect of the 13 year long exposure to Gluten on the risk of bowl cancer

    If anyone could point me to some information regarding that I would appreciate it

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    I'm so glad I read this article before choosing a lab. Turns out I have an alpha sub-unit that would not have been detected by labs only checking for the beta sub-unit.

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    Guest Shirley & Bob

    Posted

    Very interesting. I had a blood test yesterday and will wait for results

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    Guest Jeff Kelly

    Posted

    What I STRENUOUSLY object to in this article is the usage of the term "True Celiac Sprue." This is scientifically and practically a TOTAL MISNOMER. It persists in medicine because medical doctors have ZERO to fifteen minutes of training in Celiac Disease, and the so-called intellects in the field make this extremely artificial, unnnecessary, and wholly disparaging(to add to the already extant built-in disparagement in Celiac inherently)distinction in language that bears ZERO relation to REALITY. They do so in the name of science but cannot in fact justify their actions with sound comprehensive science, just as Lewey accurately acknowledges it is not possible to exclude a possible diagnosis of Celiac on the basis of negative genetic or blood antibody tests(or even BOTH those situations).

    On the positive side I do feel the article makes an important contribution to the gender designation generally supportive of the understanding that men have a harder time obtaining an affirmative diagnosis and some of the reasons for that--although one of the main reasons has nothing to do with medicine and everything to do with Sociollogic and even Socioeconomic factors in that society generally does not easily accept the notion that men should be designated easily as disabled or of a similarly suggestive adjective with regard to health issues, lest the very traditional basis of our society thus be undermined in its basic underpinnings---and this bias is clearly reflected in clinical medicine with relation to Celiac disease. The preference is always, in "acknowledging anything"--to rather conclude some kind of mental health problem, which serves numerous purposes, not the least of which is to minimize the medical aspects lest medical doctors have to accept as much responsibility for caring for such patients as Dr. Lewey has graciously dared to do in his professional life here. The doctors I saw with my disease were in Northern Colorado and over a span of four years' time during the middle 1980's--I did not get done to "The Springs" until I went there to see a woman Naturopath named Shields, who while evidently quite learned generally, also held out zero practical help with my experience of severe Celiac Sprue that took me down to a weight of 119 pounds at age 30 standing six feet two inches in height.

    So I feel I have reason to remain upset over the ignorance of the past, and indeed, while ignorance is not confined to relatively rural areas of the country like Colorado, I certainly encountered a whole bunch in that state vis-a-vis this Celiac thing. And so I commend Dr. Lewey for his "new breed" attitude, a refreshing and necessary element in improving the quality of care of that percentage of us in society he may in fact encounter in his practice.

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    Guest John Wilson

    Posted

    I actually just got my testing done, and they tested for and provide results for the beta and alpha subunits.Thank you for all of the information though, it was great.

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    Guest Miško

    Posted

    On the verge of desperation, after a lifetime of misery (I am 52) and a feces sample on helicobacter pylori which tested negative. I have a very pronounced suspicion for celiac disease. This even before I have discussed this with my physician, which I certainly shall. Thanks, Adi and Sharon Mackey, your contributions are valuable for me.

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    Thank you for this article. It confirms suspicions that I had about family members in my family who probably have the disease and refuse to consider it. All members that I'm referring to have diabetes.

    I believe that my mother, who died of diabetes, probably had celiac disease. No one that I know of in my family had it, but then, where did I get it?? My daughter tested negative but we know she has it. She is OK as long as she avoids gluten.

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    My 3 yr old just had the genetic tests done - and those results, according to the doctor, not only diagnosed my son but helped treat my daughter (7 yrs old)

    My daughter (7) was finally diagnosed with Celiac earlier this spring, after years of tummy issues dating back before she could walk. Her case is so severe, that 10 months on the strict diet haven't cleared up her diarrhea or tummy cramps.

    My son (3) has been "failure to thrive" since before he could walk, but tested negative against Celiac this spring.

    He finally started gaining weight when we began our gluten-free quest for my daughter. After 10 months of the gluten-free diet for him, he's finally at the 50% for his age/weight/stature.... I didn't think I'd ever see that number again.

