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Celiac.com 07/17/2015 - 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 Open Original Shared Link 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: Open Original Shared Link 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. Open Original Shared Link 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 .

Celiac.com 11/07/2017 - Researchers still don't have much good data on the consequences of antibiotic use in early life and how that relates to the risk of certain autoimmune diseases. A team of researchers recently set out to test the association between early-life antibiotic use and islet or celiac disease autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or celiac disease. Their study is part of a larger study called The Environmental Determinants of Diabetes in the Young, or TEDDY, for short. The reasearch team enrolled HLA-genotyped newborns from Finland, Germany, Sweden, and the United States between November 20, 2004, and July 8, 2010, and analyzed data from November 20, 2004, to August 31, 2014. They also enrolled individuals from the general population, and those having a first-degree relative with T1D, with any 1 of 9 HLA genotypes associated with a risk for T1D. The team charted parental reports of the most common antibiotics, such as cephalosporins, penicillins, and macrolides, used between age 3 months and age 4 years. Islet autoimmunity and celiac disease autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. The team used Cox proportional hazards regression models to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity, and to calculate hazard ratios and 95% CIs. The team conducted tests for islet and tissue transglutaminase autoantibodies on 8,495 children (49.0% female), and 6,558 children (48.7% female) who were enrolled in the TEDDY study, and they found that antibiotic exposure and frequency of use in early life or before seroconversion did not influence the risk of developing islet autoimmunity or celiac disease autoimmunity. Additionally, cumulative use of any antibiotic during the first 4 years of life was not tied to the appearance of any autoantibody (hazard ratio , 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02). Using any of the most common antibiotics during the first 4 years of life, in any geographic region, did not influence the later development of autoimmunity for T1D or celiac disease. Based on these results, the team concluded that doctors recommending antibiotics for young children at risk for T1D or celiac disease need not be concerned that the use will lead to islet or tissue transglutaminase autoimmunity. Source: JAMA Pediatr. Published online October 9, 2017. doi:10.1001/jamapediatrics.2017.2905 The research team included Kaisa M. Kemppainen, PhD; Kendra Vehik, PhD; Kristian F. Lynch, PhD; Helena Elding Larsson, MD, PhD; Ronald J. Canepa, BSc; Ville Simell, MSc; Sibylle Koletzko, MD, PhD; Edwin Liu, MD; Olli G. Simell, MD, PhD; Jorma Toppari, MD, PhD; Anette G. Ziegler, MD, PhD; Marian J. Rewers, MD, PhD; Åke Lernmark, PhD; William A. Hagopian, MD, PhD; Jin-Xiong She, PhD; Beena Akolkar, PhD; Desmond A. Schatz, MD; Mark A. Atkinson, PhD; Martin J. Blaser, MD; Jeffrey P. Krischer, PhD; Heikki Hyöty, MD, PhD; Daniel Agardh, MD, PhD; and Eric W. Triplett, PhD; for The Environmental Determinants of Diabetes in the Young (TEDDY) Study Group. They are variously affiliated with the Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville; the Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa; the Department of Clinical Sciences, Lund University Clinical Research Center, Skåne University Hospital, Malmö, Sweden; the MediCity Laboratory, University of Turku, Turku, Finland; the Division of Paediatric Gastroenterology and Hepatology, Dr von Hauner Children's Hospital, Ludwig Maximilian University, München, Germany; the Digestive Health Institute, Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado Denver, Aurora; the Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; the Department of Pediatrics, University of Turku, Turku University Hospital, Turku, Finland; the Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland Institute of Diabetes Research, Helmholtz Zentrum München, München, Germany; the Klinikum Rechts der Isar, Technische Universität München, München, Germany; the Forschergruppe Diabetes e.V., Neuherberg, Germany; the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora; the Pacific Northwest Diabetes Research Institute, Seattle, Washington; the Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; the Department of Pediatrics, College of Medicine, University of Florida, Gainesville; the Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville; the Department of Medicine and Microbiology, New York School of Medicine, New York; the Department of Virology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; and with Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.

