10 years later, my celiac is progressing

[trents]

10 minutes ago, GardeningForHealth said:

This sounds quite similar to my situation. 

A hypothesis: perhaps the original gut dysbiosis that caused our celiac disease, does not get repaired over time with the gluten-free diet. Perhaps our guts remain in some state of dysbiosis, and this over time causes increasing sensitivities to food antigens despite the gluten-free diet.

This strikes me a being a likely explanation or a big part of the puzzle at least. To look at it from another angle, the dysfunction of our immune system with regard to misidentifying food proteins as threats starts with gluten and can expand over time to include the proteins in other common foods. In other words, this slice of the immune system function becomes increasingly dysfunctional over time.

[Scott Adams]

17 hours ago, Jeff Platt said:

I was diagnosed at age 49 with a blood test, became completely faithful at a gluten free diet and am even sensitive to cross contamination and pots and pans that have cooked gluten before. I have been glutened a hand full of times this past decade but am faithfully observant. I am currently at a gastroenterologist and functional MD trying to find out why I am still having issues even though I’m off so many other foods, dairy, some fruits, and some  brands of rice. But I seem to progressively be getting a little worse or maybe just returning to the same symptoms I had originally, though no where near as bad as I was before stopping gluten. It feels like I take two steps forward and then one step backwards every time I stop another food. I don’t know where this rabbit hole is leading me but am hopeful both can find out why. 

This article may be helpful:

 

[trents]

Also, I'm pretty sure zonulin has been identified by researchers as the enzymatic protein that regulates epithelial matrix opening size in the villous lining. The challenge is understanding how to regulate zonulin levels. If someone gets that figured out it would likely be a breakthrough for the celiac community.

[knitty kitty]

Histamine plays a big role in gut dysbiosis.  Zonulin is a downstream effect of histamine and inflammation.

Food Intolerance: The Role of Histamine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469513/

Food, gut barrier dysfunction, and related diseases: A new target for future individualized disease prevention and management

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10084985/

P.S.  Ask for an Erythrocyte Transketolase test which is more accurate than blood level tests.  

Edited June 6 by knitty kitty
Added post script

[Scott Adams]

On 6/6/2024 at 9:39 AM, trents said:

Also, I'm pretty sure zonulin has been identified by researchers as the enzymatic protein that regulates epithelial matrix opening size in the villous lining. The challenge is understanding how to regulate zonulin levels. If someone gets that figured out it would likely be a breakthrough for the celiac community.

There is some interesting research that hope continues which indicates that zonulin serum levels may one day help diagnose NCGS:

 

[GardeningForHealth]

On 6/6/2024 at 11:39 AM, trents said:

Also, I'm pretty sure zonulin has been identified by researchers as the enzymatic protein that regulates epithelial matrix opening size in the villous lining. The challenge is understanding how to regulate zonulin levels. If someone gets that figured out it would likely be a breakthrough for the celiac community.

Dr. Fasano states in this video, starting at 22:50...

...that before zonulin levels become elevated, the gut is in a state of dysbiosis. So dysbiosis comes first and causes the zonulin levels to rise which then a few months later leads to Celiac Disease. To me, this sounds like zonulin is not the culprit, but rather the gut dysbiosis. And so, this leads to the next obvious question: In the development of Celiac Disease, why does the gut dysbiosis occur / what is causing that? 

Another question I had when watching this video, from 17:20 to 20:00, is that, Dr Fasano says that there are solutions available for Celiac people who are not responding to the gluten-free diet that can be implemented to "get them by" until a non-diet therapy emerges from the various clinical trials and receives FDA approval. But he does not indicate what those "solutions" are, besides avoiding cross-contamination. He seems to indicate that there are solutions, but does not go into what these may be, and I would like to know.

