• Join our community!

    Do you have questions about celiac disease or the gluten-free diet?

  • Ads by Google:
     




    Get email alerts Subscribe to Celiac.com's FREE weekly eNewsletter

    Ads by Google:



       Get email alertsSubscribe to Celiac.com's FREE weekly eNewsletter

  • Member Statistics

    77,483
    Total Members
    3,093
    Most Online
    jmurdesh
    Newest Member
    jmurdesh
    Joined
  • 0

    The Story of the Origin of EnteroLab: 15 years Later 2000-2015


    Kenneth Fine, MD


    • Journal of Gluten Sensitivity Winter 2015 Issue


    Image Caption: Image: CC--Idaho National Laboratory

    Celiac.com 06/20/2016 - One evening in October 1999, while in my academic office at Baylor University Medical Center, Dallas, my professional and personal life changed in an instant. I had recently had the idea of testing stool for gluten sensitivity to possibly prove that patients with microscopic colitis, whom displayed an epidemiologic, pathologic, and genetic overlap with celiac disease but who rarely had positive blood tests against gluten (because they rarely had the small bowel villous atrophy of celiac disease; they had colitis which is inflammation in the colon). I had remembered that previous researchers in Scotland invasively placing tubes into certain patients without villous atrophy had been able to find antibodies to gluten deep inside the small intestine when they were absent from the blood. They called these patients latent celiacs. However, they never reported results of testing stool, which would have been a lot easier to collect because it did not require the multiple hours and patient invasion of placing tubes deep inside the intestine.


    Ads by Google:




    ARTICLE CONTINUES BELOW ADS
    Ads by Google:



    That October afternoon I received the first set of results from my laboratory of a newly improved method we had developed for testing stool for the presence of antigliadin IgA, the main antibody against wheat gluten. It was about 7:00PM, it was dark outside, and late enough in the office for everyone to have gone home, allowing me a quiet setting to review these results. What I saw that night seemed like a window into the future and a medical-scientific Pandora's box, all at the same time. Not only did I see that about 75% of the microscopic colitis patients had a positive fecal antigliadin test but 25% of asymptomatic volunteers did also. I quickly did the math, and realized that celiac disease at a prevalence of even 1% would pale in comparison to these statistics, revealing that hundreds of thousands of people in the US and the world may be gluten sensitive without having celiac disease. I knew that I had just been given information that no one else in the world knew, and that it would likely have major public health implications resulting from a new dietary-induced disease paradigm. That the main staple food of Western civilization may be causing large percentages of the population to have symptoms and syndromes, not only colitis, but perhaps also irritable bowel syndrome, autoimmune syndromes, short stature in children, multiple allergies and chemical sensitivities, and even idiopathic psycho-neurologic syndromes like depression, Parkinson's Disease or Lou Gehrig's disease. Not to mention what it might mean for me as the holder of this information.

    Then it happened—the most significant moment of my life up to that point—it felt like someone had tapped me on my left shoulder. Though I knew I was alone in the office, I turned to the left and looked upward for some reason for what or whom might have tapped me on my shoulder. And though, while I saw no one there, I immediately knew there was a presence with me at that moment, a spiritual or angelic presence. And then I heard these words in my head "You have to leave this place". And within minutes, the decision came to me that I indeed did have to leave my academic post of 15 years to bring the results of this new fecal testing method to the public: to the 25% of otherwise asymptomatic people reacting to dietary gluten with the same immunologic reaction measured in celiac disease, antigliadin antibody, as well as to the 75% of patients with microscopic colitis and perhaps other GI ailments and syndromes who, with a gluten-free diet, might heal their chronic refractory inflammatory bowel conditions.

    This was a bold line of thinking for me, as I had been on a professional trajectory toward the normal milestones of a successful young academic medicine career, becoming head of a sub-specialty medical department (for me, Gastroenterology), the prospects for which had just begun to surface in my life. Yet, I had just been called it seemed, by an encounter with a supernatural force, to an assignment of sorts with a mission to fulfill. And so, the idea of creating a specialty intestinal laboratory to make this new line of testing available to those in need of its benefits was born, EnteroLab.com (entero means intestine in Greek and in medical terminology). A "dot com" I thought? Yes, this form of testing should originate "in the comfort of your own home". Why make people with GI problems fly on an airplane half way across the country merely to give stool specimens for lab analysis (the practice of my Dallas hospital for decades up until that time). If I could create a mechanism whereby only the specimens but not the person could do the flying, then we could deliver results and follow-up dietary recommendations electronically, and the healing would begin shortly thereafter with dietary elimination of the causative antigenic foods. And if the client desired, they could have a paid phone consult with me or my nurse and still not have to spend the time, money, and difficulty flying to Dallas. And I have to admit, in 2000 it was kind of exciting to be the first doctor in the world to turn his entire medical career over to the internet, as well as to have created the first clinical laboratory serving people directly without the need of a prescription or previous doctor's visit, both incredibly bold and revolutionary ideas at the time (and perhaps still).

    I had learned from similar major paradigm shifts in my field of gastroenterology (specifically, in 1983 when doctors in Australia found in their research that ulcers might be caused by bacteria, but whom were laughed at and ignored for about 15 years, yet later in 2005 received a Nobel prize) that it would likely take 15-20 years before anyone in the medical field would believe my new research findings relating to non-celiac gluten sensitivity and its simple diagnosis with fecal testing. This, even though I was regarded even at my young age as an expert in the field, with a significant track record for developing unique and successful ideas for diagnosis and treatment of GI diseases (see my CV at www.intestinalhealth.org/CV), and having been trained by one of the most successful and respected gastroenterologists of all time, Dr. John Fordtran. While my medical peers might not believe my results for some time, people suffering the symptoms would not care whether or not it was too soon for a scientific paradigm to shift, because they would want to try a gluten-free diet to get better. And try, they did. Following positive stool test results from EnteroLab, they got better in droves going gluten-free, and in most cases with complete healing of long-standing symptoms and syndromes. And eventually I predicted, with such remarkable improvements that had never been possible before, their health practitioners (at least the honest, inquisitive, and non-egotistical ones) would ask them what had brought on such improvement. Eventually these practitioners would begin sending other patients for the same testing that had opened the door to the dietary miracle the gluten-free diet posed for those previously tested.

    Beyond the consequences of having to leave my academic positions and stature behind, I had to withstand some public and more often professional criticism for undertaking a bold and somewhat maverick professional move without the permission of my peers in doing so. This does not always go over smoothly in scientific and medical professional circles. Despite having been a highly respected young published researcher at that time (40 publications by the time I was in my mid-30's), my submissions both to professional GI society meetings and GI journals (journals that I had served as a reviewer for years) were rejecting my research submissions relating to this new paradigm of non-celiac gluten sensitivity. And it seemed, the rejections were not for objective reasons, but more subjective and for principle. Other researchers in this specific field and other fields have had to endure similar treatment. Sadly, submissions to these journals addressing paradigm-shifting topics are not always reviewed in unbiased, objective ways if they deal with a subject or contain conclusions that go against what the reviewers inherently believe to be true at that time (the "I'll see it when I believe it" scenario rather than "I'll believe it when I see it"). And yet, despite submissions of excellently performed and written studies that were rejected for these reasons by a system that seemed unready for this new paradigm, the most common public and professional criticisms of my methods primarily centered around my "lack of publication". This seemed circular and nonsensical to me. After all, had Michael Dell ever published his methods of making computers delivered in a revolutionary way (mail order) to its customers? These computers worked and served its customers well without a published method? Why is lack of publication of a medical technologic method equated with lack of Truth or efficacy? My response was and still is to remain true to my own data and experience, and my desire to serve and help people, and to not proceed according to the needs and critical dictates of others having no experience with my techniques.

