Non-Celiac Gluten Intolerance

[Rozzy1]

Hello everyone,

A customer of mine at the pharmacy has recently taken up a gluten-free diet without being diagnosed with celiac disease by their family Dr.
Instead, after reading on the net about "non-celiac gluten intolerance",  she purchased a testing kit from the following website:

https://www.enterolab.com/Home.htm

She read about the lab on a website by a gastroenterologist named Dr. Scot Lewey. His website/blog is below:

http://thefooddoc.blogspot.com/

She basically said that it's a new emerging problem that effects as high as 1 in 7 people and that this new method of testing ( as seen on Enterolab ) involves diagnostic tests on your stool sample, which indicates the presence of anti-gliadin antibodies better than your standard blood test.  They also test for casein and soy intolerance.

I tried searching Quackwatch, as well as the rest of the net to see anything about this new "disease" ( or any of these gastroenterologists on the website! ) but couldn't find anything.

Anyone heard about this?   I feel it would be unwise to just avoid gluten because some online lab tells you you're intolerant to it.   I guess she wouldn't be harmed if she did it properly, but it seems like alot of inconvenience.

[JJM]

Hello everyone,

A customer of mine at the pharmacy has recently taken up a gluten-free diet without being diagnosed with celiac disease by their family Dr. Instead, after reading on the net about "non-celiac gluten intolerance",  she purchased a testing kit from the following website:

https://www.enterolab.com/Home.htm {snip}

If her doctor is not involved, it is a good indication that this is bogus.  Look at the web site: "One particular area of our focus relates to intestinal conditions caused by immune reactivity to a protein called gluten which is found in wheat, barley, rye, and oats. Recent research in our laboratory indicates that immune [italics added] sensitivity to gluten" celiac disease is not an immune problem, it is a metabolic problem- inability to digest gluten.  Whether that gives rise to an immune reaction is irrelevant, the basic problem is metabolic.

"... immune sensitivity to gluten is exceedingly common, present in 30-40% of all Americans."  Can you believe the medical community overlooked something that happens to 1/3 of the population?!  

Where are the publications (any fool can submit a patent application)?  

This site has the hallmarks of quackery.

[bigtim]

Some people called Jews and Muslims avoid pork.  Others calling themselves Hindus avoid beef.  Still others will avoid caffeine and alcohol.

Someone elses food habits are not your business.

wow... is it me or is this over-aggressive?

I ask jews if they keep kosher all the time.  Some do, some don't.  I ask the muslims I know if they do too.  Everyone I've asked does.  I've asked hindis if they're vegetarians and some are, some aren't.   No one has ever been offended by that.  I ask folks if they drink too, had a mormon chuckle at me once when I offered her a beer, but still; no one was offended.

Pharmacists have patients and a duty to them just like doctors do.  So yeah, it is their business.

And I think your reaction to the OP is not warranted.

[bigtim]

doesn't sound like he's trying to force her to do anything; just sounds like a concern.  and, as a pharmacist it is his business if you're buying quack-tests

[Rozzy1]

Like bigtim said, I'm more concerned about my customers forking over $385.00 +  for unproven lab tests over a gluten-free diet...

There is nothing unhealthy about the diet... Hell i don't even eat that many breads, and opt for quinoa, brown rice, etc.

I'm more worried about the quackery that is at stake in this situation.

[JJM]

Enterolab offers tests for other "sensitivities" (such as yeast).  They are probably all bogus "diagnoses" the yeast certainly is:
http://www.quackwatch.org/01QuackeryRel ... ndida.html

[halsgluten]

As to the original question, my suggestion is to skip the "non-celiac" and just search on "gluten sensitivity".  An ongoing issue is how to classify people who do not fit the narrow definition of Celiac Disease, but nevertheless have clinical improvement on the gluten free diet.

I am posting on this old thread to counter what I see as perpetuation of an outmoded medical myth.  I realize the original participants may not be present to defend their arguement.  Please forgive the irregular post.

The following statement offered in critique of Enterolab's services is erroneous:

celiac disease is not an immune problem, it is a metabolic problem- inability to digest gluten.

The conventional diagnosis of Celiac Disease requires detection villious atrophy.  However, since villious atrophy is not specific to Celiac Disease, detection of specific antibodies is generally required in common practice to complete the diagnosis.  Inability to digest gluten may modify the condition, but it is not necessarily a prerequisite, and does not relate to conventional diagnosis, IIRC.  

At one time, the immune system involvement in Celiac Disease and other gluten sensitive diseases was not recognized.  One could only guess at what was happening.  Once the Lactose intolerance mechanism was broadly known; then it was guessed that Celiac Disease might be a similar "inability to digest gluten".  Yes, gluten is hard to digest, but that guess was naive.