[trents]

But one big variable in all of this is I think that no one knows how to objectively define what a healthy gut biome is. So, if you can't define what it is, you don't have an objective target for restoration. And even if zonulin levels aren't the genesis of the problem, it apparently is what is immediately responsible for the leaky gut. So, figuring out how to regulate zonulin levels would still seem to have therapeutic promise.

[GardeningForHealth]

1 hour ago, trents said:

But one big variable in all of this is I think that no one knows how to objectively define what a healthy gut biome is. So, if you can't define what it is, you don't have an objective target for restoration. And even if zonulin levels aren't the genesis of the problem, it apparently is what is immediately responsible for the leaky gut. So, figuring out how to regulate zonulin levels would still seem to have therapeutic promise.

Dr. Fasano speaks about microbiome "profiles." He has made distinctions between unhealthy profiles vs healthy profiles. I would be interested to know the answer within the context of Dr. Fasano's CDGEMM study. For example, of the study participants who did not develop high levels of zonulin, how did their microbiome profile differ from the ones that did develop high levels of zonulin? We could then say that those who did not develop high levels of zonulin had healthy microbiome profiles.

And then this would lead back to the question: what caused the gut dysbiosis in those who developed high levels of zonulin?

[trents]

But there are other questions. How does gut dysbiosis correlate with the presence or absence of HLDQ2 and HLDQ8 genes? Are those with the so-called celiac genes more prone to develop gut dysbiosis? Are the zonulin levels of those with the celiac genes impacted to a greater degree by gut dysbiosis than those without the celiac genes? I'm not sure Fasano has really nailed down the answer to the chicken or the egg question.

Edited June 8 by trents

[knitty kitty]

High carbohydrate diets contribute to gut dysbiosis.  

When we consume diets that are heavy in carbohydrates, excess carbohydrates don't get thoroughly digested.  The bacteria in our guts ferment the carbs (resulting in gas and bloating).  This can allow carbohydrate loving bacteria to out-populate the beneficial bacteria in our guts, resulting in dysbiosis.  Add to that high fructose corn syrup, used as sweeteners in many carbohydrates, which forms a matrix which can be used by colonic bacteria to climb into the small intestine and colonize there.  

High carbohydrate diets require additional thiamine to process the high carbohydrate load.  Additional Thiamine is needed to keep those intestinal bacteria controlled.  Thiamine is also needed to calm mast cells so less histamine is released.  

Hiding in Plain Sight:  Modern Thiamine Deficiency

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533683/

 

[GardeningForHealth]

Well guys, you know what they say about those who assume. I was assuming that my diet was free from all exposures to gluten, but I am now re-evaluating this assumption, because it may in fact be wrong, in light of this post:

Thankfully I never did buy any of the foods on Mom's Across America's list of gluten-containing "gluten-free" foods. However, what about my supplements? I did a trial of stopping all supplements for 30 days. Today is Day 17 so far, and I am feeling better. My supplements are all labeled "gluten-free"--but how much can I trust that label? 

The answer is, not much! Turns out, having the phrase "gluten-free" on the product packaging doesn't mean much, as per the FDA's website; under the Compliance section, where you will see this: 

Are manufacturers required to test for gluten to make a “gluten-free” claim on their food labels?

No.

Well, that was a reality check right there.

I called the supplement company today to ask them if they test for gluten and their answer was, "No, but our products are gluten-free." I then asked them, "If you don't test, then how do you know?" And they said that their suppliers are doing gluten-testing. I told them that wasn't sufficient; they should be doing their own testing on their finished products.

Its a shame that we cannot trust the phrase "gluten-free" on the packaging.

[trents]

Correct. Most people make the assumption that if a food item bears the label "Gluten Free" it has been tested and proven to be such. But the reality is the companies are not required to do so and many will not until they are forced to by consumer complaints about being glutened and attorneys get involved. Up until the recent revelations connected with MOA's testing, we could place much more confidence in "Certified Gluten Free" because we knew that some actual testing had been done on all certified gluten-free products. But now we know, apparently not frequently enough.