    And so, 15 years later, as EnteroLab approaches our millionth patient tested, and with the current number of referring health practitioners in excess of 1,500, EnteroLab.com stands as a successful purveyor of medical Truth and public service. I ask people "How could hundreds of thousands of people be satisfactorily served over 15 years if what we are doing was not worthy and True?"; at some point, a person's or business' track record has got to stand for something positive and meaningful. And it seems my estimate of the time it would take for other researchers or mainstream practitioners to begin getting on board with the new paradigm was correct. Non-celiac gluten sensitivity has recently been further researched and substantiated to exist, just as I reported in public and professional lectures as early as 1999 (but published by others as early as 1980). And it has only been in the last 2 years or so that I have seen the question being raised at national and international GI meetings by "celiac researchers", but at least they are now doing so. Yet, the public has been the patron of the paradigm all along. In the last 4-5 years gluten-free food companies have carried the ball farther down the field than ever before. Yet interestingly, this focus on the food has mistakenly led people to regard this serious clinical syndrome as "a diet" not a disorder. And as we all know, "diets" come and go for people, even week to week. This is not healthful for any diet, but especially not for a gluten-free diet where the immune system can be hyperstimulated by repeatedly withdrawing and reintroducing such an immunogenic food. And yet, whether or not people choose to test for the syndrome with our stool test (the only test available to sensitively detect non-celiac gluten sensitivity), if they decide to go gluten-free, that must be a lifelong dietary decision. Otherwise, the test should be employed to help determine how serious the circumstances might be, and to further reinforce the clinical need of its permanency. Because after all, 25% of people, even when asymptomatic, have detectable immune reactions to gluten, and in many of these, damage to the intestine can be detected as well (measurable by EnteroLab from a fecal fat test from the same stool specimen).

    We have stood firm on the Truth of our research and clinical results, patiently waiting these 15 years for the public and professional paradigm-thinking to catch up. And catch up it has. Everyone today has at least heard about gluten, and people are not called crazy because going gluten-free makes them better physically, mentally and/or emotionally. But our work is not done. There are many millions more children and adults suffering not only from gluten sensitivity, but from other food sensitivities as well, and other diet-related maladies (obesity, endocrine problems including diabetes, eating disorders, food addictions, etc.). I am appreciative of the support and respect given to me and EnteroLab by Celiac.com and its founder, Scott Adams, who also knew early on there was something real about gluten sensitivity. His 14 year old "Journal of Gluten Sensitivity" is evidence of that.

    And so now, we are proud to partner with Celiac.com by allowing them to be the first company outside our own to offer our proprietary EnteroLab tests for sale, having created some special gluten-oriented testing panels for them. And as we go into the next decades of service, I leave you with a hint of the next, new paradigm… which is really the old paradigm. Gluten sensitivity is not limited to wheat, barley, and rye, but often includes oats as well (not just because of wheat contamination of the oats). This was the clinical standard from its beginning by the founder of the gluten-free diet, Dr. Willem Dicke, but that got changed in the last 10-15 years by substandard research methods based only on celiac disease as the end point and bias toward wanting to find such a result (all studies contain bias by the researchers, it's the nature of the mind influencing reality). So for the first time anywhere, we are using a diagnostic test for non-celiac oat sensitivity, and showing that about 50% of people reacting to wheat, barley, and rye, also react to oats with a similar immunologic reaction detectable in stool. But more on this as the information and paradigm-acceptance develops. Hopefully, this one won't take another 15 years to be accepted.

    We at EnteroLab and my non-profit public educational institute, The Intestinal Health Institute (www.IntestinalHealth.org), have been greatly honored to serve all our patrons to date, and we look forward to meeting and serving more of you in the future. For more information on testing at EnteroLab.com, please call 972-686-6869 or go to www.EnteroLab.com. Thank you for reading this historic account.

    0


    User Feedback

    Recommended Comments

    Guest Kelly

    Posted

    Dr. Fine has done so much for all of us. I'm sure all who have been inspired and helped by him will say he changed their lives. Thank you Dr. Fine for fighting for us. We all truly appreciate what you have done for us.

    Share this comment


    Link to comment
    Share on other sites
    Guest Suzanne

    Posted

    Kelly expressed it well. Dr. Fine's testing saved the life of one of my friends and has helped many others. I recommend it to everyone I can. Thank you for being willing to think and practice outside of the box, Dr. Fine. You are a hero.

    Share this comment


    Link to comment
    Share on other sites
    Guest Roland Ludlam

    Posted

    Thank you, Dr. Fine, for your courage and conviction. I was diagnosed in 2007 through the stool test and the past 9 years have been the best of my whole adult life. Keep up the good work!

    Share this comment


    Link to comment
    Share on other sites

    Enterolab diagnosed my gluten, dairy and soy sensitivities in 2010, one year after my microscopic colitis diagnosis. Within weeks of changing my diet, I had my life back. I wish someone would let him publish his research. More people need access to this test, and insurance coverage for it!

    Share this comment


    Link to comment
    Share on other sites


    Your content will need to be approved by a moderator

    Guest
    You are commenting as a guest. If you have an account, please sign in.
    Add a comment...

    ×   Pasted as rich text.   Paste as plain text instead

      Only 75 emoji are allowed.

    ×   Your link has been automatically embedded.   Display as a link instead

    ×   Your previous content has been restored.   Clear editor

    ×   You cannot paste images directly. Upload or insert images from URL.


  • Popular Contributors

  • Ads by Google:

  • Who's Online   17 Members, 1 Anonymous, 394 Guests (See full list)

