Tuesday, April 5, 2011

What No One Is Saying About Zonulin -- Is Celiac About More Than Genes and Gluten?

by Chris Masterjohn

In my last gluten post, I discussed why the ex vivo results of Dr. Fasano's 2006 study cannot logically be construed to show that gluten causes leaky gut in people without celiac disease, and why the available evidence suggests that people considered to have non-celiac gluten sensitivity do not have leaky gut.

Nevertheless, this study is a goldmine of valuable ideas that no one is touching.

Not all of the study's results should be considered ex vivo.  They took intestinal tissue from celiacs in remission and from non-celiac controls with digestive complaints, and measured the amount of zonulin in those tissues before performing any experiments on them.

Remarkably, they found that celiacs produce 30 times as much zonulin as non-celiacs, even though the non-celiacs were not eating gluten-free diets while the celiacs had been off gluten for over two years!

Here's a graph of their data:

This is remarkable because even though the point of the study was to show that gluten increases zonulin production, the controls were eating gluten yet had infinitesimal levels of zonulin production, while the celiacs had not eaten gluten for at least two years yet still had very high levels of zonulin production.  This suggests that something besides gluten may be causing zonulin production in celiacs.

They found similar, though less dramatic, results for intestinal permeability:

Here they measured trans-epithelial electrical resistance (TEER) of intestinal tissue taken from gluten-free celiacs and gluten-eating controls.  TEER is an estimation of the leakiness of the gut, where a lower value indicates a greater level of leakiness or permeability.  They found that tissues taken from controls who had been eating gluten had three-fold less leakiness compared to celiacs who had been off gluten for over two years.  This, again, suggests that something besides gluten may be contributing to leaky gut in people with celiac.

What is causing the persistently elevated zonulin in celiacs, or the somewhat less severe persistent elevation in gut permeability?  It could just be that these subjects need to adhere to a gluten-free diet more strictly or for much longer than two years to fully resolve these issues.  Or, it may be that certain types of intestinal dysbiosis (improper balance of bacteria and yeasts in the intestines) prime genetically susceptible individuals to develop celiac in response to gluten.

Dr. Fasano's group has also published a study showing that bacteria such as E. coli and Salmonella stimulate zonulin production in isolated intestinal tissue, and another recent study showed that short-term inoculation of rats with E. coli and Shigella enhanced the ability of gluten to cause intestinal damage while inoculation with Bifidus bacteria virtually eliminated gluten's ability to cause damage.  Neither of these studies show that dysbiosis contributes to celiac, or that it is responsible for the persistence of zonulin production on a gluten-free diet, but they offer strong support to the plausibility of these hypotheses.

In any case, it is true that Dr. Fasano's 2006 study showed that gluten was capable of increasing zonulin and consequently increasing gut permeability ex vivo in intestinal tissue from both celiac and non-celiac subjects.  Still, the effect in tissue taken from non-celiac individuals is pretty small.

Here's the effect on zonulin:

Here they show that in the mucosal layer, but not the serosal layer, zonulin increases in response to gluten ex vivo, but that zonulin concentrations are dramatically higher in celiacs to begin with and remain dramatically lower in non-celiacs at all time points.  

The mucosal layer is more superficial whereas the serosal layer is more deep.

Similar results were also seen for TEER, their estimation of gut integrity:

Here again we see that although gluten decreased gut integrity even in tissue isolated from subjects without celiac who were eating gluten as part of their normal diet, it never declined even close to the level seen in celiacs who had been gluten-free for two years.

As I pointed out in my last gluten post, these ex vivo experimental results showing that gluten proteins increase zonulin and leaky gut in isolated intestinal tissues cannot logically be construed as evidence that gluten causes leaky gut in live humans without celiac disease.  There are far too many factors that could intervene in a live human to change the result.  And indeed, Dr. Fasano's most recent study showing that people with non-celiac gluten sensitivity do not have leaky gut and the Australian study showing that gluten does not cause leaky gut in such individuals directly refute this concept. 

Whether gluten contributes to the leaky gut seen in other diseases such as autism remains to be seen, but based on this data, one could could suggest that this is the case as a plausible hypothesis.