Celiac.com 04/06/2017 - A new study showing connections between anorexia nervosa and celiac disease, both before and after celiac diagnosis, is raising eyebrows and inviting questions. Results of the study appear in the April 3 issue of Pediatrics. Because the two conditions share a number of symptoms, including abdominal pain, bloating, diarrhea, and underweight, doctors can have some difficulty telling them apart. Until now, previous data linking anorexia with celiac disease came mostly from individual case reports. To get a better picture, Karl Mårild, MD, PhD, from the Barbara Davis Center, University of Colorado, Aurora, and colleagues conducted a cohort and case-control investigation examining the connection between celiac disease and timing of diagnosis for anorexia nervosa. To do this, the research team reviewed records from Sweden's 28 pathology departments. They looked at 17,959 cases of small intestinal biopsy-verified celiac disease in women from 1969 through 2008, and compared them with 89,379 sex- and age-matched population-based controls. The team confirmed cases of anorexia nervosa through inpatient and hospital-based outpatient records. They also looked at individuals undergoing biopsy who showed small intestinal inflammation or normal mucosa, but tested positive for celiac-related autoantibodies. They recorded educational level, socioeconomic status, and type 1 diabetes status. Their results showed that the hazard ratio for developing anorexia nervosa after a celiac diagnosis was 1.46, which fell to 1.31 beyond the first year after celiac diagnosis (with a 95% confidence interval for both). The odds ratio for association of previous anorexia nervosa diagnosis among people with a diagnosis of celiac disease was 2.18, with a 95% CI. The findings remain the same, even after the team adjusted for type 1 diabetes status and socioeconomic levels. Women who had positive celiac serology, but with no signs of villous atrophy, were also more likely to be diagnosed with anorexia nervosa, both before and after celiac diagnosis. The researchers propose three explanations for these findings: First, celiac disease may have been misdiagnosed earlier as anorexia nervosa, or vice versa. Second, it's possible that closer scrutiny of patients diagnosed with one condition may have prompted a bias in detecting the second condition. Third, it's possible that people with a shared genetic susceptibility may face a higher risk of developing both conditions. Whatever the reason behind the association, the study indicates that the connections between the two conditions are likely complex, and definitely invites further study. In the meantime, the researchers write that the "bidirectional association between diagnosis of anorexia nervosa and celiac disease warrants attention in both the initial assessment, and in the follow-up of women with these illnesses." As a result of this study, the team encourages "physicians to closely monitor these patients and calls for heightened understanding of factors that contribute to their co-occurrence." Source: Pediatrics. Published online April 3, 2017

Celiac.com 10/31/2016 - Responding to observations and reports that many patients with postural tachycardia syndrome (PoTS) adopt a gluten-free diet without medical consultation, a team of researchers recently set out to evaluate the prevalence of celiac disease and self-reported gluten sensitivity in patients with PoTS, and to compare the results against data from the local population. The research team included HA Penny, I Aziz, M Ferrar, J Atkinson, N Hoggard, M Hadjivassiliou, JN West, and DS Sanders. They are variously affiliated with the Academic Department of Gastroenterology Departments of Cardiology, Radiology, and Neurology at Royal Hallamshire Hospital, and Upperthorpe Medical Centre in Sheffield, UK. For their study, the team recruited 100 patients with PoTS to complete a questionnaire that screened for gluten sensitivity, related symptoms and dietary habits. They also screened patients for celiac disease. For comparison, they calculated local celiac prevalence from a total of 1,200 control subjects (group 1) and another 400 control subjects (group 2), frequency matched for age and sex, who completed the same questionnaire. Overall, 4/100 (4%) patients with PoTS had serology and biopsy-proven coeliac disease. This was significantly higher than the local population prevalence of celiac disease (12/1200, 1%; odds ratio: 4.1, 95% confidence interval: 1.3-13.0; P=0.03). PoTS patients also had a higher prevalence of self-reported gluten sensitivity (42 vs. 19%, respectively; odds ratio: 3.1, 95% confidence interval: 2.0-5.0; P<0.0001). This is the first study to show a possible connection between gluten-related disorders and PoTS. They note that a prospective study which examines this relationship further might promote better understanding and treatment of these conditions. Source: Eur J Gastroenterol Hepatol. 2016 Sep 7.