  • Related Articles

    Susan Costen Owens
    Celiac.com 07/17/2015 - This article originally appeared in the Spring 2015 edition of Journal of Gluten Sensitivity.
    Why is a researcher whose field for twenty years has been autism now writing an article about celiac disease and its possible relationship to oxalate? This takes a little explaining.
    My training in graduate school was all about looking into old literature to find pieces of research that had been lost, or were never incorporated into current models. I learned that new science could provide a different context for old findings. The importance of this process came home when more than a decade ago I was sitting at an enormous oval table at the National Institutes of Health where an important meeting was addressing how the heads of various National Institutes of Health and the CDC would handle a theory about a possible environmental trigger related to autism. One scientist rose to the floor, and began to explain his reason for discounting the new theory's importance. He proposed that this theory did not fit into previous models of autism, and began to say that the scientific process worked like the construction of a brick wall. Everything added to that wall should fit into the foundation and bricks that had already been laid.
    How often does this view of science as being a construction of human beings, rather than a discovery of nature, keep us from accepting new lines of research? Has scientific consensus ever ended up wrong after the appearance of new findings? Yes, many times.
    In this meeting at the NIH, at that moment, a senior scientist, Dr, Bernard Rimland, rose to the floor. Those who knew this man realized he had singularly changed the view about the science of autism twice, accomplishing these major shifts of thinking during different decades. I don't have a transcript from that meeting, but Dr. Rimland rose to say something like this: "My experience is very different. I find that science is more like a crossword puzzle, in that you may have been working at the puzzle from one end and filled in places that looked correct until you began working from another side and discovered that something you filled in before must have been wrong. That's when you erase the part that you thought had been right, and you find another answer that will make the parts fit from both directions."
    That speech has been a guiding light to my own research since then, helping me have the motivation to recover all the pieces that were lost or misunderstood or left out from the past whose absence left a model that only approximately provided a place for all the known pieces, but left many other pieces "loose" and unable find a proper fit.
    In 2005 after spending ten years studying the biological roles of sulfate in the body, I began to investigate another negatively charged ion that travels on the same transporters. I reviewed the published literature on oxalate in any condition, looking at basic science and clinical research over the last two centuries. I was looking for gaps and opportunities for improving the identification of oxalate-related diseases outside the kidney. My work for twenty years had focused most intensely on autism, and I had found that oxalate was high in autism, but this finding needed to be put in context and studied formally. It was mystifying to me why work from basic science about oxalate was only being applied to patients with kidney disease. How could we identify others with oxalate-related disorders?
    In the fall of 2005, along with several associates, we started our Oxalate Project. Using the same methodologies I had developed in the previous decade using the internet to interact with a broad range of patients, we began seeking those with any condition that was already related to oxalate in the literature, and patients with other conditions where the science took us. Included in this effort was setting up a project at the Autism Research Institute that we named the Autism Oxalate Project.
    In October of 2006, I attended the International Celiac Disease Symposium in New York City. I was hoping that the findings in oxalate research on malabsorption and intestinal disease, and specific findings on oxalate in celiac disease published since the 1970's were being discussed at this conference. I heard not a word about oxalate there. These scientists probably did not realize that when oxalate levels in the blood become high, it can get stored all over the body where it can produce effects in any potential organ…not just the kidney. I had learned that systemic effects from oxalate could change the course of a condition in patients over years of time. For patients with celiac disease, this storage might have occurred primarily during the years before diagnosis when problems with fat digestion would have increased the percent of oxalate absorption from the diet.
    In autism, I had learned that, as in celiac disease, some investigators had noticed oxalate's elevation in urine in isolated individuals, but they had been taught by articles in peer-reviewed literature to dismiss this finding as irrelevant when those individuals didn't have kidney stones. Basically, the literature kept saying that kidney stones would always be the first presentation of an oxalate problem—but was that true? Why would that be true? As I began to attend numerous world conferences on oxalate, I was very surprised to find that the only people there besides botanists, were those involved in kidney research. My previous studies in the literature had identified many articles describing oxalate producing effects all over the body and in multiple systems. New work on oxalate transport was finding regulation of oxalate's movement all over the body. Why wasn't this research being applied to patient care outside the kidney and why were certain laboratories insisting on a kidney diagnosis before they would even measure oxalate?
    Since my own work at that point included running a support group for people reducing oxalate and our doors were open for people with any condition, we had seen patients with more than twenty different conditions report an easing of their symptoms or even complete cures when they brought their oxalate levels down. Would the scientists be able to catch up with this wealth of experience that today has involved more than 17,000 families?
    Here is an example: I worked with a team of oxalate and autism researchers in Poland to establish the prevalence of oxalate's elevation in autism. The study that this work produced became available online in 2011, but officially went to print in September of 2012 in the European Journal of Paediatric Neurology. It was the first study to examine whether the levels of oxalate in blood plasma would correlate to the levels in 24 hour collections of urine in those who were not in kidney failure. We discovered that the levels in these two compartments did not correlate at all, especially in the controls. This meant that the oxalate field's dependence on urine tests as sufficient to identify those with oxalate problems was probably misplaced. It made sense that the two compartments would not "agree" because oxalate's movement between tissues, we now know, is regulated and its regulation would be different in different organ systems. How many other conditions were experiencing effects from elevated oxalate in blood that were not accurately reflected by only using urine tests? What did we know about variability from day to day, or even rhythms within the day, for oxalate secretion in other conditions? What did we know about how any variability should affect the interpretation of lab results, or our interpretation about the timing and presentation of symptoms in other conditions?
    A striking finding in our paper seemed to have been also referenced in a paper from Mayo Clinic, showing that urine oxalate in normal controls seemed to stay below the reference level of 0.46 mmol/1.73 m2 (24 hr.) Perhaps the point of the kidneys regulating that level so tightly was to protect the kidneys from risks of kidney stones or nephrocalcinosis, but that particular control of urinary secretion seemed lacking in autism. Scientists were beginning to discover secretion to other compartments, such as the intestines, the lungs, and the skin for example. Why would someone doing research even think to measure oxalate secretion and regulation in these other sites in clinical settings? In the past, everyone had assumed that measuring urine was sufficient. The graph of plasma versus urine looked completely different in those with autism compared to controls. What would a similar graph look like in celiac disease? Would the graph show different patterns at different ages, or before and after treatment with a gluten-free diet? Data from a study from Saccomani et al. may suggest that a limit to urinary secretion may be preserved in children with celiac disease, but would limiting secretion in the kidney sometimes lead to a greater accumulation of oxalate in tissues?
    Our autism study revealed that there are problems with assuming that a single urine test could be used to screen patients when oxalate could be elevated in blood and causing problems in the rest of the body. More than fifteen years ago (not published but presented at a think tank) I noticed problems in lab tests in autism with what looked like it could be caused by a variability in creatinine secretion. This would create a problem in interpretation for any urine test ratioed to creatinine, but the reason we would see this variability in autism made sense when a rat study recently found that oxalate in the kidney changes the movement of creatinine out of blood and into urine when oxalate was made to be high experimentally. This type of study urgently needs to be replicated in humans before anyone can have confidence that this affect on creatinine isn't compromising our data from spot urine tests. Suddenly it seems very sensible that in the oxalate field, it has become common practice to use 24 hour tests. Readers need to realize that this issue would affect anything measured in urine and ratioed to creatinine, not just oxalate! From data I've reviewed and analyzed statistically from more than a thousand organic acid tests, and from other literature, I also doubt that this single mechanism is solitary in contributing to problems in interpreting urine tests that use this ratio.
    Can we still legitimately think that physicians should not worry about oxalate levels unless their patients have developed kidney stones? Celiac disease is one of many conditions where high oxalate levels have frequently been found in patients. Some of the other conditions include bariatric surgery, cystic fibrosis, inflammatory bowel disease, short bowel syndrome, autism and more.
    Are doctors and nutritionists understanding that patients with these disorders will experience risks from oxalate to the rest of their body? Are they noticing when these patients develop issues outside the kidney that their symptoms might be related to oxalate? I've learned that the answers to these questions is most often, no.
    In our project's work with such patients we have reduced body oxalate levels through strategies of dietary modification, and by the use of specific vitamins, minerals and probiotics that have been shown to reduce oxalate. We've seen these changes alter the expression of their presenting disease in unforeseen but positive ways. It will take decades before all our findings from ten years of work in dozens of conditions can be confirmed by scientific studies. That does not mean these patients have to wait for academic studies to be published to see for themselves if reducing their exposure to this clearly recognized toxin will help improve their own health.
    Do physicians know that research on kidney stone patients have identified issues in their kidneys that lead to their increased risks of forming kidney stones from oxalate levels that would not produce stones in others? Could oxalate that was elevated in blood and tissues (and currently not being secreted at high levels in urine) cause problems to other parts of the body, contributing in unknown ways to comorbidities like those found in celiac disease?
    At the celiac symposium I attended, there were so many issues that were being discussed as being unresolved by the use of a gluten-free diet. That surprised me. Could those issues have been triggered by oxalate that was absorbed into the body before a gluten-free diet had resolved steatorrhea? Steatorrhea is the condition where excess fat stays in the feces, possibly causing the stool to float or have an oily appearance. Studies had shown that untreated celiac disease often was associated with steatorrhea. This condition elevates fat in the gut and that fat travels undigested all the way to the colon. Oxalate scientists had found that the fat left in the intestines during the journey to the colon would tie up calcium that ordinarily binds oxalate from the diet. About 80% of the calcium that travels through the gut stays in the gut. The purpose may involve the formation of a calcium oxalate salt in the feces that limits oxalate's absorption in the colon. Otherwise that oxalate could be transferred to blood if it is not first metabolized by the microbes in the gut. This is a bigger problem than the higher amount of oxalate in the diet. This might become a more serious problem when people with celiac disease use new grains that are gluten-free but which we know now are extremely high in oxalate.
    During the mid-nineteen thirties, prominent groups began recommending adding vitamin D to milk to prevent rickets, knowing that vitamin D enhances the absorption of calcium from the gut. Back then, oxalate research had not yet found a protective role for most of the calcium to remain in the gut to protect us from oxalate. Physicians had advised kidney stone patients to avoid calcium, but later determined that calcium in the diet was protecting patients from absorbing oxalate.
    Later studies showed that oxalate that remains in the intestines as a free anion (unbound to calcium) can and will be absorbed into the body once it reaches the colon. When this unbound oxalate is taken into the blood, there it was found to be able now to tie up free calcium that was needed to protect our bones and work in our metabolism.
    Free oxalate could a lso be taken into cells via oxalate transporters where it could disrupt calcium signaling inside cells and wreak havoc in the mitochondria and endoplasmic reticulum. Free oxalate can disrupt activity also in the nucleus where nature has supplied a specific oxalate binding protein. Is this protein sometimes overwhelmed when oxalate gets too high?
    Before I attended this celiac symposium, I had not heard that some of the autoimmune and cancer risks associated with celiac disease may still be there even with a gluten-free diet. Who was asking what else besides gluten could be contributing to these risks and were they being studied? Was oxalate one of those risks? People on our listserves that help people reduce dietary oxalate were telling us they experienced improvements in autoimmune conditions on a low oxalate diet. No one has had time to examine these reported changes formally yet, but could oxalate have a potential connection to the risks of autoimmunity or even transformed cells in celiac disease patients?
    I learned to ask these types of questions in graduate school and in the years that followed as I continued to find science that had been learned "out of order", and rejected as an important piece of the science because at the time there were missing pieces that were only discovered later. My intense study of medical literature's missing links brought to my attention so many valuable scientific discoveries that at the time they were published had been cast off as irrelevant. As I started to look intensively for more and more of these lost pieces, I made another astonishing discovery. I learned that we do not fund researchers to go digging through past scientific work to find links that may never be rediscovered after scientists with other priorities and agendas direct research efforts into other directions.
    Does science proceed linearly? Why should it? Are you personally one of the types of people that when doing a jigsaw puzzle, you first find all the outside pieces, and then start grouping colors and actually have a plan for which piece you will try to find next? My plan is to keep looking for pieces that didn't fit into models in the past to see if today's new findings will finally reveal how they now fit in well with today's insights.
    I don't think laboratory scientists or clinicians are the best equipped to do this sort of work, but organizations funding science expect that to be where this sort of integrative work will originate. I have found instead that most investigators who are up to their ears in current scientific projects or who are developing protocols for others to follow will not take very much time to dig deeply for lost pieces. There are rare exceptions to this observation. I have actually met a lot of this special breed of scientist, who loves to think outside the box and has respect for what might have been lost and loves to dig through old findings. Nevertheless, sociologists who study such things tell us that most scientific studies are never read outside of a small group of narrow interest and will only have influence for a few years. With this being the general expectations, who is left to do the work of recovering lost work from the past? Who also brings in work from other disciplines previously thought unrelated to a condition?
    In the oxalate field, molecular biologists have now discovered that oxalate shares transport with sulfate and bicarbonate, which means oxalate also gets into the regulation of pH. While these transporters regulate these ions, they also move a lot of water across cell membranes. In some places, oxalate shares transport with iodine, and of course, that makes us think of things related to the thyroid and all the histories of later onset thyroid disorders and autoimmune conditions. Pathologists found that the older you are, the more your thyroid gland will fill with oxalate, and this can be associated with a loss of thyroid activity. That makes sense now that we understand that these substrates are linked in the way the body handles them.
    But what about anemia that can develop in celiac disease? Scientists found that transferrin's carbonate ion can be replaced by oxalate if oxalate can gain access to this site at sufficient concentrations. When that happens, unlike the carbonate ion, the oxalate anion won't let go of the iron, so it sequesters iron irreversibly. This mechanism has never been thought to be related to the anemia in celiac disease.
    What about the tendency towards osteoporosis or osteopenia in celiac disease? Some remarkable studies conducted in the late 1930's (actually after Popeye made his appearance) fed groups of rats a basal diet deficient in a good calcium source, but they made up the rat "RDA" for calcium by using either turnip greens or spinach. Turnip greens are high medium in oxalate content, but spinach is extremely high. The rats fed the spinach, during their lifetime (and many died prematurely), had impaired growth (also seen with celiac disease). They had bones and teeth that wouldn't mineralize. The rats on spinach were unable to reproduce except for one litter of two pups that were quickly devoured by their mother at birth. In contrast, the rats fed turnip greens, which are roughly otherwise equivalently nutritious, completed the study in great health with shiny coats and all the perks of being a healthy rat. Did Popeye deceive us about the benefits of what has become a much more popular food, often called "the healthiest food there is?" By the way, one of these studies was conducted by Campbell Soup Company!
    Our oxalate project, which makes its home at www.lowoxalate.info with its associated support groups on Yahoo and Facebook, has now served more than 17,000 families in helping them discover for themselves how oxalate has been contributing to health issues…with problems that resolved as they brought down their body burden of oxalate. We've seen this one change fundamentally alter the course of more than twenty disorders, and these disorders are not very much alike. Some are genetic and some are probably not genetic, but are you wondering why they aren't alike if they are all associated somehow with oxalate?
    With new genetic tools and new basic science to help us, it is now a lot easier to figure that out. Members of the SLC26 family of oxalate transporters that move a special set of nutrients across cell membranes are expressed at different levels and in different combinations in different organs and cell types. Scientists are just now starting to ask the questions about how they may be regulated, or "turned on" or "turned off". When is the immune system involved in this regulation? When may we find genetic differences in the use or expression of these transporters? We already know a few observations related to their expression in the lungs and in the inner ear and in the mucosa, but at this stage in the game, there is much more science about their regulation that we don't know compared to what we already have discovered.
