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    Gluten-related Disorders: Not Black and White


    Dr. Rodney Ford M.D.


    • Journal of Gluten Sensitivity Spring 2016 Issue - Originally published April 14, 2016


    Image Caption: Photo: CC--hardtopeel

    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.


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    Image: Dr. Rodney FordIn 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:

    1. 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.
    2. 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.
    3. 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.
    4. 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:

    • Photo: CC--hardtopeelA. "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:

    1. 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).
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.

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    This article is great at explaining all aspects of the connection between celiac disease and gluten sensitivity.

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    The fact that so many celiacs improve in only some areas of symptoms on a strict gluten free diet also says gluten is probably not the only thing making us sick. I am tired of doctors thinking that all celiacs feel 100% normal if they are gluten free. I still have a myriad of symptoms, some debilitating, and am extremely gluten free. After 15 years on the diet, my antigliadin antibodies, once off the charts, are at normal levels, anti endomysial the same, yet Ttg remains elevated. Something is still amiss.

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    Guest Gillian

    Posted

    Forgot to say that I also suffer with Hashimotos Thyroiditis an auto-immune condition that is also helped by a gluten-free diet.

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    I have celiac disease which is definitely an auto immune disease, and because i live in America eating wheat is usually out of the question. However, there is a restaurant near me that uses wheat farmed and processed in Europe that i eat at about once a month with no issues. My girlfriend can attest to this as well, because she has the same exact problems i do. For years i had wondered if gluten (from wheat) was the problem at all, but suspected that RoundUp or a similar toxin was the culprit. Finding out that i was in fact eating European wheat every month and not getting sick proved it to me. While i will concede that there is an extremely slight chance that some people actually have a wheat gluten allergy i would venture to say that most, if not all, people are simply sensitive to toxins in wheat from the farming and processing of it.

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    Guest Claire

    Posted

    From your mouth to primary care providers' ears. My son all but stopped growing between ages 12 and 13. He had reflux but no other GI symptoms. His antibodies weren't high enough, though, so we were told he didn't have celiac disease. Six years later, his antibodies were off the charts. Diagnosis was confirmed by endoscopic biopsy. Genetic test revealed DQ2.5 genes. What happened to clinical medicine? Please, "experts", stop giving primary care providers simplistic disease presentations and testing protocols. Yes, most celiac disease patients present with classic symptoms, but many do not. If a child stops growing well, suspect celiac disease...even if he doesn't fit the typical presentation. Please.

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    Guest Linda

    Posted

    I completely agree that many people who claim to just have sensitivity (or even other illnesses, like irritable bowel syndrome) are celiac and just need to save themselves a lot misery and money and strictly avoid gluten. Most of my family are celiac, if they admit it or not. My daughter and I have stay strictly gluten free for 25yrs and my grandchildren are gluten free. We are the only healthy people in our family, literally. My sister spends huge sums of money on her family's health, when all they need to do is avoid gluten. My Mother is slowly dying because she and her doctor won't completely keep her off gluten. She has so much diarrhea that she can not maintain nutritional levels sufficient to support her life. Yet she keeps eating gluten and saying it is ok for her to just eat "less" gluten, a little bit, she says is ok...and her doctors, even the nursing home she was in, don't even seem to have enough understanding of cooking without gluten to provide her with food. At the nursing home they just slid off her plate anything they "guessed" might have gluten in it...which translated to her having only reconstituted scrambled eggs for one breakfast I knew about, and traces of other things that had been on her plat still lingered...I am appalled at the ignorance of people in positions like doctors, nutritionists, cooks in nursing homes and hospitals... in my Mother's small town it seems most people don't even know what gluten is or they think it's just another fad diet, or they otherwise don't have a clue to how serious a gluten free diet is.

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    Guest Cherri Nelson

    Posted

    I'm so happy to read this from a doctor who lays it out as more complicated than black and white between celiac and/or gluten sensitivity. I was once warned by a physician that the longer I stayed gluten free, the more sensitive I would become. I sometimes wonder these days if I'm still dealing with gluten sensitivity or if I've become a celiac based on my reactions to smaller and smaller amounts of gluten setting a host of symptoms off, some of which are painful. And I too am not going to eat gluten to take a test that can be unreliable anyway. My sister nearly died at 6 months until diagnosed with celiac in 1948. I had never been told this was something for me to watch also. It's changed my life since for the first time in my life I no longer suffer from clinical anxiety and panic attacks. You can only guess at what it did to my self esteem. Unfortunately I was in my 60s before the discovery. I so wish there would be more research on this whole issue.

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    Guest Leslie

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    The fact that so many celiacs improve in only some areas of symptoms on a strict gluten free diet also says gluten is probably not the only thing making us sick. I am tired of doctors thinking that all celiacs feel 100% normal if they are gluten free. I still have a myriad of symptoms, some debilitating, and am extremely gluten free. After 15 years on the diet, my antigliadin antibodies, once off the charts, are at normal levels, anti endomysial the same, yet Ttg remains elevated. Something is still amiss.

    What are your thoughts on gluten and grain free eating as well as limiting toxins as much as possible (if you don't already)? I have read that other grains can mimic gluten and then our bodies start attacking them too.

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    Guest s fricker

    Posted

    If you suspect you have celiac, avoiding gluten is better than getting diagnosed. Diagnosis with this autoimmune disease will mess with your qualification for life insurance.

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  • About Me

    Dr. Rodney Ford is a Pediatric Gastroenterologist. He was Professor of Pediatrics at the Christchurch School of Medicine. He runs the Children's Gastroenterology and Allergy Clinic in New Zealand. He has written a series of 7 books on gluten (www.DrRodneyFord.com). His main theory is that symptoms from gluten reactions arise from brain and nerve damage. His latest book is "The Gluten Syndrome" which encapsulates current ideas and concepts of gluten and the harm that it does.