Celiac.com 05/08/2015 - While it's true that all people with celiac disease are intolerant to gluten, not all people who are intolerant to gluten have celiac disease. Several studies have confirmed the existence of non-celiac gluten sensitivity (NCGS), a hypersensitivity or form of gluten intolerance that causes numerous symptoms similar to those of celiac disease. There are several key differences between celiac disease and NCGS. NCGS is distinguished from celiac disease by the following factors: No Hereditary Link Unlike celiac disease, NCGS is not hereditary, and shows no genetic component. No Connection with Celiac-related Disorders Unlike celiac disease, NCGS is so far not associated with malabsorption, nutritional deficiencies, or a higher risk of autoimmune disorders or intestinal malignancies. No Immumological or Serological Markers Researchers have, as yet, identified no immunologic mechanisms or serologic markers for NCGS. That means that, unlike with celiac disease, there are no telltale screening tests that can point to NCGS. Absence of Celiac Disease or Wheat Allergy Doctors diagnose NCGS only by excluding both celiac disease, and an IgE-mediated allergy to wheat, and by the continued presence of adverse symptoms associated with gluten consumption. Diagnosing celiac disease can be challenging. Misdiagnosis is common, and final and accurate diagnosis can take years and visits to numerous doctors. Because of these key differences, non-celiac gluten sensitivity is often even more slippery and difficult to confirm than celiac disease, itself. How about you? Do you or someone you know have celiac disease or NCGS? Share your story in our comments section below. Source: US Pharmacist. 2014;39(12):44-48.

Celiac.com 04/23/2015 - It's well-known that many people with celiac disease experience neuropathy and other nerve disorders. Now, a team of Israeli researchers are cautiously proposing a link between gluten reactions and ALS. The research team, from the Tel Aviv Medical Center, believes that the gluten sensitivity seen in people with celiac disease might have a connection with ALS, or amyotrophic lateral sclerosis. Their study linking tissue transglutaminase 6 antibodies to ALS is the first study to document a connection between ALS and antibodies to a particular enzyme. Also known as Lou Gehrig's disease, ALS is a progressive disease that attacks nerve cells and pathways in the brain and spinal cord, eventually causing paralysis. In the study, researcher Vivian Drory and her team found antibodies to an enzyme produced in the brain, called tissue transglutaminase 6 (TG6), in 23 out of 150 patients with ALS, but in only five of 115 healthy volunteer subjects. Furthermore, ALS patients showed higher concentrations of those antibodies. It's well documented that people with celiac disease produce antibodies to another transglutaminase, TG2, when they eat gluten, a protein in wheat, barley and rye. Interestingly, nearly half (45%) of patients with celiac disease also produce antibodies to TG6, even when they have no neurological symptoms. Droury's team set out to evaluate the prevalence of celiac disease-related antibodies and HLA antigen alleles, as well as TG6 antibodies, in patients with ALS and healthy individuals serving as controls to determine whether a neurologic presentation of a gluten-related disorder mimicking ALS might occur in some patients. They conducted a case-control study in an ALS tertiary center, where they measured serum levels of total IgA antibodies, IgA antibodies to transglutaminase 2 (TG2) and endomysium, along with IgA and IgG antibodies to deamidated gliadine peptide and TG6 and performed HLA antigen genotyping in 150 consecutive patients with ALS and 115 healthy volunteers of similar age and sex. Study subjects did not have any known autoimmune or gastroenterologic disorder, and none was receiving any immunomodulatory medications. The team found that ALS patients with antibodies to TG6 showed the classic picture of ALS and the typical rate of disease progression. The volunteers with antibodies to TG6 showed no signs of any disease. All patients and control group participants were seronegative to IgA antibodies to TG2, endomysium, and deamidated gliadine peptide. Twenty-three patients (15.3%) were seropositive to TG6 IgA antibodies as opposed to only 5 controls (4.3%) (P = .004). The patients seropositive for TG6 showed a classic picture of ALS, similar to that of seronegative patients. The team tested fifty patients and 20 controls for celiac disease-specific HLA antigen alleles; 13 of 22 TG6 IgA seropositive individuals (59.1%) tested seropositive for celiac disease-related alleles compared with 8 (28.6%) of the 28 seronegative individuals (P = .04). Average levels of IgA antibodies to TG6 were 29.3 (30.1) in patients and 21.0 (27.4) in controls (P = .02; normal, <26). Average levels of IgA antibodies to TG2 were 1.78 (0.73) in patients and 1.58 (0.68) in controls (normal, <10). In a subset of study participants, mean levels of deamidated gliadin peptide autoantibodies were 7.46 (6.92) in patients and 6.08 (3.90) in controls (normal, <16). None of the ALS patients or volunteers had the antibodies to TG2 that are commonly associated with celiac disease, but the ALS patients were more likely to show the genetic mutations that put them at risk for celiac disease. Drory said her team has begun to study TG6 antibody levels in patients newly diagnosed with ALS, and they will be testing the effects of a gluten-free diet in some of those that test positive. However, theirs is just one report, and Drory expects it will be at least a couple of years before the team has any solid results. Her team is also inviting further input from other centers, and study of their data. In the meantime, she warns ALS patients against adopting a gluten-free diet without "clear evidence of antibodies," because any imbalance of diet might prove harmful. It's also worth remembering that an association is not the same as a cause. At least one earlier study concluded that there was no association between TG6 antibodies and either neurological disease or gluten itself. The possibility of a link between celiac disease and a degenerative nerve disease like ALS is interesting, to say the least. The findings of this team will likely invite more examination of any connection between gluten reactions and nerve disorders, so stay tuned for any follow-up news. Source: JAMA Neurol. 2015 Apr 13. doi: 10.1001/jamaneurol.2015.48.