    We do know now that it was a mistake to think oxalate was only secreted in urine. How many studies in the past based their conclusions on urine being the only place to look? Oxalate is now known to be secreted in the lungs where scientists in Russia have been making much progress in understanding its roles in asthma and COPD, but I would just about guarantee that your immunologist or your pulmonologist doesn't know about that research yet, but it has been going on for years and years.
    Oxalate is also secreted to the skin and can cause terrible rashes. Is it related to dermatitis herpetiformis? Who has measured for oxalate in those lesions associated with gluten sensitivity? In primary hyperoxaluria, secretion of oxalate to the skin has led to serious lesions that can even turn into gangrene. People on our listserves have reported the swelling of blood vessels in the skin termed livedo reticularis, and others have described and pictured all sorts of skin lesions, including an odd appearance of glitter in the skin that appears imbedded, but glistens beautifully in the sun. No, these people were not vampires!
    Our bodies not only get oxalate from dietary sources. The body is also producing oxalate internally as a by-product of certain metabolic processes that normally keep oxalate levels low. In the genetic condition, Primary Hyperoxaluria Type I, still believed to be found in only one in a million individuals, these individuals lack a B6-dependent enzyme that ordinarily converts a normal byproduct of metabolism to a very safe amino acid. When this enzyme activity is lacking from this genetic defect or from B6 problems, oxalate builds up inside the cells where it is made and where it might produce local damage. The amount of oxalate produced with the genetic defect is so high that it spills out into the body, primarily from the liver, and produces a condition called oxalosis where oxalate damages tissues all over the body, and in the bones, and the heart, and often leads to death by kidney failure.
    Through the work of Marguerite Hatch and other scientists, we have learned that signals now being studied will instruct intestinal cells to take oxalate out of blood and secrete it into the stool. Even though a vast literature has associated inflammatory bowel diseases with producing an increased absorption of dietary oxalate through a leaky gut, that is apparently not the whole story.
    The body has mechanisms to rid itself of normal levels of excess oxalate, but in primary hyperoxaluria Type I, these efforts seem never enough to protect the body. In Mayo's database it was reported that 59% of those with this genetic disease experience abdominal pain. Oxalate is a known inflammatory molecule. Does oxalate secretion to the gut produce inflammation and pain? This certainly needs to be studied by gastroenterologists but does that discipline even know about this oxalate research? Who is showing them this science? Have you ever wondered if there is anyone who ensures that discoveries from basic science are applied by the physician to patient care when the finding isn't related to drug development?
    We humans do not have genes to degrade oxalate. That is why oxalate, once absorbed into blood can collect in our tissues and cause damage. Nature has provided a way for increased oxalate in our blood to join the contents of our intestines so that it can find and bind calcium in the gut and then can leave in the feces. That is not the only reason oxalate from blood is sent there. The gut is home to microbes that are capable of degrading oxalate. This purposeful removal of a substance toxic to humans happens only if the oxalate-loving microbes are there and healthy enough to perform this service for us. This wonderful system fails, however, in conditions like cystic fibrosis, where continuous use of antibiotics may have killed the microbes that perform this service for us. Unfortunately, even in those without cystic fibrosis, many commonly used antibiotics, like the Z-Pack, can kill our oxalate degrading microbial friends.
    Another problem is that widely used antibiotics can also kill back the biotin producing microbes in the gut. Why is that relevant to oxalate? An important class of enzymes called biotin-dependent carboxylases, were found to be invaded by oxalate when higher levels of oxalate travel to where these enzymes function. Since these enzymes function in critical roles in the mitochondrion (with only one enzyme of this type serving us in the cytosol) scientists learned that oxalate may seriously impair their enzyme activity, putting our mitochondria in great distress. Scientists also found this interference is fairly easily addressed by high doses of biotin.
    Many years ago, I realized that doses of biotin being recommended by physicians and others were in all likelihood too low to provide effective restoration of the function of biotin-dependent carboxylases whenever oxalate had become elevated in mitochondria . I read about doctors treating dystonia caused by a thiamine transport defect with high dose biotin at 5-10 mgs/kg/day. Children with this thiamine transport disorder were kept on this dose of biotin for years with no problems, but when the dose was lowered, the dystonia came back. Why are some physicians worrying about giving 5 to 20 mgs a day to grown adults?
    I can only guess that they were unaware of the literature on biotin's safety and were never able to witness how their patient's lives might change on higher doses. Competition at enzyme active sites will matter much more than blood or urine levels. Unfortunately, we have no way of measuring tissue or organelle levels of oxalate in routine patient care. Clearly, more work needs to be done in this area to see where and when higher doses are needed.
    Unfortunately, many doctors are in unfamiliar territory with higher doses of biotin, and may be unaware of biotin's track record of great safety even at very high doses. We must ask, if someone is dangerously high in oxalate, which choice will cause more harm to them, taking high dose biotin, or failing to take higher doses of biotin when that could lead to a loss of function of those important enzymes? Do scientists and doctors realize that anything which damages mitochondrial function might also lead to villous atrophy? Did elevations of oxalate happen before the changes that lead to a diagnosis of celiac disease?
    There are actually many other mitochondrial enzymes known to be inhibited by oxalate. If oxalate seriously affects mitochondrial function, what might that have to do with what else we know about celiac disease? Right now, the first two articles that come up in pubmed when searching on celiac disease and oxalate are articles that should get us thinking. The first is an article entitled, "Subclinical celiac disease and crystal­ induced kidney disease following kidney transplant". Its abstract says, "Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients." This article described a patient with hyperoxaluria, but this patient was lacking overt diarrhea, fat malabsorption, or nephrocalcinosis. The article that comes up next on this search speaks of measuring children with celiac disease, and concludes, "In contrast to adults, increased urinary excretion of oxalate was not detectable in children with celiac disease." Was that happening because oxalate that was getting into the blood was being secreted at this age more appropriately to the gut, or the lungs, or the skin, instead? Or had their oxalate been collecting in tissues like the gut, where it might be starting to impair mitochondrial function, possibly leading in time to villous atrophy?
    It would be hard not to notice that currently in the US, it is becoming popular to try gluten-free eating even if someone does not have celiac disease. That situation also describes several members of my own family who do not have celiac disease, but found out about twenty years ago that being gluten-free turned around our health so significantly that we never were tempted to go back to eating gluten. I had actually gotten the idea to try life without gluten from autism research which had been looking at a different reason to be sensitive to gluten, termed "the opiate excess theory".
    When I was at the medical library doing research when I was in graduate school, I found this theory discussed in a decades old book talking about schizophrenia. Soon I was privileged to know two of the major scientists working in this area, Paul Shattock and Kalle Reichelt. They found a protein in wheat (gliadin) and in milk (casein) that as they were digested formed peptides that had opioid activity. These peptides were capable of producing signals at opiate receptors meaning they might produce reactions or side effects seen when taking opiate medications.
    Later work also discovered opioid peptides in soy. The reason that this research might be important to celiac disease is that part of the benefit seen by removing gluten may come from eliminating these opioid signals, but these signals may continue to be a problem if you are still consuming large amounts of milk or soy.
    Recently, some further implications have appeared in this research area. Another of my autism colleagues, Richard Deth, found at his laboratory that the peptides that form opiates also block the absorption of cysteine across cell membranes. This unexpected finding probably has its biggest implications in the gut (preventing sulfur absorption) and in the brain, where sulfur is regulated a little differently. I recommend his recent paper to tell you more details, but it simply means that some of the benefits people with celiac enjoyed on a gluten-free diet may have been related to this other characteristic of opioid peptides. These same individuals may find that their health will improve even more if they controlled milk and soy.
    In the second year of our project on oxalate, I spoke at a conference in Germany and was invited for lunch in the home of a family with a child with autism on a gluten-free diet, but I noticed that this child and the children with autism I met in Germany were not doing as well as I was used to seeing in the USA. As I sat at their table, I found out that most of their gluten-free bread was made with buckwheat as a major ingredient. Buckwheat is, a very high oxalate grain. Was this keeping their son from getting better?
    Because I knew so many children with autism who had done much better than before after they eliminated gluten and casein, this to me seemed a sufficient reason not to reintroduce these foods to children already off these foods as we looked into the role of oxalate in autism. That's why, as we began our research on oxalate, I purposefully set out to test the raw ingredients being used commercially and in households for individuals on gluten and dairy-free diets. Our project discovered that there was a problem with buckwheat, amaranth, quinoa, and two late arrivals, chia seeds and hemp. We already knew oxalate was high in seeds like sesame seeds and poppy seeds, and also high in nuts like almonds which were now being made into milks for those on dairy-free diets. Soy is also high in oxalate, meaning soy has two problems—its opioid peptides and its oxalate level. In grains, most of the oxalate is in the bran, so the more "whole grain" a product is, the higher it will be in oxalate. Our listserve was literally flooded with individuals who found they got "sick" soon after they adopted what they thought was a "healthy diet". Another issue was the high levels of oxalate in chocolate and carob, which are used extensively in gluten-free "comfort foods".
    Last year, I attended a gluten-free expo in my city and picked up a cookbook full of new exciting recipes that were put together for this expo, and I saw that most of the recipes contained grains, or nuts or seasonings that were extremely high in oxalate. I couldn't help but wonder: Is this going to backfire for people, and will they recognize what is happening if by using these recipes and foods that they will find their health does not improve and may even get worse?
    In helping so many thousands of people reduce oxalate, our oxalate project has learned one thing clearly, and that is that giving someone a one page list of foods to avoid rarely successfully reduces oxalate in anyone. We have been told this most often by kidney stone patients who were given these lists by their doctors. Patients have told us hundreds of times that health improvements were not realized until they made this diet more like calorie counting. This is what we do in our support groups where people also monitor the contribution to their total oxalate level that comes from medium oxalate foods.
    This is why I would ask those reading this article to please seek our help if you wish to reduce oxalate, and do not strike out into the unknown on your own or confine yourself to the use of lists you might find on the Internet or at your doctor's office. Hundreds of Listmates have told us these lists had serious inadequacies and misinformation and little overlap with what they actually had been eating.
    We have also learned something else that is critically important. People who have been on an extremely high oxalate diet and then have reduced their diet's oxalate content too quickly, have gotten themselves in trouble. Some have ended up in emergency rooms in metabolic crisis with the doctors there unable to help them, because the doctors had never had training about why someone in this situation would get so sick.
    Even before our project started, we knew from studying the literature on those with primary hyperoxaluria, that when oxalate supply is reduced quickly by removing the liver that was putting out so much oxalate into their bodies, after replacing it with a normal liver, the amount of oxalate that suddenly began to leave the tissues of their body could potentially damage the replacement organ. Doctors have reported a very high death rate with these patients, which is reported to be much higher than death rates from other reasons for liver transplants.
    But what about what happens when reducing dietary oxalate? The food industry's recommendation of multiple fruits and vegetables has happened at the same as they began promoting many foods as super-foods and nutrient rich. Unfortunately, many of these same foods are so high in oxalate that they can keep someone from being able to retain and utilize minerals that are coming from other foods in the same meal. This can promote hyperabsorption of oxalate and increase risks of mineral imbalances. Our support groups have been deluged with individuals coming to us now with diets containing thousands of milligrams of oxalate putting their urine oxalate levels in ranges formerly seen only in the genetic hyperoxalurias. A low oxalate diet tries to keep the total oxalate load to between 40-60 mgs per day in adults As we said before, people who have been eating extremely high levels of oxalate need to reduce oxalate very slowly while the body adapts to the change. We have amassed a lot of experience with helping such individuals. The need for caution and more gradual change should not surprise us, because scientists are now telling us how quickly dietary changes can alter the function and composition of our microbial community and can also quickly alter cellular regulation of whatever enters and exits cells. These are compelling reasons to change the oxalate level slowly.
    Our website is www.lowoxalate.info. Our Yahoo group and our Facebook group are both called Trying_Low_Oxalates. We are partnering with non-profits and scientists from many fields around the world to fill in the missing science for a long list of disorders. Our work has gone far beyond autism, and we have been monitoring labwork on many conditions. We want to help make this dietary alteration as easy and safe as possible. We hope some of you readers will begin to get educated in this area. If you begin to reduce your oxalate, please let us know what reducing oxalate accomplishes for you.
    Since my early years in autism research, I have been convinced of one main principle. People with a condition will know their own bodies well. They are more likely to make important observations of change compared to a professional who comes in with too many preconceived expectations and has only a limited acquaintance with their subject's previous life.
    The first step in the scientific process really happens before scientific steps are put into use. The first "pre-step" is observation of something that does not fit old models. Frankly, after twenty years in research on autism, I don't believe the first step is best done by scientists and/or physicians. Why? Often someone new seeing a problem for the first time will notice aspects of that problem that people relying on old models will think is irrelevant and leave alone. That is why, to me, careful observations of hundreds and thousands of patients interacting can become the opportunity for forming new hypotheses that a scientist can later be recruited to test. This coordination of this volume of patient input was impossible before the internet allowed patients to find each other. But now, I think this is the most fertile field there is for making new scientific discoveries.
    Please, let's not confuse those two processes. First, we need to observe changes without layering expectations on what we see that comes from experience with only one type of patient. By looking at a broader diversity of patients, and discovering the overlap of their observations, we have a much better chance at noticing unexpected patterns that are significant. When people with no expectations of what ought to be ignored end up making the same observation time and again when they don't know each other, THEN you have something to legitimately research. At that point, the scientist can get involved with the second step, which is verifying the observations and seeing how widely they apply in one disorder or even more broadly. Using both steps, and both sets of eyes, and the marvelous ability to combine observations from thousands of individuals using the internet, we are now likely to begin to understand the complex role of oxalate in celiac disease and in many other disorders.
    From the author:
    If you have ever been diagnosed with an autoimmune disease and have been trying to lower oxalate, will you participate in the development of this science by filling out a survey?
    We would also like to find out whether reducing oxalate has affected your autoimmune condition.
    The link to our survey is here: https://www.surveymonkey.com/r/CMN5KK7
    References:
    Baker PW, Bais, R, Rofe, AM Formation of the L-cysteine-glyoxylate adduct is the mechanism by which L-cysteine decreases oxalate production from glycollate in rat hepatocytes. Biochem. J. (1994) 302, 753-757 Capolongo G, Abul -Ezz S, Moe OW, Sakhaee K . Subclinical celiac disease and crystal-induced kidney disease following kidney transplant . Arn J Kidney Dis . 2012 Oct ;60(4) :662-7 . Halbrooks PJ, Mason AB , Adams TE, Briggs SK, Everse SJ . The oxalate effect on release of iron from human serum transferrin explained . J Mol Biol. 2004 May 21;339 (1):217-26. Kohman, E.F. Oxalic acid in foods and its behavior and fate in the diet. The Journal of Nutrition, 1940 18(3): 233-246. Konstantynowicz J, Porowski T, Zoch-Zwierz W, Wasilewska J, Kadziela -Olech H, Kulak W, Owens SC, Piotrowska-Jastrzebska J, Kaczmarski M. A potential pathogenic role of oxalate in autism . Eur J Paediatr Neurol . 2012 Sep;l6(5) :485-91 Monico, CG, Persson, M, Ford CG, Rumsby, G, Milliner, DS. Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II. Kidney International, 2002 Aug;62(2):392-400. PubMed PMID: 12110000 Nishijima S, Sugaya K, Hokama S, Oshiro Y, Uchida A, Morozumi M, Ogawa Y. Effect of vitamin B6 deficiency on glyoxylate metabolismin rats with and without glyoxylate overload. Biomedical Research, 2006 Jun; 27(3):P93-P98. Novartis Foundation Symposium 273, Epithelial anion transport in health and disease: The role of the SLC26 transporters family. John Wiley and Sons, Ltd. 2006. Rare Kidney Stone Consortium Mayo Clinic. http://www.rarekidneystones.org/hyperoxaluria/physicians.html  Saccomani MD , Pizzini C, Piacentini GL, Boner AL , Peroni DG . Analysis of urinary parameters as risk factors for nephrol ithiasis in children with celiacdisease . J Urol. 2012 Aug ;188(2):566-70 . Speirs, M. The utilization of the calcium in various greens, The Journal of Nutrition, 1939 17(6), 557-564. Trivedi MS , Shah JS, Al-Mughairy S, Hodgson NW , Simms B, Trooskens GA, Van Criekinge W , Deth RC . Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences . J Nutr Biochem . 2014 Oct ;25(10) :1011- 8 .