Ultimately, however, the most remarkable finding of this study is the massive persistence of zonulin production and leaky gut in celiacs even after they have been gluten-free for two years.  The authors noted this in their conclusion:
Nevertheless, zonulin is markedly up-regulated in subjects affected by [celiac disease], even when treated with a gluten-free diet.  This up-regulation is associated with increased baseline gut permeability, and an increased amplitude and duration of gluten-induced zonulin release when compared with non-[celiac disease] intestinal samples.  Despite the presence of measurable zonulin response in both [celiac disease] and non-[celiac disease] subjects, [celiac disease] patients appear to reach a critical threshold of intestinal permeability upon gliadin exposure that is not reached in non-[celiac disease] intestinal mucosa.
This is remarkable because it suggests that celiac is about more than just genes and gluten.  I will revisit this topic when I get my food toxins and food intolerances series going.  In the mean time, I owe you all a sequel to my last LDL post, and  then it'll be back to fructose for a while.

Read more about the author, Chris Masterjohn, PhD, here.


  1. Interesting! I sure would like to know the whole story.

    One hypotheses to consider would be whether or not their purported gluten-free diet truly was gluten free. Unless they had a test to ensure that the subjects didn't get any contamination then we can't say for sure that it was gluten-free. Wheat gives me a rash and so does barley-fed beef. Grass fed beef does not, so I assume that it is some (not neccessarily gluten) component of gluten-grains.

    I'm getting a celiac test soon to know for sure what my status is. I just know that I get rashes from gluten grains and some other adverse effects.

    Just some anecdotes for ya to help get the brain going. This is a treat to read. Keep it up!

  2. "... it may be that certain types of intestinal dysbiosis (improper balance of bacteria and yeasts in the intestines) prime genetically susceptible individuals to develop celiac in response to gluten."

    That sounds highly plausible.

    I was interested to see in the New York Times recently that the condition is on the increase and - I quote from memory - "appearing in people who've eaten gluten with no problem for 70 years".

    I wonder if factors that could disrupt gut flora are also on the increase.

    It's certainly a huge area whether involved here or not. I read in the Times (of London) recently that antibiotic use is now thought to be the culprit in one of the hospital superbugs. Essentially it takes advantage of the tabula rasa of an antibiotically cleaned system to establish itself. The doctor reporting this for the Times tells readers not to gag and adds that there's been some success treating it by inserting bacteria from a healthy person's faeces directly into a victim's stomach.

    I'm also told by a friend in natural History that vultures in Spain are now thought to be dying out on account of antibiotic use. They pick up the carcases of dead farm animals and if those have been treated with antibiotics by the farmer the vulture's gut flora can get disrupted.

    1. If celiac disease can hit individuals who have lived decades tolerating gluten, shouldn't we question the idea that celiacs are genetically pre-disposed? Maybe all are, maybe most, maybe none - the decisive processes may be epigenetic.

  3. As Paul Jaminet would say: "it's the chronic infection, moron!" (ok, excluding the "moron" part! ;o))

  4. As you note, this is pretty dramatic stuff and leads to a number of plausible hypotheses implicating something other than gluten (and genes) in celiac.

    I wonder if the lady we once knew as the "glutenator" on the native nutrition list follows your blog. She goes by a different name in the blogosphere these days otherwise I would mention her name directly. :-)

  5. Interesting post. I agree that zonulin should be a target for a lot more research (both in coeliac disease and a few other GI conditions also). The gut bacteria/dysbiosis story is a complicated field with lots and lots and lots of different interfering factors outside of just diet, meds, genetics, etc. Emily at EP blogged recently about behaviour (stress) affecting GI bacterial populations (in mice) and Neurophilosophy blogged about GI bacteria affecting behaviour (again in mice). A sort of bi-directional relationship between gut bacteria and behaviour (at least in mice). Added to this, recent preliminary work suggests that going on a GF diet in non-coeliac might actually be part of the problem in terms of what the GF diet does to 'good' and 'bad' bacterial populations: http://www.ncbi.nlm.nih.gov/pubmed/21327021
    (although this is slightly different from what I have heard previously about GI bacterial composition and different forms of diet).
    It's a complicated world in them there guts!

  6. Michael I'm wondering why you wonder if the Glutenator is following Chris' blog? If you think these studies would change her approach to diet, I think you're wrong. Like many of us who have discovered restored health by leaving gluten and casein off our plates, these studies are interesting, but certainly not deal-breakers when it comes to how we live and eat. We know what works for us and THAT evidence carries far more weight than any scientific study. What I wonder is how these studies find enough truly gluten-intolerant individuals (and how do they conclude that they are or aren't gluten-intolerant?) who have been completely gluten-free (and how do they confirm that they truly have eliminated ALL gluten?) that are willing to ingest any amount of gluten in order to participate in a study make it viable. No amount of money would be worth that nightmare to the truly gluten-intolerant. And that fact alone leaves doubt in my mind that the conclusions from any of these types of studies are completely accurate. Indeed there is a lot to be discovered on this topic, but this study and others like it are far from conclusive. I'll continue my gluten-free diet, thank you very much, and I have no doubt but that the Glutenator will as well.