Celiac.com 11/04/2015 - A research team that conducted an analysis of the relationship between seronegative celiac disease and immunoglobulin deficiencies also conducted a literature search on the main medical databases, which revealed that seronegative celiac disease poses a diagnostic dilemma. The research team included F. Giorgio, M. Principi, G. Losurdo, D. Piscitelli, A. Iannone, M. Barone, A. Amoruso, E. Ierardi, and A. Di Leo. They are variously affiliated with the Section of Gastroenterology at University Hospital Policlinico, Department of Emergency and Organ Transplantation at University of Bari in Bari, Italy. They note that villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers in addressing seronegative celiac disease. They also note that immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of seronegative celiac disease patients may be useful. In the team's view, tTG-mRNA was similarly increased in seropositive celiac disease and suspected seronegative celiac disease, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders. An immune deregulation, severely lacking B-cell differentiatio, underlies the association of seronegative celiac disease with immunoglobulin deficiencies. Therefore, celiac disease may be linked to autoimmune disorders and immune deficits, known as common variable immunodeficiency (CVID)/IgA selective deficiency. CVID is a heterogeneous group of antibody dysfunction, whose association with celiac disease revealed only by a positive response to a gluten-free diet. The research team suggests a possible familial inheritance between celiac disease and CVID. Selective IgA deficiency, commonly associated with celiac disease, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare, with less than 300 documented cases, and is connected to celiac disease in 5% of cases. The team diagnosed seronegative celiac disease in a patient affected by sIgMD using the tTG-mRNA assay. One-year on a gluten-free diet restored IgM levels. This study data support a link between seronegative celiac disease and immunoglobulin deficiencies, and invites researchers to take a closer look at this connection. Source: Nutrients. 2015 Sep 8;7(9):7486-504. doi: 10.3390/nu7095350

Celiac.com 09/11/2014 - What’s the relationship, if any, between eosinophilic esophagitis (EoE) and celiac disease? Research studies have produced variable results. Researchers A. J. Lucendo, Á. Arias, and J. M. Teniaso recently set out to conduct a systematic review of medical literature to determine if there’s any evidence of a connection between both diseases. They used the MEDLINE, EMBASE and SCOPUS databases to conduct electronic searches with keywords relating to EoE and celiac disease. Depending on study heterogeneity, they used random-effects models as needed (I2). To assess publication bias, they used funnel plot analysis, along with the Begg–Mazumdar, Harbord and Egger tests. Their keyword search produced 197 significant study references; 30 were included in the quantitative summary, with most showing serious methodological inconsistencies. The team found significant publication bias in favor of short studies reporting positive connections between the two diseases. The prevalence of EoE in celiac patients ranged from 0% to 10.7% (I2 = 78.9%). Rates of celiac disease in EoE varied wildly, between 0.16% and 57.1% (I2 = 89%). One high-quality, prospective, randomly selected, population-based study showed a celiac disease rate of 1.1%, with no cases of EoE. Numerous quantitative summaries of celiac prevalence suffer from clinical and methodological differences. That is, they are are not similar enough to draw good conclusions. A gluten-free diet produced histological remission of EoE in 32.1% of celiac patients (95% confidence interval, 14.9–52.2%; I2 = 52.2%), which was similar to that expected for wheat elimination in EoE patients. There are not really enough valid studies to completely rule in or out a true association between EoE and celiac disease, currently available evidence does not support any such connection. In fact, the only epidemiologically valid study indicates that these diseases are not connected. Source: Alimentary Pharmacology & Therapeutics Alimentary Pharmacology & Therapeutics Volume 40, Issue 5, pages 422–434, September 2014. DOI: 10.1111/apt.12859