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    Dr. Rodney Ford M.D.
    Celiac.com 07/15/2016 - This week I have noticed many blogs/articles claiming that the only illness that can be caused by gluten is celiac disease. Yes, they state that celiac disease alone needs a gluten-free diet. I totally disagree with this distorted out-of-date viewpoint. There are tens of millions of non-celiac people who testify that gluten causes them significant harm. It is my suspicion that the wheat lobby is cranking up these anti-gluten-free messages as a way of stopping wheat sales from slumping. Why else promote such a barrage of misinformation?
    As if to counter such negative press, I got this email last week:
    "Dear Dr Ford, since we had our appointment I have taken George off gluten and have noticed a huge difference in his behaviour. George is now a much more sociable and loveable little boy. He has manners, he shares and he will say sorry if he has done something wrong. Obviously he is still a 4 year old boy so I have to expect some behaviour issues and sibling rivalry. Thank you so much for giving me my little boy back." By way of explanation, George was aggressive and having difficulty learning, he was easily distractible and he was always fighting with his sister. His parents saw him as being a naughty boy, however he was displaying severe ADHD behaviours. They wondered if he might need some medication and were exploring psychological help for their family.
    However, as I have seen a lot of behaviour-disturbed children get completely better off gluten. So I tested him for celiac disease (this was negative), I then recommended a strict gluten-free trial for three months. As you have read, his parents say that there has been a dramatic change, and now see him as a "sociable and loveable little boy" – in just a few weeks!
    To me this is clear evidence that gluten can cause significant inflammatory damage to our nerves and brains. George was displaying ADHD behaviours, triggered by gluten. It is a pity that those who are ridiculing the gluten-free diet movement are attempting to deny children like George the knowledge of healing on a gluten free diet.
    Evidence points to the nervous system as the prime site of gluten damage. This theory is attractive because it gives a unifying answer that explains the following conundrums:
    a mechanism of the non-gut symptoms of celiac disease; the behaviour disturbances caused by gluten reactions; the psychiatric and personality disorders provoked by gluten; the multitude of neurological symptoms; the autonomic nervous system disturbances (often seen in people with celiac disease); why such small amounts of gluten can cause such major reactions by the amplification effect of the nervous system (not dependent on any gut damage); why gluten can create such a diverse range of symptoms. Because any agent that causes widespread neurological harm (think of multiple sclerosis and Syphilis) can generate almost any array of symptoms. Nerve and brain damage from gluten can also explain why celiac patients with extensive gut damage can be asymptomatic. The histological gut damage in celiac disease is not mediated through this neurologic system: it is caused by local toxicity to the bowel in susceptible people. If these people are not highly sensitized to gluten, then they may not experience any symptoms mediated through neural networks.
    I got mad and grumpy
    I would also like to tell you about Nick. When he was 8 years old he wrote his story down for me:
    "My name is Nick and I am eight and a half years old. I had a problem when I had gluten, so my mum found Doctor Ford to help me. He helped me get off gluten. When I tasted the first chocolate biscuit it tasted weird but now I'm getting used to it. I had troubles when I was on gluten. Every day I got mad with myself and sometimes with others. I didn't want to be mad. I was grumpy." I had dizzy spells
    I also had dizzy spells every day and I didn't feel well. They thought that I had a heart problem when I was 8. I went to the doctor and to the hospital lots and lots as they were trying to figure out what was wrong with me. I wasn't very well. When I was on gluten I had sore tummies at least twice a week.
    I am off gluten and I have more energy
    Now I am on a gluten-free diet. When I'm off gluten, I still sometimes have dizzy spells – but not usually. You might lose weight when you first start go gluten-free because you are getting used to it.
    At school I found I had to get off gluten, as I couldn't sit still on the mat. I now have got more energy to run. I can sprint now. I can sleep better too. I used to not have enough energy but now I have enough energy to sprint around the cross-country. I've achieved in my spelling now and I'm much better at school. My Doctor Ford is a nice man because he talks nicely. Tons of people need to go and see him.
    Gluten-free helps your attitude
    Please come to our diet because it helps you breath better, it helps your attitude change. It makes you be stronger. Me and my brother used to fight a lot when I was on gluten but we like one another now. I liked gluten foods but I can't have it as it's not good for me.
    In my family we have got a dog and four humans – Jordan, Dad, Mum and me. We are all gluten-free but my dad doesn't have to be gluten-free. It's unfair when my dad eats gluten and it makes me feel hungry.
    The food can be nice
    Our gingerbread bakery bakes us nice food. When I found out I was allowed to have a gluten-free birthday cake I was very happy. We go to Gingerbreads once a week. I buy chocolate chip biscuits they taste delicious. World come and be gluten-free as it makes me delighted! I love people that make yummy gluten-free foods.
    My brother says that being on a gluten-free diet is like being in China with no noodles. He finds it hard and says he just wants to be normal. I say he will get used to it.
    Nick
    Nick's mum adds:
    Prior to going gluten-free Nick had the following list of symptoms:
    Rashes Sore tummy and runny poos Very irritable Very tired – slept more than 12 hours Poor memory and learning hard work Behaviour problems – got very angry with others Bad hay fever and asthma Intolerant to dairy Dizzy spells for 6 months and not feeling well Very fussy eater. The good news is that of today (six months later), he is not having a lot of these symptoms and he is a much nicer person all around. He can now have dairy products again."
    Mum
    The implication of gluten causing neurologic network damage is immense. With estimates that at least one in 10 people are affected by gluten, the health impact in enormous. Understanding the components of the gluten syndrome is important for the health of the global community.
    Written in the spirit of cooperation and knowledge sharing. You can read many more patient stories in my book "Gluten-Related Disorder: Sick? Tired? Grumpy?" http://www.GlutenRelatedDisorder.com 