    Our doctor ran the genetic test on my son & his results were the double DQ2 - the highest risk factor for Celiac, associated with the most severe symptoms.

    He firmly declared my son officially "Celaic" based on history of failure to thrive & then growing exponentially on the diet, paired with his genetic results.

    He also said this genetic pairing of double DQ2 is dominant, and is certain my daughter is the same way. We are bypassing several passive tests on her, and going straight for immunosuppressive therapy. We finally have a confident doctor, and finally have answers.

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    Guest Melinda Landon

    Posted

    Thank you for this very informative article.

    I am a self diagnosed Coeliac…

    I had all the “classic†symptoms but was misdiagnosed by all the doctors that I've seen over a 13 year period!

    I have a sister that was properly diagnosed as Coeliac at 9 months old. At 15 years old, I had severe Anemia that didn't respond to any treatment, Fatigue, Nausea, terrible abdominal pains, weight gain etc but the doctors convinced me (and not my mum…) that I didn't have Coeliac based on a negative blood test and endoscopy.

    Finally, at 28, when the stomach pain attacks grew too close together I insisted on another blood test- which came out positive

    On the advice of my GP, I skipped the biopsy and started a gluten-free diet straight away. I had immediate positive affect on my overall health

    Since then, my 2 kids have been genetically tested. As they carry 1 gene only, the official result was “Coeliac disease cannot be ruled outâ€

    I chose to put them on a strict gluten-free diet, based on my experience. I just had a 3rd child and not even going to bother testing this time….

    My concern is regarding the effect of the 13 year long exposure to Gluten on the risk of bowl cancer

    If anyone could point me to some information regarding that I would appreciate it

    Hi, celiac myself and wanting to make a difference in the world by helping others. I would like to know if you are interested in sharing your story. You say touch the life of another going threw the same thing. I am writing a book of people wrongly diagnosed. Could you help me please. I would love to share your story.