Celiac.com 10/29/2012 - Celiac disease with epilepsy and cerebral calcifications, also known as CEC, is a rare form of celiac disease that is accompanied by occipital epilepsy. Past studies have suggested that the neurological symptoms could be the result of a folate deficiency, as folate levels are typically low in patients suffering from CEC. However, a recent case report indicates that as with other neurological gluten-related diseases (such as gluten ataxia), there may be some correlation between CEC and TG6 autoantibodies, indicating that the disease is autoimmune in nature. The case study focuses on a four year old boy who suffered from 30+ minute long complex partial seizures every two to three days. He was given antiepileptic drugs (carbamazepine, sodium valproate, levetiracetam), but these only slightly helped reduce seizure frequency. After one year, MRI and CT scans revealed bilateral occipital calcifications over parieto-occipital regions of the brain. The patient also suffered from chronic diarrhea: endoscopy and biopsy confirmed villous atrophy and patient tested positive for antibodies associated with celiac disease. His folate levels were also markedly low. After being placed on a gluten-free diet, the patient's symptoms, including seizures, cleared within two weeks. After the seizures had ceased, the patient was given folate supplements, and taken off antiepileptic drugs. Gluten challenge caused a relapse of all symptoms. At the time of the report, the patient had been gluten-free and seizure-free for 18 months, and showed improved behavior and reading and writing abilities. Because the patient responded so well to gluten-free diet treatment before being given folate supplements and all symptoms resumed during gluten challenge, it would seem that the neurological symptoms of CEC are the result of immune mechanisms rather than vitamin deficiencies or malabsorption. Most CEC patients have low folate levels; folate deficiency was previously thought to play a causative role in the disease, but this case study brings that conclusion into question. Furthermore, the patient tested positive for TG6 autoantibodies, which are associated with gluten ataxia (another gluten-related disease with neurological symptoms, which are an autoimmune response). More studies are required, but this case study suggests that gluten ataxia is not the only gluten-related disease with autoimmune neurological manifestations. Source: http://www.ncbi.nlm.nih.gov/pubmed/22845673

Celiac.com 07/11/2011 - Is celiac disease associated with infertility? Although some reports suggest that as much of 8% of women with unexplained infertility have celiac disease, others found no correlation between the two conditions. And there is little hard evidence that celiac disease is an actual cause of infertility. To begin to bring some clarity to this issue, Khoshbaten et al. tried to determine the prevalence of celiac disease among couples with unexplained infertility in Iran. Their results are reported in the Journal of Obstetrics and Gynaecology Research. Infertile couples were recruited in Tabriz, Iran, between October 2006 and September 2007. After a complete evaluation of their endocrine status, one hundred couples with unexplained infertility were chosen for this study. Two hundred couples with at least one child and no reproductive problems served as controls. Thirteen infertile subjects - 5 men and 8 women - had elevated levels of tissue transglutaminase antibodies, compared to eleven controls - 4 men and 7 women. Fourteen infertile subjects and eleven controls were found to be IgA deficient; of these, three of each had elevated tissue transglutaminase IgG. Based on this serology, the researchers note that the likelihood of celiac disease in infertile patients is 2.39 times higher than in controls; the frequency of celiac disease is 8% in infertile patients, compared to 3.5% in controls. Only five infertile subjects and four controls with elevated tissue transglutaminase antibodies agreed to have duodenal mucosal biopsies; the remainder had no gastrointestinal complaints or other symptoms, so they opted out of the endoscopy. According to the biopsy, celiac disease was indicated in three cases of unexplained infertility compared to one case in the control group. Previous studies have demonstrated that men with celiac disease have an increased incidence of hypogonadism, sexual dysfunction, and poor semen quality. Women with celiac disease can have major menstrual problems. Systemic diseases like celiac can exert subtle effects on the reproductive system in both genders. A gluten free diet can alleviate infertility if it is caused by nutritional imbalances due to celiac disease, such as malabsorption of zinc, selenium, iron, and folate. This Iranian study, like previous studies in Finland, Italy, Israel, and the US, thus seems to come down on the side of celiac disease, as measured by serological markers, being more significantly frequent among couples with unexplained infertility than in controls. Source: Khoshbaten M, Nejad MR, Farzady L, Sharifi N, Hashemi SH, and Rostami K. Fertility disorder associated with celiac disease in males and females: fact or fiction? J. Obstet. Gynaecol. Res. 2011.