    Susan Costen Owens
    Celiac.com 07/29/2016 - Celiac is an autoimmune condition, and along with other autoimmune diseases, scientists are beginning to have a larger context for understanding what could be contributing to its immune dysregulation. In the last decades we've seen diseases becoming prevalent now that look very different from the diseases of our ancestors. The American Autoimmune and Related Diseases Association lists 159 autoimmune diseases on their website (1), but most of these diseases are very new.
    In recent years, scientists began to identify and explore a new complex that was identified within our cells and belongs to our immunological line of defense. This new player is part of innate immunity, which is also called cell-mediated immunity. This is our body's rapid responder, and its approach to immunity is more like hand to hand combat. Its role is surveillance, and it uses generalized markers to identify something as an enemy and something the immune system needs to defeat. It looks for evidence of infection from bacteria, fungi, viruses and parasites but it also analyzes cellular debris. It is looking for any sort of danger signal that conveys the message that life is not normal as it ought to be (2). This analysis can even include looking for changes in pH (3).
    The innate branch of the immune system is dependent on cells that are called phagocytes, and these cells like to engulf small pieces of things they encounter, in a process called phagocytosis. Often these cells will be breaking down those pieces it engulfs and then will returning the nutrition it contained back into the extracellular space. After fragments from outside are internalized, cells needed a way to decide if what was engulfed should lead to a stepped up immune response. That's why it is not surprising that scientists recently discovered a whole network of molecules internal to these cells that form a complex called an inflammasome. There are various types of inflammasome that cover different biological niches (4).
    What this means is that, in response to what is deemed an enemy, a phagocytic cell will gather together a distinctive list of parts to assemble into an inflammasome, and then that inflammasome will produce specific cytokines called IL-1 beta and IL-18. These chemical messengers can then go and recruit more help.
    In contrast, antibody mediated immunity is more like having an air defense. The antibodies made by this part of our immune system function more like missiles that are sent out to find a designated target.
    Vaccines are designed for the antibody side of the immune response. Future recognition of a previous invader involves selecting a piece of protein, called a peptide, that is large enough to recognize. This side of our immune response forms a memory of that peptide so that in the future, our cells will use that memory to recognize that we have seen that germ before. If the germ is recognized from a previous infection, then the immune system can respond very quickly and with more hands on deck. The piece of the intruder's identity that will be remembered is determined by our HLA type, and that is determined by a section of DNA on our sixth chromosome. The vulnerability to celiac disease is defined by the genes that are behind the formation of HLA-DQ2 and/or HLA-DQ8.
    Scientists have known for many years that these two branches of immunity compete with each other and need to stay in balance. The chemical immune messengers called cytokines will shift our immune response between a dominance of cell mediated or antibody-mediated immunity. Until very recently, all the attention in celiac was on the antibody mediated branch whose major decision-makers are T cells, but even T cells can form inflammasomes (5).
    Scientists are now studying the innate immune response to gluten. Our innate immunity relies on a specialized call type called a phagocyte. Cells of this type of include monocytes, macrophages, neutrophils, granuloctyes, mast cells, dendritic cells, osteoclasts and even migroglial cells in the brain. Phagocytic cells will incorporate debris that comes close to them into a vesicle, and that is a sort of bubble with liquid and other contents inside. This vesicle is taken into the cell through a process called endocytosis. After that, this type of cell will quickly process the contents of that vesicle probably much faster than other cell types. This competence is likely why this type of cell is given the job of surveillance for invaders. It is also is useful as a tool for recycling things from the outside that they take in. Scientists prefer to call this set of cells the professional phagocytic cells. Other cell types can be enlisted for the job of phagocytosis but they don't have that role as their main purpose. That is why this different set is called the non-professional phagocytic cells and they may also form inflammasomes but may need more stimulation. (6).
    Scientists in the last decade have done experiments to learn how inflammasomes work. These intracellular immune complexes are assembled often in response to exposures to a type of molecule called a lipopolysaccharide that can be detected after engulfing the cell membranes of invading organisms. There are many other triggers, all recognized by their ability to tell us when something inside us is not as it should be. ATP, our body's energy molecule, when it is identified as coming in from the outside, can be a trigger for the inflammasome. Engulfing this sort of molecule suggests to our phagocytes that cell death events may have occurred in the environment of that cell (7). Some of our cells have been found to extrude nucleotides in self-defense, because leftovers from that kind of event may tell the inflammasome machinery that the cell is encountering a dangerous situation (8).
    This system recognizes that certain pathogens create holes in cell walls, so when a phagocyte encounters evidence of damaged membranes with holes in them, that alone can trigger a cell danger response that enlists inflammasomes. That means two popularly used medicines that kill fungus by inserting holes in their cells, Nystatin and Amphotericin B, have by themselves been found to create this danger signal even when there is no infectious agent. Doctors and lay people need to know that many signs that are usually associated with an infection, including fever, can occur when there is nothing infectious involved (9). Another inflammasome trigger is excess alcohol which can be very damaging when it triggers inflammasomes in the nervous system. (10) Another concern is environmental contaminates like asbestos and silica which have been studied the most when they are inhaled. (11)
    Crystals of uric acid associated with gout or other cell debris can also trigger the inflammasome, as can crystals of oxalate, which may be important to celiac disease since scientists have found higher levels of oxalate in celiac sprue. These crystals must reach a critical concentration to generate this cell danger mechanism in phagocytic cells (12). In the past, nobody really was aware that oxalate could have a major effect on the immune system outside of what it does in the kidneys.
    Scientists for so many years thought the kidney alone contained cells that oxalate could influence. That's why other cell types were not studied. At least now, we realize this narrow focus had been based on some premature conclusions. We should have known to look more broadly because there was so much evidence from Primary Hyperoxaluria, a genetic disorder where a defective liver produces oxalate that travels to the whole body, creating a condition called oxalosis. That's how we know that oxalate goes all over the body. For the longest time, nobody was measuring oxalate outside of kidney disease, even though there were a few exceptions, like in people after bariatric surgery, and in celiac sprue and in cystic fibrosis, and eventually, in autism (13).