    1. How can you find a strictly gluten-free person that is willing to eat gluten (suffering the consequences)for a study? Get moms, like me, who are diagnosed Celiacs with children whom also have it. We are glad to go through anything to save our children. But yeah, as soon as the study is done, back to gluten-free. This doesn't mean I think I am cured though just being gluten-free...we need to know more, just think about the possibilities, if we found what causes the increased Zonulin, maybe we could prevent or treat several auto-immune diseases.

    2. No one ate gluten for this study. The study is EX VIVO which means, literally, "out of the living" i.e. not in your body. Cells were tested in a laboratory. Why don't you read Chris' previous blog, referred to in the first line of this article, which explains this clearly?

  7. Interesting, and as you and others have noted, the possibility of some other element triggering zonulin production does seem highly plausible. After all, isn't this what the GFCF diet is all about and, taken a step further, by removal of all possible issues with gut dysbiosis due to impaired digestion of all polysaccharides, Campbell-McBride's GAPS diet? As Paul points out, it's definitely a complex world in those guts of ours :)

  8. This is a very interesting post, thank you very much. I'll follow what'll be coming next here!

  9. I think the guts microbiota is the key......and always has been the key. Nice job Chris bring this to our conscious streaming
    Dr. K

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  11. If this is a duplicate, I apologize, my computer locked up when I was trying to comment. Here is an interesting article where Fasano hints at gut flora as well:
    Also iteresting is that before gluten discovery, the official celiac diet used was the Haas Specific Carbohydrate diet (now known as the SCD). As early as the 1920's Dr. Sidney Haas suspected that undigested starchy carbs were being used by the wrong bacteria to cause the disease and that by removing those carbs for a year or more starved them out and cured the patient. Also interesting is that he, and other doctors using the diet during this time noted odd behavior in the more severe patients and that behavior cleared up on their diets. There is an except from the book here: http://breakingtheviciouscycle.info/autism/dr_hass_exerpt.htm
    the book, published in the early 1950's, has been republished and is very interesting.

  12. Hey Chris, incase you don't know...http://www.westonaprice.org/health-issues/2162-nonalcoholic-fatty-liver-disease

    They have a nice RSS for the journal now.

  13. Chris, what do you think of this study?

    Mrs Ed: I got it from your site. Thanks. You have an awesome site!

  14. I'm glad you're writing about Fasano's zonulin papers, I was interested in them but didn't have the time to read them carefully. I think Robb Wolf (I do love the guy) is misinterpreting Fasano's work.
    The low zonulin levels in non-celiacs doesn't mean wheat is safe and healthy for all non-celiacs, though. I wonder how wheat consumption impacts gut flora, and I wonder about the opioid-like fragments in wheat, and wheat's other chemical defenses.

  15. All this makes me wonder what's going on in sourdough. I've read many posts from gluten sensitive people who can eat sourdough. I'm guessing a lot more than gluten reduction is going on. Perhaps some of the end products produce their own effects.

    Gluten content in wheat has been on the rise (no pun intended). Baker demand has motivated wheat breeders to up the gluten content. Plus bakers can added gluten sine it is available separately.

    1. sourdough has probiotics

  16. This whole story is starting to sound a lot like the carbohydrate --> insulin --> insulin resistance hypothesis, from which there seems to be a missing component, likely leptin resistance in the hypothalamus. It makes me wonder if the disregulation of zonulin has a similar hormonal resistance in the brain as a causal agent.

  17. http://somvweb.som.umaryland.edu/absolutenm/articlefiles/1445-Zonulin%20and%20Its%20Regulation%20of%20Intestinal%20Barrier%20Function,%20Physiol%20Rev%202011.pdf

    Here is Fasano's 2011 article that takes the gloves off and claims that this mechanism is behind all autoimmune disease, inflammation diseases and many cancers. It is a goldmine!