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    I would hate to add up all the hundreds of dollars I have wasted trying to get healthy.  Now, however, I get healthy by focusing on one thing:  making my intestines healthy.  If my intestines are healthy, I can absorb food.  If I can absorb food, my body will be receiving the nutrition it needs to function, and thus I will be healthy.
    Of course, rule number one for all of us is to stay gluten free.  But, focusing on avoidance alone, can get depressing.  Instead, I like to focus on what I can do to strengthen my digestive system.  That way, all the good gluten free food I am consuming can actually benefit my body.  What good is eating healthy if you are unable to absorb the nutrients?  Pouring healthy food into a compromised gut would be as wasteful as pouring dollar bills over an ATM machine and hoping in vain to strengthen your bank account balance.
    Research shows that those of us with celiac disease/gluten intolerance often have decreased absorption despite following a strict gluten free diet.  Scott Adams summarized one of these articles on the celiac.com website back in 2003.  The article by Lee SK, et al. entitled “Duodenal Histology in Patients with Celiac Disease after Treatment with a Gluten-free Diet” implied that even though patients may feel better on a gluten-free diet, there may still be damaged intestinal areas that are incapable of optimal nutrient absorption.  Since specific nutrients are absorbed along specific locations in the small intestine, this can have long-term ramifications.  For instance, the proximal portion of the intestine is the site for absorption of vitamin B6 (pyroxidine).  If that portion is damaged, there will be decreased absorption, and your body will be deficient in B6.  You may then experience a range of neurological symptoms such as nervousness, irritability, and shakiness.  And, as happened in my case, you may see a doctor, only to be told you are having anxiety attacks and be handed a prescription for a mild tranquilizer.  Thankfully, I discovered that a good B6 supplement (Solgar “Magnesium with B6”) was all I needed and threw away the offending prescription, but this serves as an excellent—albeit oversimplified—example as to why we have to focus on improving the health of our intestines.
    Before I go on, I do want to say that the products listed below do not benefit me financially in the least.  Additionally, these are the products that work best for my body.  You may find a different brand works better for you, but as long as our focus is on getting those intestines healthy, we are all heading in the right direction!
    So, read on about what I personally consider the top four intestinal healing supplements…
    The first and best all-round product I have found that truly aids in restoring the intestinal lining is a glutamine supplement put out by a company called Metagenics.  The supplement, called “Glutagenics”, contains glutamine, licorice root, and aloe vera.  While studying for my masters in nutrition at Texas A&M University, we learned that glutamine is a key amino acid that aids in restoring the intestinal lining in patients that are transitioning from being tube-fed to a normal diet.   So, when my own chiropractor suggested this supplement and mentioned it contained glutamine, I purchased it and have been taking it on and off for three years.  
    Glutagenics is available online through various websites that carry the Metagenics brand. The supplement is unfortunately a bit cost prohibitive, but you can shop around for other brands that contain a similar blend, or buy the three active ingredients separately. Unfortunately, this did not work for me (I have an expensive gut), but it may for you.
    The next product is a good omega-3 fatty acid. Omega-3 fatty acids have so many benefits that even if you weren’t working on building up your intestines, they would still be beneficial. During my graduate research, I was fortunate to be part of an ongoing study on the mechanism whereby omega-3 fatty acids reduce the inflammatory response. Obviously, when our intestines are damaged, there is plenty of inflammation. So, including omega-3 fatty acids in our diet is vital.
    Thankfully, omega-3 fatty acids are getting easier and easier to come by. My family eats the high omega-3 brand eggs and the Smart Balance peanut butter and butter spreads. You can also purchase wonderful oil blends by Nordic Naturals. My favorite is the lemon-flavored Omega-3 liquid. The lemon flavor truly masks the fishy taste and even my children swallow the oil with minimal grumbling. Nordic Naturals is quite expensive (around $20.00 for 8 oz) but if you compare the amount of DHA you are getting per serving, it is definitely the most DHA for your dollar!
    Another great healing nutrient is zinc. Zinc is wonderful for wound healing- you’ll see it in many topical creams, but it also helps restore the intestines. Metagenics puts out a great supplement and their products are great for sensitive individuals. I find that 10mg works best for me. I don’t take it every day – too much will give you a bad taste in your mouth. Once I get that bad taste, I know I need to go off it for awhile.
    Finally (for now), find a great probiotic. The one that everyone recommends, by Garden of Life, contains wheat grass, so we have to avoid it. I do extremely well, however, on a product called Lacidophil by Xymogen. My energy levels actually improve on this brand. Xymogen has their own website where you can purchase products directly. Taking a good probiotic restores a healthy balance to your gut flora, which aids in overall health and digestion. I have just recently ordered one from Emerson Ecologics through a natural doctor and it’s supposed to be even better. It has many more strains of the good bacteria so I’m going to try it as soon as it comes in.
    Of the four products listed above, the two that I take daily are the probiotic and omega-3 oil. The other two I take on an ‘as-I-need-it’ basis.
    Unfortunately, our bodies don’t tolerate a lot of extra supplements, so go slowly and only add one at a time. Keep track of how you feel. You may never tolerate the mass quantities that some companies will try to sell you. But, since you are your own best manager, work with yourself slowly and patiently and you will find your health improves over time.
    May God bless you with the wisdom and discernment you need to live a healthy and vibrant life!