Celiac.com 04/25/2011 - Research shows that celiac disease is associated with numerous gastric abnormalities. An international research team recently set out to examine the association between rates of celiac disease and Helicobacter pylori infection in an Iranian population of 250 patients. The research team included Mohammad Rostami Nejad BS1, Kamran Rostami MD PhD, Yoshio Yamaoka MD PhD, Reza Mashayekhi MD1, Mahsa Molaei MD, Hossein Dabiri PhD, David Al Dulaimi MD, Dariush Mirsattari MD, Homayoun Zojaji MD, Mohsen Norouzinia MD, and Mohammad Reza Zali MD FACG AGAF. The team members are variously affiliated with the Research Institute of Gastroenterology and Liver Disease, Shahid Beheshti University, M.C., in Tehran, Iran, the School of Medicine, University of Birmingham in the UK, the Department of Medicine-Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, Texas, and the Department of Gastroenterology, Alexandra Hospital, Redditch, UK. For the study, the team took topsides from the gastric antrum and duodenum. They assessed morphology and histology using the updated Sydney system and modified Marsh criteria, respectively. In order to simplify the assessment of gastric lesions, the team classified gastritis in both macroscopic and microscopic stages. They screened for anti-tissue transglutaminase antibody to determine the presence of celiac disease. Of the 250 patients, 232 (93%) showed histological evidence of Helicobacter pylori infection, while 24 patients (10%) showed histological abnormalities (Marsh I to IIIc). Of the 24 patients with histological abnormalities 20 (83%) showed Helicobacter pylori infection. Of the total 250 patients, 25 patients (10%) showed positive anti-tissue transglutaminase antibody screens, nine (3.6%) of whom showed microscopic and macroscopic enteritis (Marsh I to IIIc). Clinically, there was no way to distinguish the presentation of celiac disease from those cases infected with Helicobacter pylori. Histology, even in patients with positive antibody screens, was non-specific and not useful. The results also showed a high prevalence of Helicobacter pylori infection and chronic gastritis in the study group. However, neither was associated with celiac disease, but rather, matched average rates in Western population studies. Source: Archives of Iranian Medicine, March 2011

Celiac.com 12/15/2010 - A small study in Swedish children has found no association between early childhood psychological stress and later development of celiac disease. Previous studies have shown links between psychological stress and a number immunological diseases, such as inflammatory bowel disease. A team of researchers sought to look more closely at the connection between psychological stress in families and biopsy-proven celiac disease in children. The team included Karl Mårild, Anneli Sepa Frostell, and Jonas F. Ludvigsson. Their measure of psychological stress included factors such as serious life events, parenting stress, and parental worries. Using a questionnaire data from the ABIS study (All Babies In southeast Sweden), the team collected data on 11,000 children at one-year, and on 8,800 at two-years old. They confirmed celiac disease though observing of villous atrophy in small intestinal biopsy, and confirmed the diagnosis through patient chart data. Their data showed that no association between future celiac disease and a serious life event in the family in the child's first 1 or 2.5 years after childbirth (Odds Ratio (OR) = 0.45; 95% Confidence Interval (CI) = 0.01–2.65; P = 0.72; and OR = 1.21; 95% CI = 0.43–3.05; P = 0.64, respectively). They also found no association between celiac disease and parenting stress at age 1 year and at 2.5 years (OR = 0.40; 95% CI = 0.01–2.38; P = 0.73 and OR = 0.74; 95% CI = 0.01–4.56; P = 1.00, respectively). No children exposed to parental worries at 2.5 years were diagnosed with celiac disease before end of follow-up, compared to 25 diagnosed out of 8082 children not exposed to parental worry (OR = 0.00; 95% CI = 0.00–2.34; P = 0.64). Nor was there any associations between the combined measures of stress and celiac disease. This particular study found no association between celiac disease in Swedish children and psychological stress early in life. However, a wider and more statistically robust study is needed to entirely rule out any possible associations between early psychological stresses in children and later development of celiac disease. Source: BMC Gastroenterology. 2010;10(106)