As I understand it, the present state of the art is in understanding HLA (Human leukocyte antigen).  The HLA DQ2 serotype is highly efficient at presenting specific fragments (peptides) of gluten to the immune system as antigens.  The HLA DQ8 is somewhat less highly efficient.  Whether this presentation progresses to celiac disease or to other autoimmune disease (diabetes and others) is presently hypothesized as being dependent on the presence of other genes, especially within in the HLA.

To dispel the notion that some atypical “inability to digest gluten” gives rise to the immune response, consider this.  One's digestion cannot produce the prerequisite peptides unless one can digest gluten, at least to the level of the peptides in question.  But even if one can completely digest gluten past the peptide level, there are nevertheless ample peptide digestion intermediates present.  So, at least to some point, the more completely one can digest gluten, the greater the amount of hard-to-digest gluten peptide intermediates one presents to the immune system, posibily. However, I immagine individual digestive systems may present different concentrations of intermediates to the immune system.

So, Celiac Disease does not rise from individual inability to digest gluten.  Also, I think it is a bit casual to use the term “metabolic problem” to classify the inability to digest anything as somehow distinct from some other disorder.   A metabolic process is any chemical process in the body that maintains life.  Digestion problems are just one type of many possible metabolic problems, and I think not all possible digestion problems are rooted in a metabolic problem.

Where are the publications (any fool can submit a patent application)?  

Dr. Fine has over 20 publications on Pubmed under “Fine KD”.  These papers generally lay the foundation for his stool testing, but to the consternation of some customers, he has not published since his patent, around 2001.  

As I understand it, his stool tests conventionally assess the state of the digestive tract health and theoretically assess immune system progression towards autoimmune disorders including Celiac Disease at a stage earlier and more treatable than possible with more conventional blood tests.  To be generous to Dr. Fine, for him to prove the theory and publish, the study must run 10-20 years, I’d guess.

Is it uncommon for researchers to stop publication once they turn their research into a business, legitimate or not?

[hydrogen hypothesis]

Thanks for the post above halsgluten, good points.

I get a red flag when I see a researcher or scientist making claims about a process or product that they turn around and start offering for sale. Whether his claims are legitimate or not, there needs to be a lot more research in this area.

An ongoing issue is how to classify people who do not fit the narrow definition of Celiac Disease, but nevertheless have clinical improvement on the gluten free diet.

I work in the natural food industry. I see many people who are absolutely sure they have gluten sensitivities, or some kind of allergy that I find unlikely. (For example a customer my develop contact dermatitis from skin contact to vitamin e and then assume this means they should avoid vitamin e even in the small amounts found naturally in foods, or the tiny amounts that are added to oils to preserve them. This is unnecessary.)

Awareness of gluten intolerance/sensitivity is on the rise, but with this we should be careful not to diagnose people who are simply suffering from so-called "normal" digestive issues due to bad diet as having gluten intolerance or celiac disease. Celebrities and others love to hype these things up into a frenzy because it makes them richer. And people love believing that if they just follow this new diet or take this new product, they will by healed.

Gluten may be difficult to digest, but I notice that when people are concerned about allergies or gluten they are forced to become aware of everything they eat, and the magic bullet "answer" that most people will pay hundreds for, is unavailable to them. By avoiding gluten they are forced to look at options they wouldn't normally. And since they may just be starting to become more aware and concerned about their health, they may be feeling better simply because they are eating better.

[fromthehills]

I like it when folks say they are allergic to wheat, and have switched to spelt. They get angry with me when I tell them spelt is wheat.

[hydrogen hypothesis]

Yeah, it also contains gluten. Although it may have not have the allergen that common wheat has. In fact the wiki link mentions that, although when I started doing any digging around for scientific studies I found none.

On the other hand, some people actually get tested for their allergies rather than just relying on their "symptoms" and confirmation bias to lead them 'round. I wouldn't assume offhand that just because they suffer less symptoms its always everytime a placebo reaction. Maybe I'm mistaken, but common wheat (and grains that are used as staples for along time) does have a predisposition to become an allergy in at least a percentage of the population of which it is a staple. Some japanese have rice allergies as it is the staple grain of japan. http://www.gulfmd.com/Immunology%20-%20 ... .asp?id=18

[halsgluten]

Thank you for the welcome

I get a red flag when I see a researcher or scientist making claims about a process or product that they turn around and start offering for sale.

yeah, it’s a common way to push a hoax, but it is also a way to get a good product on the market 10-20 years faster than through the doctor's office.

some kind of allergy that I find unlikely

IgE allergies are rare, but intolerances and IgG and IgA hypersensitivities are common.

tiny amounts that are added to oils to preserve them

Tangent: I reckon that if the oil is in a form that needs a preservative, that raises a flag to me that the oil is in a bad form.

they may be feeling better simply because they are eating better.

 Some Enterolab charts show that everybody gets better on the GFD, whether they are positive or negative on the Enterolab test.   Since it is also evident that the Enterolab test has a high false negative rate (about half that of the serum test), I think the number of false negative Enterolab customers who try the diet and feel better anyway should be relatively high.