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 12/15/2015 - Newly diagnosed with celiac disease, late in 1993 or early in 1994, I was reading a paper that turned my perception of this disease upside down. I learned that it takes more than susceptible genes and eating gluten to cause celiac disease. There is some added, as yet unknown factor in the onset of celiac disease. The report I was reading suggested that a fairly common viral infection might be that missing co-factor. It went on to say that 89% of subjects with untreated celiac disease also showed blood evidence of a particular viral infection called adenovirus 12, while fewer than 12% of control subjects showed evidence of past or present infection with this virus. It is a microbe that makes its home in our small intestines. The report went on to say that this particular virus contains an amino acid sequence that is identical to a sequence that forms part of a protein in gliadin, which is found in wheat, while similar proteins with the same triggering impact on our immune systems are also found in rye and barley. I was electrified by this insight. It offered a window through which I could begin to understand this enigmatic disease that made me react to a food that almost everyone I knew seemed to tolerate without any problems.
    I looked to see who had written the article. The lead author was listed as M. F. Kagnoff, but my attention was drawn to Donald Kasarda’s name, also listed as an author, because I had seen that name before. Several years later, I attended a CSA/USA conference in Seattle. The name of one of the speakers was familiar. After a little checking, I realized that he was the lead author of the study that had touched off my imagination.
    Dr. Kagnoff’s lecture followed immediately after a presenter who had repeatedly asserted that celiac disease is a very difficult diagnosis. Almost as soon as he got up on stage, Dr. Kagnoff said something to the effect that celiac disease is only a difficult diagnosis if you aren’t looking for it. The room suddenly became very quiet.
    The presentation went well, and he outlined the criteria for diagnosing celiac disease, and stated why he felt that it was a simple diagnosis. The speaker who followed him began by stating that celiac disease is a difficult diagnosis, despite Dr. Kagnoff’s assertions to the contrary. I left that conference with a strong sense of appreciation for Kagnoff on several levels: as a gastroenterologist, as a researcher, and as an independent thinker who was quite willing to offer a dissenting opinion where he disagreed.
    Six or seven years later, a mutual friend introduced me to Marty Kagnoff at a cocktail party in New York city. It was a pleasure to finally meet him in person. I told him that I was most impressed with, and intrigued by his work with adenovirus 12. I also told him that I enjoyed hearing his assertion, at the Seattle conference, that celiac disease is a simple diagnosis. He seemed a little surprised that I was aware of his research from more than twenty years previous, and he said that his work had been eclipsed by newer work that explored other infectious agents. He was interesting and interested, and the three of us engaged in a lively discussion about some of the politics regarding celiac disease and its diagnosis. He was brilliant, creative, and independent; all the things that a researcher should be.
    His passing is a huge loss to the medical profession, the celiac and gluten sensitive community, as well as to the biological research community. His contributions and discoveries shaped much of what we now understand about celiac disease, the intestinal mucosa, and intestinal immunity.
    Source:
    Kagnoff MF, Paterson YJ, Kumar PJ, Kasarda DD, Carbone FR, Unsworth DJ, Austin RK. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease. Gut. 1987 Aug;28(8):995-1001