    Because there already was a literature about oxalate in celiac sprue, when our project began, we started informing the public about these links on our website, www.lowoxalate.info. More recently we have written a series of articles about oxalate in this journal, discussing the science, and also practical issues about how to reduce oxalate while on a gluten free diet. That was working with knowledge we had then, but now we know that this issue of inflammasomes has been a part of the story we didn't know, but it holds great promise of possibly addressing why there could be complications in celiac sprue that do not resolve by merely going gluten free.
    Another trigger for the inflammasome is homocysteine (14). The pathway to recycle homocysteine back to methionine is called remethylation, and this process requires both methylcobalamin and the folic acid cycle. Others on internet groups have brought attention to polymorphisms in one of the relevant enzymes, called MTHFR. This system is also tied to the process of making sulfate, taurine and glutathione, because homocysteine can be routed that direction when the body is trying to resolve oxidative stress. Many of these steps require B6, and heme is also needed to direct homocysteine towards transsulfuration. The issue of excess homocysteine may prove to be more important to our non-professional phagocytic cells that are found lining our blood vessels, because these same vessels can also take up oxalate, creating a condition of vascular swelling called livedo reticularis (15). Issues with both homocysteine and oxalate have been associated with atherosclerosis (16).
    Did your child's pediatrician recommend giving your child Tylenol before his immunizations to make him more comfortable about his body's reaction to his shots? Scientists have now found that Tylenol not only depletes our body's ability to deal with the oxidative stress from immunization, but it also turns on the inflammasome (17). The inflammasome will skew immune defense away from Th2 adaptive immunity, and that is unfortunate, in this case, because the process of developing a Th2 response was the whole point of giving a child a vaccine. Our vaccines are designed to contain adjuvants that skew the immune response in the Th2 direction (18) but some adjuvants may not be working as expected (19).
    Researchers sometimes look for the evidence that someone has developed antibodies before they will call an immunization a success. That test will ordinarily not be ordered by a pediatrician, but instead, a child will simply later be given, by default, a booster shot. Is there any chance the recommendation of Tylenol or other inflammasome activators could have impaired the antibody response in some children? Certainly, the new research on inflammasomes might suggest that in children who fail to make antibodies after a vaccine, a look at what is happening with innate immunity could be in order before assuming that these systems are working normally. Are doctors testing antibody titres or doing other immune testing in children with celiac sprue? This may be more important if such a child has developed another autoimmune condition.
    Has gluten had other ways of affecting the immune response? We have known that gluten and proteins from milk, soy, and even spinach will form opioid peptides as they are broken down. Like other opiates, these active peptides can be addictive and would be able to skew an immune response (20).Opioids can also paradoxically activate inflammasomes in the spinal column which then may provoke, amplify, and prolong pain. (21) Other work showed us that activation at the same opioid receptors that drugs use can limit our absorption of the amino acid cysteine. This amino acid is needed by our bodies in order to provide glutathione, the primary cellular antioxidant that protects us from oxidative stress, and this is especially important to save us from neurodgeneration (22).
    Why is that important? The formation of glutathione can calm down a mitochondrion that is upset enough for it to be generating reactive oxygen species (ROS). Unfortunately, scientists recently learned that the ROS produced by a mitochondrion under such stress will also trigger the inflammasome. Having adequate glutathione is especially important when our bodies are coping with the demands of immune activity, as during illness or after immunization. Unfortunately, oxalate at those times may compete with glutathione for entry into the mitochondrion at the mitochondrial dicarboxylate carrier (23).
    Until very recently, we did not know that partially digested pieces formed from gliadin could trigger the formation of the inflammasome. This occurred more in peripheral blood mononuclear cells (PBMCs) from people with celiac sprue compared to healthy donors (24). The people who did this research may not have known that people with celiac tend to be higher in oxalate than other people, and they also may not have known that oxalate by itself has been found to trigger the formation of the inflammasome. People with celiac may need to be careful about avoiding both triggers for inflammasome formation.
    In a different context, another group of scientists discovered that PBMC's exposed to titanium salts made from oxalate caused immunotoxicity when other salts of titanium did not produce that toxic effect. That experiment tells us that oxalate does enter the type of cell that was also found to respond in celiac disease to these digests of gliadin by formation of the inflammasome (25).
    The well-studied vulnerability of individuals with celiac to antibody mediated effects of gliadin came from the adaptive arm of our immunity. The HLA type is definitely known to be relevant there, but it would not be relevant to an issue of cell-mediated immunity. That is why it is a puzzle that the authors of this study did not control for oxalate by matching the control and celiac subjects for the oxalate content of their cells.
    The differences they saw in response to the gliadin digest may have required higher levels of oxalate in those cells. Do we know? If that could be the case, then it becomes possible that the response they recorded in celiac cells might also happen in those who are higher in oxalate for other reasons, but who lack the HLA risk genes that are definitional of celiac. We simply cannot tell if the risk of inflammasome activation in their experiment involved having the oxalate content of these cells also working in some kind of synergism with gluten. It is important to note that here we are talking about oxalate that this type of cell may have accumulated earlier in its life or during its time in the blood. Here we are not talking about oxalate that someone may have just eaten.
    It is possible that an inflammasome-mediated function could explain why there are so many people who don't have celiac disease discovering that removing gluten from the diet makes them feel better. The academic community and others are still having a hard time believing this story (26), and cannot understand the recent popularity of gluten free foods in the general population.
    A different reason for thinking about a possible synergism between a gluten free and a reduced oxalate diet came from a recent poll done by the Oxalate Project at www.lowoxalate.info. Those results revealed that the majority of those who reported positive effects in their autoimmune disease by reducing oxalate had been extremely high in oxalate before they reduced oxalate. Curiously, 58% of those responding to the poll said they were also gluten free, but only 16% had celiac sprue. Those who were both gluten free and low oxalate reported a 10% higher positive effect from reducing oxalate than those who were not also gluten free. That could be important.
    Many scientists still think a standard American diet will keep oxalate below 200 mgs a day, but 84% of the individuals answering that poll said that they started out with levels of oxalate over 300 mgs a day. Recent changes in eating habits for high oxalate foods may have been the result of powerful advertising that has been telling people that high oxalate foods are the healthiest foods available. Anonymous poll data has no way to be verified, and that fact keeps us from assuming that we can derive information from this poll about oxalate's role (if any) in contributing to their autoimmune condition. Even so, the poll told us that out of all respondents, 73% reported a positive effect in their autoimmune condition by reducing oxalate, but those with celiac sprue (some who had other autoimmune conditions) did much better. 88% of them reported a positive effect on their autoimmune condition. That was actually a higher percentage than what was recorded for any of the other autoimmune conditions. Does that mean that it might be important for autoinflammatory processes to be careful about both gluten and oxalate? (27) We may learn the answer to that question as more people with these issues try both dietary changes together.