  • Recent Articles

    Alexander R. Shikhman, MD, PhD, FACR
    The Connection between Gluten Intolerance and Sjogren’s Syndrome
    Celiac.com 08/17/2018 - Mucosal dryness is among the top non-gastrointestinal complaints of patients with gluten intolerance and celiac disease.
    Prolonged eye dryness, itching and chronic inflammation of the eye lids (blepharitis), mouth dryness, excessive thirst, frequent yeast infections, skin dryness and vaginal dryness in women may represent clinical symptoms of Sjogren’s syndrome. Named after Swedish ophthalmologist Henrik Sjögren, Sjogren’s syndrome is one the most common (and one of the most commonly underdiagnosed) rheumatic/autoimmune diseases. The disease most frequently affects women (10 women for every man) and usually appears in women around and after menopause. However, the disease can affect either gender at any age.
    In addition to mucosal and skin dryness, Sjogren’s syndrome can cause joint pain and stiffness, damage to peripheral nerves leading to numbness and tingling of fingers and toes, fatigue, brain fog, inflammation of blood vessels, hair loss, poor food digestion due to pancreatic damage and various problems with the cardiac muscle and its conduction system causing arrythmia and myocarditis. Patients suffering from Sjogren’s syndrome quite frequently deal with recurring yeast infections, chronic periodontal disease, recurring canker sores and poor dental health.
    The diagnosis of Sjogren’s syndrome is based on:
    Demonstration of mucosal dryness upon physical examination Specific blood tests (positive anti-SSA/Ro and anti-SSB/La antibodies, elevated levels of serum immunoglobulin G) Ultrasound imaging of salivary glands On rare occasions, a diagnosis of Sjogren’s syndrome requires confirmation through a small salivary gland biopsy or special nuclear medicine studies.
    It is well documented that patients with gluten intolerance and celiac disease have an increased risk of Sjogren’s syndrome. Similarly, patients with Sjogren’s syndrome are characterized by the increased prevalence of gluten intolerance and celiac disease.
    The connection between Sjogren’s syndrome and gluten intolerance is not a coincidental one: there are well-studied molecular mechanisms explaining this link. In the late 1980s/early 1990s genetic studies in Sjogren’s patients demonstrated an increased presence of the class II major histocompatibility complex protein HLA DQ2. Furthermore, HLA DQ2 positivity was found to be associated with increased titers of Sjogren’s specific anti-SSA/Ro and anti-SSB/La antibodies. The link between gluten and Sjogren’s syndrome became obvious in the mid to late 1990s when it was discovered that HLA-DQ2 binds to deamidated gluten peptides and presents them to mucosal CD4+ T cells thus initiating a chain of events eventually leading to autoimmune responses.
    The second set of data came from the discovery of BM180 protein. This protein regulates tear secretion in the lacrimal acinar cells. Suprisingly, amino acid sequence of BM180 has a similarity with alpha-gliadin and, therefore, can attract inflammatory cells activated by gluten thus contributing to the development of eye dryness.
    The actual prevalence of gluten intolerance in Sjogren’s patients based on published data varies from 20% to 40% depending on the criteria used to define gluten intolerance. The data from our clinic (Institute for Specialized Medicine) indicate that gluten intolerance can affect almost half of patients with Sjogren’s syndrome. Additionally, our data show that one third of patients with gluten intolerance have evidence of mucosal dryness and Sjogren’s syndrome.
    The frequency of documented celiac disease in patients with Sjogren’s syndrome is in the vicinity of 5%.
    The following is a patient case history from our clinic:
    A 28 year old woman was seen in our clinic due to her complaints of long-standing irritable bowel syndrome and recent onset of eye dryness. Her initial presentation included abdominal pain, bloating and irregular bowel movements. She was seen by several gastroenterologists and underwent several upper endoscopies and colonoscopies with mucosal biopsies which were non-diagnostic. Her lab test results showed positive IgG anti-gliadin antibodies and she was told that “this is a common finding among healthy people, and is not indicative of any illnesses.” She was seen by her ophthalmologist and prescribed with contact lenses which she could not wear due to significant eye discomfort and irritation. Further eye examination showed that she had diminished tear production and was referred to our clinic to rule out Sjogren’s syndrome. Upon physical examination in our clinic the patient not only demonstrated profound eye dryness but also showed evidence of dry mouth, fissured tongue and patchy areas of thrush as well as very dry skin. A sonographic evaluation of her major salivary glands was suspicious for moderately advanced Sjogren’s syndrome. Her laboratory test results showed: positive anti-SSA/Ro antibodies, elevated serum immunoglobulin G, low neutrophil count as well as low levels of vitamin D and ferritin (a serum marker of iron storage state). Also, the patient was found to have positive serum IgG and salivary IgA anti-gliadin antibodies as well as positive HLA DQ2 (a molecular marker associated with gluten intolerance).
    Based on a combination of clinical history, physical findings and laboratory test results, the patient was diagnosed with gluten intolerance and Sjogren’s syndrome. In addition to the aforementioned tests, the patient underwent food intolerance testing based on serum IgG4 antibodies which showed not only gluten but also cow’s casein intolerance. Her treatment options included a traditional route of therapy based on drugs or an integrative approach based on dietary modifications and food supplements. She opted for the integrative approach and started a gluten-free and dairy-free diet as well as iron glycinate, vitamin D, specific probiotics and digestive enzymes.
    After the first month on the diet and supplements, she reported a remarkable improvement of her irritable bowel symptoms and in three months, she started noticing an improvement of the dryness. Laboratory tests performed six months after initiation of the therapy showed normalization of the IgG level, disappearance of anti-SSA/Ro antibodies and a slightly suppressed neutrophil count. Through following the prescribed diet and supplements she is now symptom free.
    Why do we need to treat Sjogren’s syndrome? Left untreated, Sjogren’s syndrome can cause debilitating dryness affecting gastrointestinal and respiratory tracts. Clinically, this manifests as difficulty in swallowing solid foods, heartburn, malabsorption of nutrients and minerals, bloating, weight loss, chronic sinus infections and prolonged dry cough. Sjogren’s syndrome also significantly increases the risk for malignancies affecting lymphatic nodules, known as lymphomas.
    Therapy for Sjogren’s syndrome is based on the treatment of mucosal dryness and the autoimmune component of the disease. In addition, patients affected by Sjogren’s syndrome need to have regular screenings for malignancies (specifically lymphomas) and premalignant conditions.
    Traditional therapy for Sjogren’s syndrome (treatment of dryness):
    Cyclosporin (brand name Restasis) eye drops and artificial tears for dry eyes. Numoisyn lozenges and liquid, as well as Caphosol for mouth dryness and mucositis. Cevimeline (brand name Evoxac) and pilocarpine (brand name Salagen) for systemic dryness therapy. Treatment of autoimmune disturbances:
    Hydroxychloroquin (brand name Plaquenil). Leflunomide (brand name Arava). Severe autoimmune conditions associated with Sjogren’s syndrome are treated with the biologic drug rituximab (brand name Rituxan). Integrative therapy for Sjogren’s syndrome. Ear acupuncture (auricular therapy) and body acupuncture to stimulate tear and saliva production. Elimination diet based on individual food-intolerance profiles. Oral probiotics (for example, BLIS K12) and intestinal probiotics. Digestive enzymes. Fish and krill oils. Black currant seed oil. Cordyceps sinensis in combination with wormwood extract to treat the autoimmune component of Sjogren’s syndrome. Zinc and elderberry lozenges. N-acetyl-L-cysteine and glutathione. Our extensive clinical experience demonstrate that early cases of Sjogren’s syndrome can be completely reversed (by both clinical and laboratory criteria) by the strict gluten-free and elimination diet. The advanced cases cannot be reversed; however, even in advanced cases the gluten-free and elimination diet can slow the progression of the disease.
    If you’re concerned that dryness may represent Sjogren’s syndrome, see a rheumatologist for further evaluation and management of your condition.
    References:
    Alvarez-Celorio MD, Angeles-Angeles A, Kraus A. Primary Sjögren’s Syndrome and Celiac Disease: Causal Association or Serendipity? J Clin Rheumatol. 2000 Aug;6(4):194-7. Asrani AC, Lumsden AJ, Kumar R, Laurie GW. Gene cloning of BM180, a lacrimal gland enriched basement membrane protein with a role in stimulated secretion. Adv Exp Med Biol. 1998;438:49-54. Feuerstein J. Reversal of premature ovarian failure in a patient with Sjögren syndrome using an elimination diet protocol. J Altern Complement Med. 2010 Jul;16(7):807-9. Iltanen S, Collin P, Korpela M, Holm K, Partanen J, Polvi A, Mäki M. Celiac disease and markers of celiac disease latency in patients with primary Sjögren’s syndrome. Am J Gastroenterol. 1999 Apr;94(4):1042-6. Lemon S, Imbesi S., Shikhman A.R. Salivary gland imaging in Sjogren’s syndrome. Future Rheumatology, 2007 2(1):83-92. Roblin X, Helluwaert F, Bonaz B. Celiac disease must be evaluated in patients with Sjögren syndrome. Arch Intern Med. 2004 Nov 22;164(21):2387. Teppo AM, Maury CP. Antibodies to gliadin, gluten and reticulin glycoprotein in rheumatic diseases: elevated levels in Sjögren’s syndrome. Clin Exp Immunol. 1984 Jul;57(1):73-8.