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 01/26/2016 - One part of our natural protection from the microbes and toxins in our environment is the innate part of our immune systems. This includes everything from our skin, to the mucous we produce in various tissues which engulfs unwanted or harmful particles, isolating them and ultimately expelling them from the body in fecal matter and mucous, such as from our sinuses. While our immune systems have other components, it is the innate system that provides most of our protection from the world outside our bodies. The intestinal mucosa is very much a part of this system. Thus, since Hollon et al found that "Increased intestinal permeability after gliadin exposure occurs in all individuals" (1), there should be little doubt that humans are not well adapted to consuming these storage proteins from wheat, or gliadin's near relatives from rye and barley. Anyone eating these grains is opening a portal into their bloodstreams so toxins, microbes, along with undigested and partly digested proteins can enter their circulation. Without gliadin's impact, these various substances would probably not have entered the bloodstream and would have been wasted with feces.
    Just as few of us would ever consider putting fecal matter on an open wound, neither would we knowingly introduce this same material into the bloodstream through the intestinal wall. Yet, that is the net effect of humans consuming gluten grains. We are giving microbes access to our circulation. These harmful substances may be destroyed by other parts of our immune systems. Or perhaps we will develop episodic or chronic inflammation, leading to vascular damage where plaques can accumulate to cause atherosclerosis. Or the inflammation may use up available serotonin and its precursor, tryptophan, leading to depression. Or this they may cause one of the many other forms of damage that can be induced by inflammation. Or perhaps these infectious agents will manifest in other ailments, the causes of which will often remain obscure, as they degrade our health. Just one example of this risk can be found in a recent report in which antibiotic resistant staph infections were detected in 13% of pasteurized milk samples, and in 75% of raw milk samples (2). The acid in our stomachs, another part of the innate immune system, may provide some protection against this hazard. 