Edited August 5 by trents

[GardeningForHealth]

Well it really shocked me because for the past few years I had been operating under the assumption that ever since the FDA came up with their 20ppm rule, that that came with legally required testing on any product that carried a "gluten-free" label of any kind. Now I know that this is false, just shocking and disappointing. That 20ppm rule should have come with some teeth. It is too burdensome for a consumer to sift through and try to figure out which labels are trustworthy and which ones are not.

[trents]

The reality of all this may turn out to be that most of us are getting more gluten in our diet than we realized, despite being very conscientious. This would go a long way in explaining why so many see improvement but whose follow-up test scores point to some gluten still getting in there somewhere, despite their extreme caution. It may also explain some "super sensitive" experiences who are already close to the reaction threshold from eating "gluten free" products that weren't tested and really don't meet the standard. We must keep in mind that it's not always the amount of gluten found in one item that can trigger a reaction but the total amount ingested over a 24 hr. period. In fact, the FDA's 20ppm guideline is based on the amount consumed over a 24 hr. period for the typical total calorie intake over that time. At least that's my understanding.

[GardeningForHealth]

I am really starting to see that things are not where they need to be for Celiacs and gluten-sensitive people. My sister, who years ago tested positive for Celiac and had a positive endoscopy to confirm, just recently tested mild positive for Celiac again, after being on the gluten-free diet and having negative blood labs for many years.

Her recent test result was: Tissue Transglutaminase Ab, IgG: 8 U/mL (ref range: 0-5 normal, 6-8 weak positive, >9 positive).

This means she is getting exposures in her diet more recently, whereas in the past she was not getting these exposures. 

Furthermore, I only just recently found out about the difference between "gluten-free" and "certified gluten-free," and that we are supposed to be able to trust the certified products more--but then this Moms Across America story comes out. I've downloaded their lab results from their website and I see that several brands that tested positive are certified gluten-free. How did the certification program miss these products?

This shakes my confidence in the gluten-free certification programs. How can we trust that the food we eat is safe? 

[trents]

It is clear to me that testing standards and protocols are much too relaxed in the gluten free/certified gluten free food sector. It's somewhat of a crap shoot for us who are dependent on them. I'm beginning to wonder if the label "Gluten Free" actually carries any more benefit than using mainline food products that don't list wheat/barley/rye as an ingredient irregardless of cross contamination considerations.

[Scott Adams]

What is most disturbing to me is that the GFCO is not reacting in a normal manner to the lab results found in the Moms Across America study, and have come out with a blanket denial, even though the lab that did the testing has offered to allow them to run tests on their samples. We'll be doing another article on this shortly. Interestingly, the GFCO isn't doing these tests directly--all of the follow up tests have been done by "independent" labs that are contracted by the certified companies. It seems like some random sampling should be done by the GFCO directly.

[GardeningForHealth]

From their denial statement: "We asked the manufacturers to run multiple tests on their retained samples from the lots named in the MAA report."

Why didn't GFCO do their own testing, instead of asking the manufacturers to re-run tests? I thought that GFCO was more of a "watchdog" pro-consumer organization who did their own independent testing. Another false assumption?

Their website states: "GFCO operates an independent, third-party certification program for gluten-free products." I had initially translated this to mean that GFCO does its own testing using its own independent laboratory, but now its looking like this is not correct. I can't find any info on their website that explains how their program actually works.

The model of food manufacturers contracting with laboratories to conduct food safety testing is is an imperfect model because the labs are financially incentivized to produce passing lab results for the manufacturers.

 

[Scott Adams]

You are correct, and the companies who are certified by the GFCO contract their own "independent" labs to do all of the testing for certificaiton, and I don't believe that the GFCO does their own testing, monitoring, etc. Here is the info we could find on their program: https://gfco.org/wp-content/uploads/2024/05/GFCO-Manual.pdf 

It is unclear if there is a certain lab or group of labs that the companies must use to do this testing, but it looks like it is up to the companies themselves to contract them for this and run all tests, then report the results to the GFCO.