    Jefferson Adams
    Can a Gluten-Free Diet Normalize Vitamin D Levels for Celiac Patients?
    Celiac.com 08/16/2018 - What is the significance of vitamin D serum levels in adult celiac patients? A pair of researchers recently set out to assess the value and significance of 25(OH) and 1,25(OH) vitamin D serum levels in adult celiac patients through a comprehensive review of medical literature.
    Researchers included F Zingone and C Ciacci are affiliated with the Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; and the Celiac Center, AOU San Giovanni di Dio e Ruggi di Aragona, University of Salerno, Department of Medicine and Surgery, Salerno, Italy. 
    Within the wide spectrum of symptoms and alteration of systems that characterizes celiac disease, several studies indicate a low-level of vitamin D, therefore recent guidelines suggest its evaluation at the time of diagnosis. This review examines the data from existing studies in which vitamin D has been assessed in celiac patients. 
    Our review indicates that most of the studies on vitamin D in adult celiac disease report a 25 (OH) vitamin D deficiency at diagnosis that disappears when the patient goes on a gluten-free diet, independently of any supplementation. Instead, the researchers found that levels of calcitriol, the active 1,25 (OH) form of vitamin D, fell within the normal range at the time of celiac diagnosis. 
    Basically, their study strongly suggests that people with celiac disease can recover normal vitamin D levels through a gluten-free diet, without requiring any supplementation.
    Source:
    Dig Liver Dis. 2018 Aug;50(8):757-760. doi: 10.1016/j.dld.2018.04.005. Epub 2018 Apr 13.  