    1. The link is invalid as of 08-09-14. Do you know of another way to get this paper?

  18. Chron's Dad, wow what a paper.

    I don't know if it's good or bad but Fasano's company is developing that zonulin-inhibiting drug for market. The paper looks sort-of like a fishing trip for applications for the drug.


    In any case, I would love to see Chris do a summary of this Fasano paper.

  19. Awesome tear down of the study, I agree the most significant and interesting point is that the Celaic's had such a high amount of zonulin production. I think as you suggested this is do to dysbiosis including bacterial, yeast but also parasites. I think that is a huge missing piece that is often overlooked because it's too hard to measure and define at this point.

    Regardless I don't think the new zonulin drugs are going to help the situation at all, in fact I think they are going to end up hurting the uneducated population treating a symptom not a problem just like PPI's for GERD.

  20. I agree with Steve SCD about the possible new drugs to some extent. I'm a male who had to pay for Lotronex to take it when first put on the market before removal and it did stop my Diahrrea. It was removed initially because it caused some folks to experience dead sections of their gut. The Lotronex according to what I have read lately did block the excess zonulin that opens the TJ cells and causes the leaky problem. Hopefully the newer drugs can be controlled closer on dosage and still block the zonulin without causing damage or even death.

  21. In his lecture (http://www.youtube.com/watch?v=pfhJeV-qhjA), Loren Cordain says grain & legume lectin's (ie WGA) bind with milk & bacterial proteins and then cross the gut barrier via the EGF Receptor. In addition, lectins acts as adjuvants and get the immune system to create antibodies to the lectin bound proteins. What do you think?

  22. I would be interested to know what the celiacs were actually eating during these tests/trials. For almost 3 years, I have thought that I was on a GF diet, eating GF breads, using rice flour in baking etc. However, my bowel problems continued until I removed most grains from my diet. Through a process of trial and error, I have discovered that the majority of so called GF products, flours etc are in fact cross-contaminated with gluten. The only grain I can eat and be certain it is GF, is brown rice and flour that I grind myself from whole brown rice.

    1. I have read the book "Breaking the Vicous Cycle" When you follow a gluten free diet many of the foods have high amounts of starch that feed a "klebsiella bacteria" in the stomach. When. I looked up that bacteria on the internet, I was surprised at the answer. Another good article is "Of Microbes and Men" I have recently food that the inflammation factor for one cup of brown rice is -598 and used to make a banana bread with two cups. I did not add up the rest of the ingredients. I am currently looking for a flour to use that has close to a zero inflammation factor.

    2. I have now gone completely grain free and use lentils a lot. I grind them into flour and have baked lots of yummy things with it. You can also make a mix with buckwheat flour and lentil four. There are endless possibilites out there. I am now tending to think that grains, period, are the problem for some of us. I'm now on a vegetarian diet, grain and dairy free and feel amazing.

    3. Anonymous -- lentils have high levels of saponins and phytates -- some say they're worse than other grains. And by the way, brown rice decreases inflammation, based on clinical studies.

  23. Hi Anonymous,

    Yes, that is a potential problem. However, the fact stands that in most studies that make an attempt to rigorously rule out trace gluten consumption, they find that in the majority of the patients the small intestinal pathology is not healed on a GF diet. While this may mean that it is just so extremely difficult to be truly GF that it is hardly ever achieved, it may also mean that the primary cause of small intestinal pathology in celiac disease is not gluten. After all, what is the evidence that it is gluten if you cannot cause celiac simply by adding gluten to a diet and you cannot heal celiac simply by removing it?


  24. Hi Chris. Thanks so much for responding! I was about to suggest that it might all be to do with genes, but upon further research it would appear that the prescence of HLA DQ 2 or DQ8 does not always mean celiac disease. This is all so frustrating, especially when one just wants to heal.

    Kindest regards

  25. Hello Chris,

    I would like to see people with ulcerative colitis and crohn's disease as the controls. What amount of zonulin do they make? They took perfectly healthy people and compared them to celiacs, which is great. Now let's take other people with gut problems and see if they product zonulin and see if it is a problem further down the gut. There is also the problem that some celiacs may not know they are eating gluten. Our food is changed so much, that sometimes the FDA determines they don't need to tell the public about these changes. Pink slime is an example of this. What are they adding to food that celiacs don't know about? Could there be gluten sources that are small and don't need labeling? Additives and such that have small amounts of gluten that may cause zonulin problems for cealiacs? I'm not sure and I'm not an expert on evolutionary biochemistry of the gut. So many questions. Great post. Thanks for explaining the results of this theory. Very much appreciated.