    Some scientists now are generating data that they feel supports the idea that excessive activity of inflammasomes could be related to the etiology of autoimmune disease (28). The changes that the inflammasome makes to our bodies can be harsh, and in fact, some scientists studied sepsis in animals and found that just by blocking inflammasome activity by various inhibitors, they could save those animals from a certain death. The irony is that the animals were still infected, but survived anyway. That means that what had been killing them was their immunological response to infection instead of the infection itself. This type of research is still very new, but it may change some of our assumptions (29).
    What interventions have scientists found that will suppress inflammasome activity? The good news is that a lot of their research has involved supplements that anyone can buy in a health food store, and some people were already using them for different reasons. One of those items is resveratrol. When it was first studied, it seemed to have been made out of red wine, mostly, but our project has discovered that commercially, the usual product is made from an herb called Japanese knotwood, which is known to be high in oxalate (30). The Oxalate Project has not yet tested the oxalate content of commercially available brands of resveratrol to see how much oxalate ends up in a capsule, but that testing is on its agenda.
    The supplement quercitin is also an inflammasome inhibitor (31). CoQ10 is another supplement that has become widely available in drug stores and health food stores because it is needed to correct a mitochondrial problem created by statin drugs. Fortunately, CoQ10 also inhibits the inflammasome, mainly by keeping the mitochondrion happier and better protected from the need to generate reactive oxygen species (32). A popular source of sulfur called MSM (methylsulfonylmethane) also was found to inhibit inflammasomes (33). So has its close cousin DMSO, a solvent that was once used as a delivery system for secretin, when it was proposed as a treatment for autism (34, 35).
    Another exciting inhibitor is 3-hydroxybutyrate, which is one of the two ketones (along with acetoacetate) that our bodies make in ketosis (36). Ketosis occurs when the body is not getting enough energy from carbohydrate, and it switches into a mode of burning fat, and that produces these ketones. Some people will try to induce this switch in metabolism on purpose, like those dealing with seizures who find the seizures are controlled with a ketogenic diet. If the change that this ketogenic diet accomplished was due to down regulation of inflammasome activity, that might bring new hope or strategies to mind for individuals where this diet treatment by itself failed. Such individuals may have had a different environmental component that was still activating inflammasomes in spite of their use of the use of the ketogenic diet. This mechanism may point to yet another reason that obesity, which may have come from excess consumption of carbohydrate, has been linked with inflammasome activation (37).
    We can hope that more investigation of other activators and other inhibitors for those with seizures might yield better success. Also, the association with ketosis may explain a previously overlooked benefit experienced by people who were exercising the discipline of fasting…the age-old tradition that comes from many cultures. These traditions are more striking when realizing that obesity can activate inflammasomes and inflammasomes are thought to be behind the roots of metabolic syndrome and diabetes (38, 39).
    Pharma does have some drugs already in its cabinet which scientists have found will inhibit inflammasomes. There are probably more such drugs in the pipeline and we may soon hear advertisements for this new class of drugs. Our Oxalate project has already begun to hear of some doctors and hospitals using the over the counter inhibitors resveratrol or coQ10 to successfully protect patients who were at risk for developing sepsis.
    More research obviously needs to be done in this area and this new frontier has become very attractive to scientists. One of the first big questions they may need to ask is whether our health care protocols in Western medicine have led to over-stimulating this arm of immunity by emphasizing killing strategies with antimicrobial therapies or other drugs that may leave crystals or other debris behind. Why might that have been a problem?
    Phagocytes are upset about cellular debris and disrupted membranes. Some scientists have been finding that our bodies may stay healthier by tolerating some infections rather than experiencing the excessive immune activity that comes from activating inflammasomes. It will take a long time for some of these scientific ideas to trickle down and begin persuading doctors to make changes in their prescribing habits for antibiotics and other antimicrobials. Some doctors and other practitioners are already finding that inflammasome inhibitors could be an appropriate adjunct therapy during antibiotics. Of course, since this is such a new scientific area to study, it may take years before proper clinical studies can be done to address all these issues.
    In the meantime, it seems wise for anyone prone to autoimmune disease to avoid triggers for inflammasomes that are easy to avoid. This would include things like being overweight, eating foods that encourage uric acid formation (and the risks known for gout). It could include situations that encourage the body to make oxalate and that could include deficiencies of B6 or thiamine, or excess use of Vitamin C. It could come from excess dietary oxalate. We also need to consider the use of drugs or supplements that are known to form crystals in blood, or Tylenol, or antifungals that punch holes in cell membranes. We need to be vigilant about our status for homocysteine. We need to be careful about our level of consumption of alcoholand our exposureto other environmental contaminants. In time, we will learn of many other triggers.
    If there is a suspicion that inflammasomes are related to a disease process that we find in our bodies, then we should at least think about using one of the over the counter and safe and well-studied inflammasome suppressors. As the research continues, we can hope that scientists studying in this area will show us more ways to dial down the frequency and the unpleasant symptoms and other consequences of autoimmune disease and autoinflammation.
    References:
    1. (http://www.aarda.org/autoimmune-information/list-of-diseases/)
    2. Doria A, Zen M, Bettio S, Gatto M, Bassi N, Nalotto L, Ghirardello A, Iaccarino L, Punzi L. Autoinflammation and autoimmunity: bridging the divide. Autoimmun Rev. 2012 Nov;12(1):22-30. doi: 10.1016/j.autrev.2012.07.018. Epub 2012 Aug 2. Review. PubMed PMID: 22878274.
    3. Rajamäki K, Nordström T, Nurmi K, Åkerman KE, Kovanen PT, Öörni K, Eklund KK. Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem. 2013 May 10;288(19):13410-9. doi: 10.1074/jbc.M112.426254. Epub 2013 Mar 25. PubMed PMID: 23530046; PubMed Central PMCID: PMC3650379.
    4. Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L, Martinon F, van Bruggen R, Tschopp J. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem. 2007 May;55(5):443-52. Epub 2006 Dec 12. PubMed PMID: 17164409.
    5. Arbore G, West EE, Spolski R, Robertson AA, Klos A, Rheinheimer C, Dutow P, Woodruff TM, Yu ZX, O'Neill LA, Coll RC, Sher A, Leonard WJ, Köhl J, Monk P, Cooper MA, Arno M, Afzali B, Lachmann HJ, Cope AP, Mayer-Barber KD, Kemper C. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⺠T cells. Science. 2016 Jun 17;352(6292):aad1210. doi: 10.1126/science.aad1210. PubMed PMID: 27313051.