[Scott Adams]

On page 26 of: https://gfco.org/wp-content/uploads/2024/05/GFCO-Manual.pdf 

Quote

Testing Methods, Documentation and Submission Testing can only be done using test kits found on the GFCO Approved Kit list. Alternatively, the plant may choose to have testing done by an outside lab that is accredited to ISO 17025 for gluten testing, again using a GFCO-approved method. In either case, test results should be completed and reviewed prior to the release/sale of certified Product.

So companies can perform the tests themselves, and not use any independent lab at all.

[GardeningForHealth]

5 minutes ago, Scott Adams said:

On page 26 of: https://gfco.org/wp-content/uploads/2024/05/GFCO-Manual.pdf 

So companies can perform the tests themselves, and not use any independent lab at all.

Oh my...

Also, Page 12 of https://gfco.org/wp-content/uploads/2024/05/GFCO-Manual.pdf: Companies wishing to apply for product certification need to complete the appropriate GFCO Certification Application and a non-disclosure/confidentiality agreement.

But why though? Food safety testing results shouldn't be confidential; it should be published publicly. The public interest is more important than any other interests when it comes to food safety.

[trents]

I believe Bob's Red Mill does their own testing. I called them some years ago and asked about what testing method they used and IIRC, this is what they told me.

[Scott Adams]

1 hour ago, GardeningForHealth said:

Oh my...

Also, Page 12 of https://gfco.org/wp-content/uploads/2024/05/GFCO-Manual.pdf: Companies wishing to apply for product certification need to complete the appropriate GFCO Certification Application and a non-disclosure/confidentiality agreement.

But why though? Food safety testing results shouldn't be confidential; it should be published publicly. The public interest is more important than any other interests when it comes to food safety.

I agree, but it's unclear what is contained in their non-disclosure agreement--if it includes not disclosing their test results it could be another red flag. It would be interesting to get a copy of the agreement to see what's in it. 

In a perfect world a certification organization would: 1) Require the use of an independent lab for all testing; 2) Not have a step down process where their testing requirements greatly dimmish over time if they continue to have negative results; and 3) Require the independent lab to provide results directly to the certification organization who would make them available online.

 

[trents]

Scott, I agree with your criteria and I don't think that is too much to ask. Those kinds of requirements are common practice in many other industries.

[GardeningForHealth]

In this thread, I initially assumed that I was experiencing "new" food sensitivities to non-gluten foods over time, and at an increasing rate. However, now I am re-assessing this assumption and asking myself, are these sensitivities actually due to ongoing exposures to gluten instead? 

I think we are uncovering important information here on this website about the state of gluten-free labeling and the organizations who are supposed to support consumers of gluten-free foods. What do we, as Celiacs and NCGS folks, need? We need clarity. We need to know if the foods we are eating contain gluten. Period!

And now we know that we cannot necessarily trust any company's marketing language or label; we need testing.

But that raises a new question; which testing(s) can we put our trust in? Are there tests which are more accurate than others? I would like to see more than one scientist who has years of experience in performing a variety of these tests discuss this topic publicly. However, even if that does not happen, the answer seems to be in doing more than one kind of ELISA test. For example, an R5 ELISA test and a G12 ELISA test.

Now, this raises yet another question that I am still trying to gain clarity on: The G12 ELISA test by Romer Labs when performed without a diluting protein. I want to talk about that now. 

This particular test claims in its brochure the following: 

Quote

 

Over the years, a few different antibodies became standard in gluten testing. Initially, the Skerritt antibody was most commonly used and tests based on it had Type 1 method status. It was replaced by the R5 antibody, an antibody developed in cooperation with the PWG. The R5 antibody was raised against rye secalin, but showed strong cross reactivity to wheat gliadin. It became quickly the “consensus antibody”, seen by many as the one, giving the correct answers. However, the change of the concept, detecting the immunotoxic peptides, playing a role in the pathogenesis of celiac disease, instead of detection of prolamins, led to the development of a next generation of antibodies. The G12 antibody belongs to this new generation.