    Best Regards

  26. This is very interesting. However, it doesn't apply to me.

    I have non-celiac gluten sensitivity, but I also have pretty clear signs of intestinal permeability.

    As I used to believe I had celiac, I went to two gastroenterologists in recent years. One of them performed a duodenal biopsy which came out absolutely normal. Later, I paid for a genetic analysis which was negative on HLA DQ2 and DQ8. Blood tests on the usual celiac parameters were negative.

    I was, however, positive on IgG antibodies against wheat and some other things. I also had a moderate amount of gluten and casein peptides in my urine.

    I had psoriasis since 1997, but my milk and gluten intolerance trouble only became severe from about 2003/04. First, mental symptoms dominated, but in recent years it is much more somatic. From 2007 onwards I got severe fatigue and some hair loss.

    My last gluten challenge was in 2010, and since then I have been strictly gluten-free and milk-free, only interrupted by 'glutenizing' accidents. My reactions are pretty severe, and will be provoked by just a few milligrams of gluten (I base this on experiences with the gluten amount in wheat starch and some beers which are branded gluten-free, but still contain some gluten - e.g. 6 ppm). Contrary to most celiacs, I get almost no gastrointestinal symptoms, but strong reactions in the rest of the body: joint pain, muscle pain, headache, fatigue, some influence on personality, 'autistic' feeling, tinnitus, strong neuropathic stinging pain ind feet and hands, itching and other things.

    And the the intestinal permeability.

    During the last 2-3 years this has gotten worse, despite my diet. When eating certain amounts of sugar or starch, I quickly get tingling and some pain in feet and hands, cold fingers, and even a slight numbness around the lips, tinnitus, and an allover hangover feeling.

    Antifungals always help - but after the course of treatment, symptoms come back. So I am pretty sure that fungus has to do with it. It is entirely possible that my gluten and casein intolerance is secondary to a yeast overgrowth and gut dysbiosis. Because the surface of gliadin and casein molecules is quite similar to candida, so your immune system will develop cross-reactions. I think the cause of my neuropathic symptoms is that these food molecules - or candida molecules - leak from the intestine into the bloodstream and provoke an immune reaction. The antibodies will then possibly attack my neurons or myelin too.

    My current situation is that I just ended a cause of fluconazol - which helped - but symptoms are coming back. Maybe I should have my zonulin tested. However, if it comes out that I do not have increased gut permeability, I would wonder very much what the cause of the neuropathy could be.

    1. You have all the signs and symptoms of SIBO or Small Intestine Bacterial Overgrowth. It's the Small Intestinal Dysbiosis that is making you react to grains. You can diagnose this only with a Breath Test for Methane and Hydrogen gases. Check it out on the web for a lab in your area. In Australia Stream Diagnostics does this test.
      Hope you find the road to recovery

    2. C, I read your post with widening eyes, since I have developed very similar symptoms in the past decade or so. From a fit and youthful 52-er, albeit with a lifelong intolerance to too much wheat, I've become a creaky old 62-er.

      But there's more....

      Two weeks ago, feeling like my body was really falling apart, I went to see a German "Heilpraktiker" whom I've consulted before. One of the diagnostic tests was for food sensitivity.

      The results are startling. Top of the "danger" list are goat's milk and ewe's milk and their cheeses, milks I had switched to in 2006 after an initial food sensitivity test had revealed cow's milk to be a problem. The latest test showed cow's milk to be relatively benign, but lamb, chicken and beef are a big no-no. All, yes ALL of the current "danger" foods are the ones I've consumed most of, regularly, for several years, and have done so precisely because according to the earlier test they were all safe. And the foods the earlier test had flagged as problematic, which I've consistently avoided, are now OK or at best a mild risk!

      So what does this tell us? Do these haywire food sensitivity tests just show how useless they are? That was my first thought, I admit. Then the truth dawned: this is pretty clear evidence of leaky gut - my body is reacting to WHATEVER foods I consume in any quantity.

      Confirmation arrived 2 days later in a report from a different lab. Biomarker tests on another blood sample revealed, among other things, significant inflammation of the intestinal mucosa.

      Treatment is underway, watch this space...