    6. Paoletti, R.; Notario, A.; Ricevuti, G., eds. (1997). Phagocytes: Biology, Physiology, Pathology, and Pharmacotherapeutics. New York: The New York Academy of Sciences. ISBN 1-57331-102-2.
    7. Kim JJ, Jo EK. NLRP3 inflammasome and host protection against bacterial infection. J Korean Med Sci. 2013 Oct;28(10):1415-23. doi: 10.3346/jkms.2013.28.10.1415. Epub 2013 Sep 25. Review. PubMed PMID: 24133343; PubMed Central PMCID: PMC3792593.
    8. Coutinho-Silva R, Ojcius DM. Role of extracellular nucleotides in the immune response against intracellular bacteria and protozoan parasites. Microbes Infect. 2012 Nov;14(14):1271-7. doi: 10.1016/j.micinf.2012.05.009. Epub 2012 May 23. Review. PubMed PMID: 22634346; PubMed Central PMCID: PMC4110109.
    9. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010 Oct 15;330(6002):362-6. doi: 10.1126/science.1195491. Erratum in: Science. 2011 Mar 25;331(6024):1517. PubMed PMID: 20947763.
    10. Lippai D, Bala S, Petrasek J, Csak T, Levin I, Kurt-Jones EA, Szabo G. Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation. J Leukoc Biol. 2013
    Jul;94(1):171-82. doi: 10.1189/jlb.1212659. Epub 2013 Apr 26. PubMed PMID: 23625200; PubMed Central PMCID: PMC3685015.
    11. Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.Science. 2008 May 2;320(5876):674-7. doi:
    10.1126/science.1156995. Epub 2008 Apr 10. PubMed PMID: 18403674; PubMed Central PMCID: PMC2396588.
    12. Petrasek J, Iracheta-Vellve A, Saha B, Satishchandran A, Kodys K, Fitzgerald KA, Kurt-Jones EA, Szabo G. Metabolic danger signals, uric acid and ATP, mediate inflammatory cross-talk between hepatocytes and immune cells in alcoholic liver disease. J Leukoc Biol. 2015 Aug;98(2):249-56. doi: 10.1189/jlb.3AB1214-590R. Epub 2015 May 1. PubMed PMID: 25934928; PubMed Central PMCID: PMC4501673.
    13. Owens SC. What is the Relationship Between Oxalate and Celiac Disease?. Journal of Gluten Sensitivity. Spring 2015; 14(2):1-11.
    14. Xi H, Zhang Y, Xu Y, Yang WY, Jiang X, Sha X, Cheng X, Wang J, Qin X, Yu J, Ji Y, Yang X, Wang H. Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells. Circ Res. 2016 May 13;118(10):1525-39. doi: 10.1161/CIRCRESAHA.116.308501. Epub 2016 Mar 22. PubMed PMID: 27006445; PubMed Central PMCID: PMC4867131.
    15. Shih HA, Kao DM, Elenitsas R, Leyden JJ. Livedo reticularis, ulcers, and peripheral gangrene: cutaneous manifestations of primary hyperoxaluria. Arch Dermatol. 2000 Oct;136(10):1272-4. PMID: 11030785.
    16. Faure V, Dou L, Sabatier F, Cerini C, Sampol J, Berland Y, Brunet P, Dignat-George F. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost. 2006 Mar;4(3):566-73. Epub 2005 Dec 23. PubMed PMID: 16405517.
    17. Jaeschke H, Williams celiac disease, Ramachandran A, Bajt ML. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 2012 Jan;32(1):8-20. doi: 10.1111/j.1478-3231.2011.02501.x. Epub 2011 Mar 14. Review. PubMed PMID: 21745276; PubMed Central PMCID: PMC3586825.
    18. Quandt D, Rothe K, Baerwald C, Rossol M. GPRC6A mediates Alum-induced Nlrp3 inflammasome activation but limits Th2 type antibody responses. Sci Rep. 2015 Nov 25;5:16719. doi: 10.1038/srep16719. PubMed PMID: 26602597; PubMed Central PMCID: PMC4658484.
    19. Franchi L, Núñez G. The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur J Immunol. 2008 Aug;38(8):2085-9. doi: 10.1002/eji.200838549. PubMed PMID: 18624356; PubMed Central PMCID: PMC2759997.
    20. 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. doi: 10.1016/j.jnutbio.2014.05.004. Epub 2014 Jun 6. PubMed PMID: 25018147; PubMed Central PMCID: PMC4157943.
    21. Grace PM, Strand KA, Galer EL, Urban DJ, Wang X, Baratta MV, Fabisiak TJ, Anderson ND, Cheng K, Greene LI, Berkelhammer D, Zhang Y, Ellis AL, Yin HH, Campeau S, Rice KC, Roth BL, Maier SF, Watkins LR. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3441-50. doi:
    10.1073/pnas.1602070113. Epub 2016 May 31. PubMed PMID: 27247388; PubMed Central PMCID: PMC4914184.
    22. Johnson WM, Wilson-Delfosse AL, Mieyal JJ. Nutrients. Dysregulation of glutathione homeostasis in neurodegenerative diseases.2012 Oct 9;4(10):1399-440. doi: 10.3390/nu4101399. Review.PMID:23201762
    23. Chen Z, Lash LH. Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers. J Pharmacol Exp Ther. 1998 May;285(2):608-18. PubMed PMID: 9580605.
    24. Palová-Jelínková L, Dáňová K, Drašarová H, DvoÅ™ák M, Funda DP, Fundová P, Kotrbová-Kozak A, ÄŒerná M, Kamanová J, Martin SF, Freudenberg M, TuÄková L. Pepsin digest of wheat gliadin fraction increases production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB signaling pathway and an NLRP3 inflammasome activation. PLoS One. 2013 Apr 29;8(4):e62426. doi: 10.1371/journal.pone.0062426. Print 2013. PubMed PMID: 23658628; PubMed Central PMCID: PMC3639175.
    25. Di Giampaolo L, Di Gioacchino M, Ponti J, Sabbioni E, Castellani ML, Reale M, Toto E, Verna N, Conti P, Paganelli R, Boscolo P. "In vitro" comparative immune effects of different titanium compounds. Int J Immunopathol Pharmacol. 2004 May-Aug;17(2 Suppl):115-22. PubMed PMID: 15345202.
    26. Rakhimova M, Esslinger B, Schulze-Krebs A, Hahn EG, Schuppan D, Dieterich W. In vitro differentiation of human monocytes into dendritic cells by peptic-tryptic digest of gliadin is independent of genetic predisposition and the presence of celiac disease. J Clin Immunol. 2009 Jan;29(1):29-37. doi: 10.1007/s10875-008-9228-x. Epub 2008 Aug 12. PubMed PMID: 18696220.
    27. Owens SC, de La Garza P. Autoimmunity Survey. [Other]. Palo Alto, California, USA: Survey Monkey, Inc.; 2016 March. Available from: www.surveymonkey.com.
    28. Shaw PJ, McDermott MF, Kanneganti TD. Inflammasomes and autoimmunity. Trends Mol Med. 2011 Feb;17(2):57-64. doi: 10.1016/j.molmed.2010.11.001. Epub 2010 Dec 14. Review. PubMed PMID: 21163704; PubMed Central PMCID: PMC3057120.
    29. Sui DM, Xie Q, Yi WJ, Gupta S, Yu XY, Li JB, Wang J, Wang JF, Deng XM. Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1β Axis in Microglia. Mediators Inflamm. 2016;2016:1045657. doi: 10.1155/2016/1045657. Epub 2016 Jan 26. PubMed PMID: 26924896; PubMed Central PMCID: PMC4746398.
    30. Chen H, Tuck T, Ji X, Zhou X, Kelly G, Cuerrier A, Zhang J. Quality assessment of Japanese knotweed (Fallopia japonica) grown on Prince Edward Island as a source of resveratrol. J Agric Food Chem. 2013 Jul 3;61(26):6383-92. doi: 10.1021/jf4019239. Epub 2013 Jun 19. PubMed PMID: 23742076.
    31. Hu QH, Zhang X, Pan Y, Li YC, Kong LD. Allopurinol, quercetin and rutin ameliorate renal NLRP3 inflammasome activation and lipid accumulation in fructose-fed rats. Biochem Pharmacol. 2012 Jul 1;84(1):113-25. doi: 10.1016/j.bcp.2012.03.005. Epub 2012 Mar 16. PubMed PMID: 22426011.
    32. Cordero MD, Alcocer-Gómez E, Culic O, Carrión AM, de Miguel M, Díaz-Parrado E, Pérez-Villegas EM, Bullón P, Battino M, Sánchez-Alcazar JA. NLRP3 inflammasome is activated in fibromyalgia: the effect of coenzyme Q10. Antioxid Redox Signal. 2014 Mar 10;20(8):1169-80. doi: 10.1089/ars.2013.5198. Epub 2013 Sep 19. PubMed PMID: 23886272; PubMed Central PMCID: PMC3934515.
    33. Ahn H, Kim J, Lee MJ, Kim YJ, Cho YW, Lee GS. Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Cytokine. 2015 Feb;71(2):223-31. doi: 10.1016/j.cyto.2014.11.001. Epub 2014 Nov 21. PubMed PMID: 25461402.
    34. Ahn H, Kim J, Jeung EB, Lee GS. Dimethyl sulfoxide inhibits NLRP3 inflammasome activation. Immunobiology. 2014 Apr;219(4):315-22. doi: 10.1016/j.imbio.2013.11.003. Epub 2013 Nov 22. PubMed PMID: 24380723.
    35. Lamson DW, Plaza SM. Transdermal secretin for autism - a case report. Altern Med Rev. 2001 Jun;6(3):311-3. PubMed PMID: 11410075.
    36. Netea MG, Joosten LA. Inflammasome inhibition: putting out the fire. Cell Metab. 2015 Apr 7;21(4):513-4. doi: 10.1016/j.cmet.2015.03.012. PubMed PMID: 25863243.
    37. Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015 Nov 5;6:262. doi: 10.3389/fphar.2015.00262. eCollection 2015. Review. PubMed PMID: 26594174; PubMed Central PMCID: PMC4633676.
    38. Jin C, Flavell RA. Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol. 2013 Aug;132(2):287-94. doi: 10.1016/j.jaci.2013.06.022. Review. PubMed PMID: 23905917.
    39. Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2013 Jan;62(1):194-204. doi: 10.2337/db12-0420. Epub 2012 Oct 18. PubMed PMID: 23086037; PubMed Central PMCID: PMC3526026.