    On the other hand, microbes that have gained entrance into the circulation have also been implicated in some cases of arthritis, where the infectious agent binds to proteins in synovial fluid. Selective antibodies then target these complexes, causing damage to both the invader and the self tissues (3, 4).
    Toxins, especially those from insecticides and other chemicals likely to be found in or on our food supply are also cause for concern. Although most cases of organophosphate insecticide poisoning were the result of suicide attempts, these substances are widely used on a variety of food crops, and can be very dangerous (5). After all, both herbicides and pesticides are designed to kill small organisms. Because of our size, we may require more of these substances to get the job done but we, too, are organisms.
    One component of such substances is inorganic arsenic, which can also be found in natural rock deposits, some wood preservatives, rice, and sea foods, any or all of which can find its way to our bloodstreams (7) especially if we consume gluten grains. Of particular concern is that rice is often a staple of the gluten-free diet and it has been shown to have a strong affinity for inorganic arsenic, which "is a chronic, non-threshold carcinogen" (7). Thus, unlike smoking tobacco, even the smallest dose can result in cancer. Further, there are many areas of the United States where the groundwater is significantly contaminated with arsenic (8). Either drinking such water or excessive dietary reliance on rice grown in such a contaminated area can result in arsenic poisoning, as reported by Signes-Pastor et al (7) in a housewife in Saudi Arabia, who had celiac disease and relied heavily on rice. These authors first suspected dietary non-compliance until urine tests revealed an arsenic concentration at 46 times the highest value of the normal range (7). Her symptoms included: "progressive fatigue, profound watery diarrhea (12 times/d), palpitation, dry mouth, poor appetite, poor taste, sleeplessness, impaired concentration, and short-term memory" (7).

    Proteins from outside our bodies are eschewed by our selective immune systems, identifying them as foreign, and mount an attack against these "aliens". So any undigested proteins from the foods we eat, if they arrive in our bloodstream, are going to result in the mobilization of antibodies aimed at the destruction of these proteins. This sounds like a process for developing an allergic response against common foods.
    However, some proteins are worse than others. Gliadin, for instance, has long been recognized as harmful to many human cells (9). Humans also lack the necessary enzymes to fully digest it (10). Thus, after gliadin has caused increased zonulin production, leading to increased intestinal permeability, it can enter the bloodstream and travel to various tissues and organs where this undigested or partly digested family of proteins will induce one or more of their range of damaging impacts on the cells each molecule contacts. Dolfini et al have also reported that gliadin "induces an imbalance in the antioxidative mechanism of cells" (11) and it wreaks havoc on human cells by changing their shape, structure, and reducing their viability, as well as inhibiting enzyme production within the cell and/or inducing cell death (11).
    Since some humans have been consuming these grains for more than 10,000 years, one might expect that we would have evolved a digestive tract that could neutralize this threat to our wellness. Unfortunately, the issue isn't that simple. Only a small segment of the human population started cultivating gluten grains so long ago. The early development of this agriculture was also very localized and episodic. It would begin in one area then, for some unknown reason, the fields would be abandoned after some period of time. Then it would (excuse the pun) crop up in another, nearby area of the Fertile Crescent (what is now parts of Iraq, Iran, Kuwait, Syria, Lebanon, Jordan, Palestine, Israel, and Egypt). The net result was that it took some time before cereal agriculture was a thriving concern. This may be explained by the illnesses that are reflected in the bones of those early farmers (11). Gluten grains appear to have taken a much greater toll on their health than it does on us now, so some adaptation has probably occurred. Nonetheless, once grain cultivation got a good start, it spread fairly quickly across Europe, arriving in England by about 5,000 years ago.
    Populations living in environments that were not conducive to grain cultivation, either due to climate or soil conditions would wait much longer to incorporate gluten grains as a staple in their diets. Modern transportation systems were required to bring this crippling food to some doorsteps in Scandanavia, parts of Scotland and Ireland, and many other such environments throughout Europe. However, even in those halcyon days when the sun never set on the British Empire, Europeans really weren't the only people on the planet. They may have behaved as if they were, but that's an issue for another discussion. In the meantime, the bulk of the world's population had not eaten gluten grains until much more recently, when Europeans "shared" these grains almost everywhere they traveled. Most of the populations these Europeans met during their travels had also missed out on the many European plagues, including bubonic plague, smallpox, and typhoid fever, as well as the filthy living conditions that were common in Europe. These conditions had selected only those with the most vigorous immune systems to carry on as Europeans. When gifts such as smallpox-infected blankets were given to natives, these naive populations succumbed, in large numbers.
    Further, only a small percentage of these naive populations who were very recently introduced to gluten were developing celiac disease. For instance, only about 5.6% of Saharawi children of Northern Africa had developed celiac disease when tested by Dr. Catassi and colleagues some 50 years or so after they had begun to eat gluten (12).
    European "explorers" probably didn't really notice such illnesses among their grain-naive hosts. Nobody had the technology or the medical understanding to identify celiac disease or the many neurological ailments that gluten causes anyway. Many of us still deal with deep wells of medical ignorance, in the context of a very modern medical system, when it comes to our disease, so how could we expect anything more from those sea-faring Europeans of four or five centuries ago?
    Perhaps those gluten derived opioids probably felt pretty good to people who tried gluten. Whatever the reason, the rest of the world seems to have adopted Europe's dietary choices, pursuing the "comfort" of gluten grains while developing myriad forms of autoimmune disease, neurological dysfunction, gastrointestinal complaint, and a variety of other ailments. And most of the people I encounter would rather deny the health risks than give up donuts, cake, pie, and toast (13).
    Note: I'm proud to announce that I've been given the privilege of reviewing a new book that will be published early next year, under the Touchstone imprint, by Simon and Schuster. I will be writing about some interesting new insights this exciting book offers into the world of gluten sensitivity in the next issue of the Journal of Gluten Sensitivity.
    Sources:
    Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non-Celiac Gluten Sensitivity. Nutrients 2015, 7, 1565-1576. Akindolire MA, Babalola OO, and Ateba CN. Detection of Antibiotic Resistant Staphylococcus aureus from Milk: A Public Health Implication. Int. J. Environ. Res. Public Health 2015, 12, 10254-10275. Li S, Yu Y, Koehn celiac disease, Zhang Z, Su K. Galectins in the Pathogenesis of Rheumatoid Arthritis. J Clin Cell Immunol. 2013 Sep 30;4(5). Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000 Mar;83(3):207-17. Coskun R, Gundogan K, Sezgin GC, Topaloglu US, Hebbar G, Guven M, Sungur M. A retrospective review of intensive care management of organophosphate insecticide poisoning: Single center experience. Niger J Clin Pract. 2015 Sep-Oct;18(5):644-50. Hasanato RM, Almomen AM. Unusual presentation of arsenic poisoning in a case of celiac disease. Ann Saudi Med. 2015 Mar-Apr;35(2):165-7. Signes-Pastor AJ, Carey M, Meharg AA. Inorganic arsenic in rice-based products for infants and young children. Food Chem. 2016 Jan 15;191:128-34. United States Geological Survey. 2005. Arsenic in ground water in the United States. http://water.usgs.gov/nawqa/trace/arsenic/ Last Modified: Thursday, 17-Nov-2011 Hudson DA, Purdham DR, Cornell HJ, Rolles CJ. Non specific cytotoxicity of wheat gliadin components towards cultured human cells. Lancet 1976; 1: 339-341. Kagnoff M. Private communication. 2005 Dolfini E, Elli L, Roncoroni L, Costa B, Colleoni MP, Lorusso V, Ramponi S,Braidotti P, Ferrero S, Falini ML, Bardella MT. Damaging effects of gliadin on three-dimensional cell culture model. World J Gastroenterol. 2005 Oct 14;11(38):5973-7. Rätsch IM, Catassi C. Coeliac disease: a potentially treatable health problem of Saharawi refugee children. Bull World Health Organ. 2001;79(6):541-5. Cordain L. Cereal grains: humanity's double-edged sword. World Rev Nutr Diet. 1999;84:19-73.