The G12 antibody specifically recognizes the toxic fragment of the gliadin protein present in gluten. This fragment (called 33-mer) was identified by the University of Stanford and published in a paper 2002 in Science. Using the knowledge from this publication, the G12 antibody was raised against this 33-mer peptide. In contrast, the R5 antibody was raised against a secalin extract. The epitope it reacts with was later identificed as the QQPFP pentapeptide. The distinction between the two antibodies relates to the fact that the G12 antibody specifically targets the toxic fragment that triggers the auto-immune reaction in celiac patients, rather than a peptide sequence unrelated to clinical outcomes.

 

I would be curious how others are interpreting this statement, but to me this seems to imply the following:

• The R5 test is not as accurate as the G12 test, because R5 was created against rye secalin, and therefore its detection of wheat gliadins may be weaker than G12's detection of wheat gliadins.
• The G12 test is more accurate in its ability to detect proteins that are problematic for those with Celiac

The same brochure also states the following:

Quote

Detection of Oats
There is an ongoing debate concerning the presence or absence of gluten in oat. In fact, current antibodies were not recommended for the detection of gluten in oat. The G12 antibody has shed light on this debate due to its specificity for potentially immunotoxic sequences. G12 shows also a higher affinity to these sequences, which makes it much more sensitive, compared to other antibodies. It seems, that G12 can recognize oat varieties which trigger response in celiacs, while other oat varieties which are not causing any celiac response are not detected3. For this, the Spanish Celiac Association from Madrid has recently awarded the 6th National Price for Research on Celiac Disease to a scientific team that used the G12 antibody to select oat varieties that contain very low levels of gluten that are suited for their low pathogenicity for celiac patients.

Recently, I learned that about 10% of Celiacs react to oats (gluten-free, pure oats). More info on that here. In light of that information, it makes this G12 test even more remarkable, as this test picks that up.

Now I want to talk about "non-specific binding." Scott Adams states in this post:

Quote

Romer, the manufacturer of the AgraQuant G12 ELISA test, supported Dr. Fagan's claims, stating that while the milk additive is an option, it is not mandatory for all tests, and while certain ingredients like chocolate, soy, and oats, may require adding an extra protein during the testing procedure to prevent non-specific binding, they confirmed that no such ingredients were present in the Trader Joe's bagels.

My question is, why would we need to dilute the test by adding a protein? If this G12 test is finding immunotoxic sequences so accurately that it is able to verify the fact that some Celiacs react to oats, perhaps this test is correct in identifying potentially immunotoxic sequences in chocolate and soy as well; maybe we should not disregard this test binding to those proteins found in chocolate and soy; perhaps we need to take a second look at that and study that to see if Celiacs are also reacting to immunotoxic proteins found in chocolate and soy. Can these proteins trigger damage to the villi as well?

I finally had to stop eating chocolate, as it caused a reaction every time, no matter what brand of chocolate that I ate. I am willing to subject myself to testing to see if chocolate is causing villi damage. 

We need solid, verified answers that are backed by scientific tests. 

Is Celiac Disease expanding? It always seemed arbitrary to me that the definition of Celiac Disease stopped with wheat, barley and rye. Why just those three? Now we find out that 10% of Celiacs react to oats--and perhaps that number is underestimated? And I have now seen it being discussed on this forum that, cow's milk proteins are also causing a Celiac-like response.

Quote

Casein/Cow's Milk Intolerance
Research has shown that flattened villi can also be caused by casein intolerance. For more info see "Mucosal reactivity to cow's milk protein in C(o)eliac disease," which states "A mucosal inflammatory response similar to that elicited by gluten was produced by CM (Cows Milk) protein in about 50% of the patients with coeliac disease. Casein, in particular, seems to be involved in this reaction."