    3. I'm sorry you've had to deal with all that! Your symptoms sound like what I went through. Mine not as severe. I bought a glucose meter, on the suggestion of a co-worker. I tested my blood glucose when I started to feel my symptoms return even though I knew I had been GF. And I discovered that high blood glucose gave me the same symptoms, so now I also am very careful with my glycemic level along with staying GF. It has helped. Good Luck

    4. Getting back to my comment above (of September 3, 2012 at 3:47 PM):

      This spring I tried to do a zonulin provocation test. I took a baseline blood test (gluten-free and milk-free diet), and another test after 24 h with sugary food, and a third test 2 hours after eating gluten.

      The results didn't show any clear reaction:

      Base value (gluten free, milk free, healthy diet)
      zonulin 23,9 ng/ml

      Next day, after sugary and starchy foods for 24 hours:
      19,7 ng/ml

      And later same day, 2 hours after gluten intake:
      25,0 ng/ml

      The lab mixed up the results at first, but later they claimed they had recorded the text I wrote on the tubes, so the results I mention here should be the correct version, although not without a slight doubt. The lab agreed I shouldn't pay, although they insist these figures are now correct.

      But anyway, if the zonulin level rose after eating gluten, it was only slightly. From 19,7 to 25.

      While zonulin is released within minutes when you measure gut cells in a test tube, it probably takes some more time to enter the bloodstream in a significant amount.

      So two weeks ago I tried again. Now I ate gluten and milk for 15 days, prior to a neurological examination. (Skin biopsy on suspicion of small-fibre neuropathy. Result not in yet).

      After 15 days on gluten + milk
      zonulin 35.4 ng/ml

      So the value has risen significantly.

      The reference level of this particular laboratory is <38, that means normal or average people should have under 38 ng zonulin per ml serum. (But reference levels don't guarantee what a 'healthy' limit is.)

      However, this sounds like a very high reference level.

      I found a German study also measuring in ng/ml serum.


      They found that ALL of 80 psoriasis patients had zonulin below the detectable limit (8.6 ng/ml), and all but 4 of 80 healthy controls also had zonulin below that limit. Among the last four one had 39 and the other three had very high levels over 300.

      Fasano's studies measure it in ng zonulin per mg serum protein.

      I am not entirely sure how to convert this, but I have found out that blood serum usually contains 6-8 mg protein per ml. So I assume that you can divide the German ng/ml number by 7, and then you get the American zonulin ng/mg.

      So the reference value of the German lab, 38 ng/ml, would be translatable to 5.4 ng/mg.

      Now, if you compare this to the numbers mentioned in the blogpost on this page, and in medical articles, the German lab reference value is very high. It is also very high compared to the German psoriasis article (link above). So I need to check up on this.

      What I can conclude is that my zonulin did not react clearly to a one-time gluten meal, at least not at the test time 2 hours later, but it did react to 15 days of gluten provocation.

      This might have been different years ago, when my intestines were worse. I had a slow but steady improvement since my antifungal course last year in August. I am still not sure whether gluten, bacteria or fungus is the root of the problem. I'll try and get some other gluten tests now.

    5. It is now Oct of 2014 and your message is still helping others. Thanks to Chris for publishing this article and to the people who have responded. I have Celiac and have been gluten free for 20 months however I do get glutened accidentally and every time my symptoms come back with strength and severity. There are times when I feel so overwhelmed by my inability to be totally gluten free and lead a normal life that I feel like I can't take it any more. This information, though several years old has gotten me what I feel is a step closer to beating this disease. Thanks so much.

  27. Hi C,

    I am also non-celiac gluten sensitive, with many of the same symptoms.

    My fist though when I read "...cannot logically be construed as evidence that gluten causes leaky gut in live humans without celiac disease." was the same as yours- researchers should be testing those with non-celiac autoimmune symptoms (hashimoto's, RA, BiPolar, lichen schlerosis, etc) as well as those healthy individuals to get a lear picture of the role of zonulin.

    I'm so happy that this disease is finally being taken seriously-- I suffered for years before I figured out gluten was a problem-- hopefully this will save others from the same fate.


  28. Maybe GM food has changed the DNA of the gut cells, so that the gut cells are producing toxic fungi. That could be why antifungals help during the treatment, but symptoms come back later.

  29. Anybody know if poo transplants from healthy individuals help celiacs? Could it be that excess zonulin production is an attempt to absorb certain nutrients lacking in the diet? I have occasionally wondered if the effect of zonulin is how the human gut absorbs iodine. Where else is zonulin found in nature?