    Jefferson Adams
    Could Gluten-Free Food Be Hurting Your Dog?
    Celiac.com 08/15/2018 - Grain-free food has been linked to heart disease in dogs. A canine cardiovascular disease that has historically been seen in just a few breeds is becoming more common in other breeds, and one possible culprit is grain-free dog food. 
    The disease in question is called canine dilated cardiomyopathy (DCM), and often results in congestive heart failure. DCM is historically common in large dogs such as Great Danes, Newfoundlands, Irish Wolfhounds, Saint Bernards and Doberman Pinschers, though it is also affects some Cocker Spaniels.  Numerous cases of DCM have been reported in smaller dogs, whose primary source of nutrition was food containing peas, lentils, other legume seeds or potatoes as main ingredients. These reported atypical DCM cases included Golden and Labrador Retrievers, a Whippet, a Shih Tzu, a Bulldog and Miniature Schnauzers, as well as mixed breeds. 
    As a result, the U.S. Food and Drug Administration's Center for Veterinary Medicine, along with a group of veterinary diagnostic laboratories, is investigating the possible link between DCM and pet foods containing seeds or potatoes as main ingredients. The good news is that in cases where the dog suffers no genetic component, and the disease is caught early, simple veterinary treatment and dietary change may improve heart function.
    According to Nutritional Outlook, an industry publication for makers of dietary supplements and healthy foods and beverages, there is a growing market for “free from” foods for dogs, especially gluten-free and grain-free formulations. In 2017, about one in five dog foods launched was gluten-free. So, do dogs really need to eat grain-free or gluten-free food? Probably not, according to PetMD, which notes that many pet owners are simply projecting their own food biases when choosing dog food.
    Genetically, dogs are well adapted to easily digest grains and other carbohydrates. Also, beef and dairy remain the most common allergens for dogs, so even dogs with allergies are unlikely to need to need grain-free food. 
    So, the take away here seems to be that most dogs don’t need grain-free or gluten-free food, and that it might actually be bad for the dog, not good, as the owner might imagine.
    Stay tuned for more on the FDA’s investigation and any findings they make.
    Read more at Bizjournals.com
     