    Dr. Rodney Ford M.D.
    Celiac.com 04/20/2016 - I am likely to be accused of gluten heresy. That is because I propose that celiac disease and gluten sensitivity usually coexist. By this I mean that they are not mutually exclusive entities.
    In other words, most people who have celiac disease are also gluten-sensitive. Many people who are gluten-sensitive are likely to develop celiac disease with continued gluten exposure (depending on their genetic markers).
    My observations show that the distinction between celiac disease and gluten-sensitivity (the gluten syndrome) is blurred. The purpose of published algorithms and decision trees are designed to separate out celiac disease from other gluten-illnesses. I suggest that this thinking is flawed.
    For example, most flow charts go something like this: (See Flow Chart 1 at left).
    People are selected for celiac-blood-tests for a number of reasons. If your blood tests are positive (and usually if you carry a DQ2/8 gene), then you get an endoscopy to confirm/deny the diagnosis. This allows you to be categorized either Yes-celiac disease or Not-celiac disease. There is no overlap. This is an "us-and-them" scenario.
    However, isolating YES-celiac disease from every other gluten problem does not take into account that people who have gluten-gut-damage may well have other manifestations of gluten-related disorders.
    Such simplistic algorithms (decision trees) strike problems at every decision point. Such as: Who should be tested? Who should be re-tested? When should these tests be done? At what age? On how much gluten? What tests should be done? What are the cut-off levels? How important is carrying the DQ2/8 genes? What about sero-negative celiac disease? How accurate are endoscopic biopsies? Who interprets the Marsh scale? How long should a gluten challenge be?
    Such simplistic algorithms (decision trees) also do not give satisfactory answers to the following questions:
    Why do 10% of people with celiac disease have little or no symptoms, despite having severe small bowel damage (villous atrophy)? This group is called "asymptomatic" celiac disease. Villous atrophy alone cannot account for the majority of gluten-related symptoms. Why do half of the people with celiac disease have autonomic nervous system dysfunction? This is the disturbance of the automatic nerve activity of your internal organs. This cannot be directly attributed to villous atrophy. Why do most people with celiac disease have some brain/mental upset, including the pervasive brain-fog? Many people have neurological disease from gluten but do not have established celiac disease. How can so many "extra-intestinal manifestations" of celiac disease be attributed to intestinal gut damage alone? I am sure that you will have witnessed strong feelings from the defenders of 'celiac-disease-is-a-stand-alone illness'. For instance, read these two opposing comments from Facebook:
    A. "I find it hard to believe that gluten intolerant people (or gluten avoiders) are as strict as us who have celiac disease." B. "I am gluten intolerant (suspected Celiac but I refuse to eat gluten in order to be tested properly) … I am incredibly strict on what I eat." The world of gluten is not black and white! But there remains a tension between those who have "biopsy-proven" celiac disease, and those people who are "gluten-intolerant". However, there is a cross-over between gluten-sensitivity/intolerance and celiac disease. There is no sharp dividing line – there is lots of grey!
    I would like to see the support groups of both celiac disease and gluten sensitivity work together with a focus on their common ground. This is already happening in some countries. Both groups promote an accurate diagnosis and a strict gluten-free diet. But I call into question the accuracy of current diagnostic methodology.
    Another comment from Facebook is a good example of these blurred lines:
    "I had an endoscopy and I have some small intestine damage: increased intraepithelial lymphocytes, shortened villi and duodenitis. The gastroenterologist said I had gluten-sensitivity but because I was not celiac (wasn't Marsh stage 3a), he said that I didn't need to be quite as careful with gluten. But I know I am super sensitive - even a small piece of chocolate with gluten in it makes me sick for a few weeks. I suspect that I either didn't have enough gluten before the endoscopy, or I am in the early stages of developing it."
    This is what I conclude:
    Both groups (people with celiac disease, and people with gluten sensitivity/intolerance) come under the umbrella category of gluten-related disorders. The term non-celiac gluten-sensitivity (NCGS) excludes those with evidence of intestinal damage from gluten. But with time and continued gluten ingestion, some of these people will develop celiac disease. NCGS is part of the gluten-related disorders spectrum (see my book: www.glutenrelateddisorder.com). Both groups have an identical list of possible symptoms. They are both equally harmed by gluten. They are indistinguishable from each other without blood tests and/or endoscopy. For both groups, my recommendation is to be zero gluten. Avoidance of cross-contamination is crucial for everyone. Both groups can be exquisitely sensitive to gluten. Some celiacs experience no symptoms from gluten, making it more of a challenge for them to remain gluten-zero. Some gluten-sensitive people do not yet have overt symptoms but are developing an inflammatory state. Many people who are gluten-sensitive produce antibodies to gluten, AGA (anti-gliadin-antibodies). There is a large literature on this. AGA-positive people are more likely to develop gluten-illnesses. AGA tests are recommended in the Fasano paper the "spectrum of gluten related disorders", for the celiac and gluten sensitivity work-up (particularly for neurological disorders). I use them on a day-to-day basis in my Clinic, and so do many other practitioners. More wheat/gluten harmful proteins have yet to be identified. Early in the development of celiac disease, the person can have significant symptoms, and they may have elevated AGA antibodies, but they may have no evidence yet of intestinal damage. At this stage these two conditions are indistinguishable. How early can you diagnose celiac disease? Do you have to wait until there is substantial intestinal damage so that you can make the classic diagnosis with villous atrophy? Or do you keep on eating gluten until the damage has occurred? Or do you go strictly gluten zero and not know if you are gluten sensitive or have early celiac disease? The HLA gene (DQ2/DQ8) cannot be used as a casting vote. It is my recommendation to abandon gluten as early as possible and not wait until you have substantial intestinal damage, which may never heal. Not only is the gluten intolerant community (this includes celiac disease) confused about gluten-illness. Also, the medical fraternity is confused. The science and clinical issues are rapidly developing whilst most medical practitioners are still looking for the classic celiac with weight loss, malabsorption, and a bloated tummy (and are using an out-of-date simplistic algorithm). Many people request celiac tests of their GPs but are denied the test. The community is much more aware of gluten related disorder than medical practitioners. Yes, there are a lot of issues to think about. These gluten-illnesses are complicated to diagnose. My prediction is that increasing numbers of people will adopt a gluten zero diet. However, almost certainly it is much more than the substance gluten that is making us sick. It will take a long time to unravel all of these strings. Most people are after an easy answer, or a drug, or a vaccine. But I'm sure that it is going to become even more complicated as we learn more. These complexities do not show up in a simplistic algorithm.
    The way for an individual to solve this is to adopt a gluten-zero diet, lifelong.

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/19/2018 - Could baking soda help reduce the inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease? Scientists at the Medical College of Georgia at Augusta University say that a daily dose of baking soda may in fact help reduce inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease.
    Those scientists recently gathered some of the first evidence to show that cheap, over-the-counter antacids can prompt the spleen to promote an anti-inflammatory environment that could be helpful in combating inflammatory disease.
    A type of cell called mesothelial cells line our body cavities, like the digestive tract. They have little fingers, called microvilli, that sense the environment, and warn the organs they cover that there is an invader and an immune response is needed.
    The team’s data shows that when rats or healthy people drink a solution of baking soda, the stomach makes more acid, which causes mesothelial cells on the outside of the spleen to tell the spleen to go easy on the immune response.  "It's most likely a hamburger not a bacterial infection," is basically the message, says Dr. Paul O'Connor, renal physiologist in the MCG Department of Physiology at Augusta University and the study's corresponding author.
    That message, which is transmitted with help from a chemical messenger called acetylcholine, seems to encourage the gut to shift against inflammation, say the scientists.
    In patients who drank water with baking soda for two weeks, immune cells called macrophages, shifted from primarily those that promote inflammation, called M1, to those that reduce it, called M2. "The shift from inflammatory to an anti-inflammatory profile is happening everywhere," O'Connor says. "We saw it in the kidneys, we saw it in the spleen, now we see it in the peripheral blood."
    O'Connor hopes drinking baking soda can one day produce similar results for people with autoimmune disease. "You are not really turning anything off or on, you are just pushing it toward one side by giving an anti-inflammatory stimulus," he says, in this case, away from harmful inflammation. "It's potentially a really safe way to treat inflammatory disease."
    The research was funded by the National Institutes of Health.
    Read more at: Sciencedaily.com

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023