  30. DogtorJ is a blog by a healed celiac. He says that most celiacs do not heal because they continue to eat foods that affect their gut. He healed his celiac's by totally eliminating wheat/gluten, dairy, soy, and corn. He says that even small amounts of contra-indicated foods will prevent healing, and that many people inadvertently do this. So it would have been interesting to measure zonulin from celiacs eating a paleo, dairy-free diet.

  31. With the removal of gluten and toxins from my diet, I have alleviated a long list of symptoms that contributed to chronic insomnia. If I had not stumbled on to the idea of going gluten free at precisely the right time, I would now be taking SSRI's and Parkinson medication for PLMD at 98%.

    Thank you so much for this information. I am trying to learn all I can about how gluten affects the brain.

    I am now experiencing life with less anxiety, and in time, I expect to be able to attach a name to my comments........lol.

  32. From your main text and indeed many of the comments above, the first thing I thought was "I wonder if fecal transplants could have a role here?". Thoughts?

  33. This comment has been removed by the author.

  34. You may want to take a look at this study - http://archive.hshsl.umaryland.edu/bitstream/10713/2431/1/Follow%20up%20study%20Deb%204-25-05..pdf

    It demonstrates that patients with celiac disease, after 17 months on a gluten free diet, for the most part have normalized levels of zonulin. This would suggest that the root cause of the leaky gut is indeed gluten.

    1. Thanks. That does loosely support that a GFD reduces zonulin, though it would be much more powerful support if the study had been randomized and controlled. However, the comparison is apples and oranges in some respects, because this just shows that zonulin goes down, not that it goes down to the level of healthy controls. I don't know why this is a mostly pictorial description of the study in comic sans point -- is the full text somewhere? -- but it is not clear how they determined 7 out of 53 were non-compliant, nor why out of 46 compliant patients serum zonulin is only shown for five, unless only five of those 46 had improved zonulin. That would seem to suggest that the GFD is not all that effective in the majority of celiacs in normalizing zonulin.


  35. It's possible that the gf celiac subjects have multiple undiagnosed intolerances. There's no carved in stone rule that only gluten causes a problem. In fact I've seen that soy and maize also cause villious atrophy.I react way worse to buckwheat (gastritis and ulcers)than gluten (fatigue and mild IBS).

    I wonder if anyone has tried helminthic therapy for celiacs. Bit of a tangent I know, but I know it works for Crohn's, and there's evidence from Brazil that it affects MS as well. Knowing now that there's a genetic link between these conditions, I wonder if the worms suppress the zonulin in the gut somehow. Just a thought.

    I also wonder if prior use of antibiotics is disturbing the flora enough to trigger or worsen gluten intolerance.

  36. Heloma molles typically develop between the fourth and fifth toes when one of the toe bones (phalanges) is slightly too wide. Normal phalanges are hourglass-shaped and the tips are wider than the middle.

  37. These are interesting findings - I would be cautious about making inferences relating to the 'gluten free' study population (celiacs) because it's almost impossible to obtain a truly gluten free diet. There is plenty of research (both old, eg looking at evoked potentials in a diet with an without gluten; and new, eg the neurological effects of gluten on the immune system) to suggest that there will still be measurable differences in celiac and non celiac populations unless the celiacs are eating a truly zero gluten diet (not the 20ppm or more that is currently used in assays).

  38. Whoa this is a brilliant breakdown. (Love the graphs.)

    "... these ex vivo experimental results showing that gluten proteins increase zonulin and leaky gut in isolated intestinal tissues cannot logically be construed as evidence that gluten causes leaky gut in live humans without celiac disease."

    With all the very intelligent alarmists out there it's nice to have some critical thinking non-alarmists out there too :)

  39. The author of this blog seems to have missed the whole point of Fasano;s study, which was not to demonstrate that gluten intake leads to higher level of zonulin but, on the contrary, that high levels of zonulin (endemic to certain individuals) lead to gluten sensitivity because zonulin permits gluten to pass through the intestinal lining, which can then trigger the autoimmune reaction, celiac's disease.

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  47. My own personal experience has taught me that "gluten-free" diets can still cause a lot of problems. Gluten is a prolamin. I've had to go on a prolamin-free (grain-free) diet. I suspect that many people have prolamin intolerance, and go on "gluten-free" diets and continue to have problems. This implications for this research is that the test subjects "being on a gluten-free diet for two years" were likely still consuming prolamins. This could have an adverse impact on the study. It would be interesting to see the same study using "grain-free"/"prolamin-free" celiac subjects.

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