    Jefferson Adams
    Did You Miss the Gluten-Free Fireworks This Past Fourth of July?
    Celiac.com 08/14/2018 - Occasionally, Celiac.com learns of an amusing gluten-free story after the fact. Such is the case of the “Gluten-Free Fireworks.” 
    We recently learned about a funny little event that happened leading up to Fourth of July celebrations in the town of Springdale in Northwest Arkansas. It seems that a sign advertising "Gluten Free Fireworks" popped up near a fireworks stand on interstate 49 in Springdale. 
    In case you missed the recent dose of Fourth of July humor, in an effort to attract customers and provide a bit of holiday levity, Pinnacle Fireworks put up a sign advertising "gluten-free fireworks.” 
    The small company is owned by Adam Keeley and his father. "A lot of the people that come in want to crack a joke right along with you," Keeley said. "Every now and then, you will get someone that comes in and says so fireworks are supposed to be gluten-free right? Have I been buying fireworks that have gluten? So then I say no, no they are gluten-free. It's just a little fun."
    Keeley said that their stand saw a steady flow of customers in the week leading up to the Fourth. In addition to selling “gluten-free” fireworks, each fireworks package sold by Pinnacle features a QR code. The code can be scanned with a smartphone. The link leads to a video showing what the fireworks look like.
    We at Celiac.com hope you and your family had a safe, enjoyable, and, yes, gluten-free Fourth of July. Stay tuned for more on gluten-free fireworks and other zany, tongue-in-cheek stories.
    Read more at kark.com
     

    Jefferson Adams
    Stress-Related Disorders Associated with Higher Risk for Autoimmune Disease
    Celiac.com 08/13/2018 - It’s not uncommon for people to have psychiatric reactions to stressful life events, and these reactions may trigger some immune dysfunction. Researchers don’t yet know whether such reactions increase overall risk of autoimmune disease.
    Are psychiatric reactions induced by trauma or other life stressors associated with subsequent risk of autoimmune disease? Are stress-related disorders significantly associated with risk of subsequent autoimmune disease?
    A team of researchers recently set out to determine whether there is an association between stress-related disorders and subsequent autoimmune disease. The research team included Huan Song, MD, PhD; Fang Fang, MD, PhD; Gunnar Tomasson, MD, PhD; Filip K. Arnberg, PhD; David Mataix-Cols, PhD; Lorena Fernández de la Cruz, PhD; Catarina Almqvist, MD, PhD; Katja Fall, MD, PhD; Unnur A. Valdimarsdóttir, PhD.
    They are variously affiliated with the Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; the Department of Epidemiology and Biostatistics, Faculty of Medicine, University of Iceland, Reykjavík, Iceland; the Department of Rheumatology, University Hospital, Reykjavík, Iceland; the Centre for Rheumatology Research, University Hospital, Reykjavík, Iceland; the National Centre for Disaster Psychiatry, Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden; the Stress Research Institute, Stockholm University, Stockholm, Sweden; the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; the Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden; the Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden; the Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; and the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
    The team conducted a Swedish register-based retrospective cohort study that included 106, 464 patients with stress-related disorders, 1,064 ,640 matched unexposed individuals, and 126 ,652 full siblings to determine whether a clinical diagnosis of stress-related disorders was significantly associated with an increased risk of autoimmune disease.
    The team identified stress-related disorder and autoimmune diseases using the National Patient Register. They used Cox model to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors.
    The data showed that being diagnosed with a stress-related disorder, such as post-traumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions, was significantly associated with an increased risk of autoimmune disease, compared with matched unexposed individuals. The team is calling for further studies to better understand the associations and the underlying factors.
    Source:
    JAMA. 2018;319(23):2388-2400. doi:10.1001/jama.2018.7028