    Dr. Rodney Ford M.D.
    Celiac.com 10/12/2016 - How early can you diagnose celiac disease? This is a most challenging question for everyone: children, parents, pediatricians, gastroenterologists and many other health professionals. This is because, like so many other diseases, celiac disease is a progressive condition that slowly creeps up on you. In addition, there is disagreement about what constitutes a definitive diagnosis of celiac disease. What if the small bowel biopsy result is at odds to the blood test results?
    It is my opinion that the fundamental diagnostic requirements for celiac disease remain unresolved. This makes early diagnosis problematic!
    Do you keep waiting (whilst suffering from symptoms) for classic gut damage to be visible in a bowel biopsy before adopting a gluten-free diet? Or do you recognize the early onset of celiac disease and go gluten-free prior to this gut damage occurring? Will you be accused of "masking" celiac disease if you are an early gluten-free adopter?
    Currently, most guideline protocols require a definitive diagnosis of celiac disease by demonstrating small bowel tissue damage. This is achieved by performing and upper gastrointestinal endoscopy, taking a tissue biopsy of the mucous lining of the small bowel, and then showing specific tissue damage (villus atrophy) under the microscope: this is the small bowel biopsy procedure.
    However there is significant controversy about the accuracy and necessity of a small bowel biopsy test. We will have a close look at the difficulties and shortcomings of these tests. But first, let's look at these diagnostic problems in relation to Francesca.
    Meet Francesca who is highly at risk of celiac disease
    So how early could we diagnose Francesca's celiac disease? She has just turned 3-years-old. Her mother has celiac disease, diagnosed over 10 years ago. So mum bought Francesca for my opinion because she had started to have some loose bowel motions (runny poops), although sometimes she did have hard bowel motions, which were difficult to pass. She also had a big distended tummy, was getting more cranky, and a bit more tired. Because of mother's celiac disease, Francesca was already consuming a smaller amount of gluten, although she was eating at least one slice of normal wheat gluten bread each day. Her mother's question was: "Has Francesca now developed celiac disease?" This problem confronts me most days in the Clinic.
    How should I investigate and manage her illness?
    What blood tests should I request? How do I interpret her results? Should I organize a small bowel biopsy? Do we look for early evidence of gluten problems, or do we wait for end stage celiac damage? Should she go on a gluten-free diet now? Should we be concerned about "masking" celiac disease? Francesca's blood tests show:
    She does carry the HLA gene DQ2: this makes her a likely candidate for developing celiac disease. The tissue-damage antibodies were normal: the tTG (tissue Trans-Glutaminase) levels were low normal, but the IgG-DGP (Diamidated Gliadin Peptide) levels were borderline (18 units, with a normal range 0-20). Her EMA (Endomesial Antibody) was negative: the borderline DGP is very suspicious and evidence of early celiac disease. IgG-AGA (Anti-Gliadin-Antibody) level was moderately raised: showing that she has developed an immune response to gluten. She has not had an endoscopy: with her tissue damage antibodies at low levels, the likelihood of abnormal tissue histology is very low. My opinion
    In my opinion, this child is at extreme risk of developing celiac disease. I would like to see her on a strict gluten zero. However, it is now up to her parents to decide whether they will wait until she actually develops gut damage, or do something now to prevent her getting a serious disease.
    What would you do if she were your child? Well her parents decided to place her gluten-free and they saw a big change for the better in just a few weeks. Her bowels become normal, her energy levels improved and she is now a happy girl.
    So what is her diagnosis? I call her early celiac disease. Others would say she has non-celiac gluten-sensitivity. Some would claim that I am unwarranted to suggest a gluten-free diet until she has a positive biopsy and they accuse me of "masking" celiac disease by treating her symptoms.
    Why let Francesca unnecessarily suffer whilst waiting for her to get progressively sicker until we can get a tissue diagnosis?
    Written in the spirit of cooperation and knowledge sharing. You can read many more patient stories in my book "Gluten-Related Disorder: Sick? Tired? Grumpy?" (www.GlutenRelatedDisorder.com).

  • Recent Articles

    Roxanne Bracknell
    Celiac.com 06/22/2018 - The rise of food allergies means that many people are avoiding gluten in recent times. In fact, the number of Americans who have stopped eating gluten has tripled in eight years between 2009 and 2017.
    Whatever your rationale for avoiding gluten, whether its celiac disease, a sensitivity to the protein, or any other reason, it can be really hard to find suitable places to eat out. When you’re on holiday in a new and unknown environment, this can be near impossible. As awareness of celiac disease grows around the world, however, more and more cities are opening their doors to gluten-free lifestyles, none more so than the 10 locations on the list below.
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    The full top ten gluten-free cities are shown in the graphic below:
     

    Jefferson Adams
    Celiac.com 06/21/2018 - Would you buy a house advertised as ‘gluten-free’? Yes, there really is such a house for sale. 
    It seems a Phoenix realtor Mike D’Elena is hoping that his trendy claim will catch the eye of a buyer hungry to avoid gluten, or, at least one with a sense of humor. D’Elena said he crafted the ads as a way to “be funny and to draw attention.” The idea, D’Elena said, is to “make it memorable.” 
    Though D’Elena’s marketing seeks to capitalizes on the gluten-free trend, he knows Celiac disease is a serious health issue for some people. “[W]e’re not here to offend anybody….this is just something we're just trying to do to draw attention and do what's best for our clients," he said. 
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    "Buying can sometimes be the most stressful thing you do in your entire life so why not have some fun with it," he said. 
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    Read more at Arizonafamily.com.

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    Bakery On Main started in the small bakery of a natural foods market on Main Street in Glastonbury, Connecticut. Founder Michael Smulders listened when his customers with Celiac Disease would mention the lack of good tasting, gluten-free options available to them. Upon learning this, he believed that nobody should have to suffer due to any kind of food allergy or dietary need. From then on, his mission became creating delicious and fearlessly unique gluten-free products that were clean and great tasting, while still being safe for his Celiac customers!
    Premium ingredients, bakeshop delicious recipes, and happy customers were our inspiration from the beginning— and are still the cornerstones of Bakery On Main today. We are a fiercely ethical company that believes in integrity and feels that happiness and wholesome, great tasting food should be harmonious. We strive for that in everything we bake in our dedicated gluten-free facility that is GFCO Certified and SQF Level 3 Certified. We use only natural, NON-GMO Project Verified ingredients and all of our products are certified Kosher Parve, dairy and casein free, and we have recently introduced certified Organic items as well! 
    Our passion is to bake the very best products while bringing happiness to our customers, each other, and all those we meet!
    We are available during normal business hours at: 1-888-533-8118 EST.
    To learn more about us at: visit our site.

    Jefferson Adams
    Celiac.com 06/20/2018 - Currently, the only way to manage celiac disease is to eliminate gluten from the diet. That could be set to change as clinical trials begin in Australia for a new vaccine that aims to switch off the immune response to gluten. 
    The trials are set to begin at Australia’s University of the Sunshine Coast Clinical Trials Centre. The vaccine is designed to allow people with celiac disease to consume gluten with no adverse effects. A successful vaccine could be the beginning of the end for the gluten-free diet as the only currently viable treatment for celiac disease. That could be a massive breakthrough for people with celiac disease.
    USC’s Clinical Trials Centre Director Lucas Litewka said trial participants would receive an injection of the vaccine twice a week for seven weeks. The trials will be conducted alongside gastroenterologist Dr. James Daveson, who called the vaccine “a very exciting potential new therapy that has been undergoing clinical trials for several years now.”
    Dr. Daveson said the investigational vaccine might potentially restore gluten tolerance to people with celiac disease.The trial is open to adults between the ages of 18 and 70 who have clinically diagnosed celiac disease, and have followed a strict gluten-free diet for at least 12 months. Anyone interested in participating can go to www.joinourtrials.com.
    Read more at the website for Australia’s University of the Sunshine Coast Clinical Trials Centre.

    Source:
    FoodProcessing.com.au

    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