[halsgluten]

I wouldn't assume offhand that just because they suffer less symptoms its always everytime a placebo reaction.

There are genetic bases for a wide range of severities.  Even if one is "DQ2.5", you may be espressing at 100%, 75%, 50%, or 25% due to effects of heterogeneity of isoform pairing.  Then there are several milder DQ2 haplotypes with the same heterogeneity effects.  A variable  period of mild or severe sensitivity precedes development of any classic Celiac Disease.  Then there are DQ2 and other haplotypes that lead to gluten sensitive conditions other than Celiac disease. So yes, there is a such thing as "Non-Celiac Gluten Intolerance/Sensitivity".

Maybe I'm mistaken, but common wheat (and grains that are used as staples for along time) does have a predisposition to become an allergy in at least a percentage of the population of which it is a staple. Some japanese have rice allergies as it is the staple grain of japan.

 I've wondered at that, too.  I wonder if there is a cultural survival benefit to food sensitivity -- a higher rate of mild autism should increase technical innovation, mad dogs and Englishmen and all that....a Neurotypical would know better than to pack gunpowder and rocks into a length of pipe...

[hydrogen hypothesis]

IgE allergies are rare, but intolerances and IgG and IgA hypersensitivities are common.

That makes sense, I can't really drink milk in large quantity, but yogurt and cheese seem fine since the culture consumes most of the lactose. From this website: http://digestive.niddk.nih.gov/ddiseases/pubs/lactoseintolerance/

Yogurt made with active and live bacterial cultures is a good source of calcium for many people with lactose intolerance. When this type of yogurt enters the intestine, the bacterial cultures convert lactose to lactic acid, so the yogurt may be well-tolerated due to a lower lactose content than yogurt without live cultures. Frozen yogurt does not contain bacterial cultures, so it may not be well-tolerated.

Some customers I've asked have it as I do, but others seem to be so unable to consume it that they suffer diarrhea and extreme nausea. Casein or milk allergy is commonly confused with lactose intolerance. Is casein allergy really an IgE allergy or an intolerance/hypersensitivity?

Tangent: I reckon that if the oil is in a form that needs a preservative, that raises a flag to me that the oil is in a bad form.

Specifically fish oils have small amounts of added vitamin e. Usually the oil is molecularly distilled. I have "heard" that this makes the oil rancid, but this information is also industry based. That is, a company who does the opposite and doesn't molecularly distill their fish oil has nasty things to say about the companies that do. Besides industry b.s., though I had noticed a better less nasty burp-back taste from the product, but that could just be confirmation bias....

Some Enterolab charts show that everybody gets better on the GFD, whether they are positive or negative on the Enterolab test.   Since it is also evident that the Enterolab test has a high false negative rate (about half that of the serum test), I think the number of false negative Enterolab customers who try the diet and feel better anyway should be relatively high.

I dislike the deception, whether it be self-deception or otherwise, involved in misdiagnosis, but at least the silver lining is that the diet is beneficial rather than harmful. The problem for me in this industry is the how it is all lumped together, both in the minds of skeptics and alternative health practitioners alike: being conscious of dietary health and sound nutritional advice is right there next to homeopathy in our resources bookshelf. Unfortunately the wheat and chaff haven't been separated yet.

[hydrogen hypothesis]

I've wondered at that, too.  I wonder if there is a cultural survival benefit to food sensitivity -- a higher rate of mild autism should increase technical innovation, mad dogs and Englishmen and all that....a Neurotypical would know better than to pack gunpowder and rocks into a length of pipe...

Yeah, though I doubt we lack shortage in imagination, our species has so many creativity stimulants (No, not coffee, though that is one of them.) that we may actually have an excess in processes that produce innovation. We're better at building new things than we are in adapting to them. I think any sensitivity wasn't so much a benefit to group selection so much as it was not a hindrance to survival of our procreating ancestors. This also is a big reason why the human body starts to wear so early even with diet and exercise, production of certain antioxidants are greatly reduced by as young as age 25. There isn't an evolutionary reason why we should maintain perfect health and vigor beyond this age. Allergies and food sensitivities do occur in young people, but seem to become more debilitating and common as we age.

[halsgluten]

Some customers I've asked have it as I do, but others seem to be so unable to consume it that they suffer diarrhea and extreme nausea.

 Naturally, there are varying degrees of intolerance, since multiple factors are involved varying between individuals, for instance, the loss of lactase effectiveness may be 10%, may be 90%.  Yogurt products have a range of lactose content.  Some cheese have verly little lactose, some have a lot.

Here’s where you get me to open up my skepticism, but it’s off topic to this thread.  I question the “yogurt” status of “refrigerated yogurts”. I think these "candies" are made with as little fermtation of the lactose as possible (they are also enriched with lactose from milk solids).

Casein or milk allergy is commonly confused with lactose intolerance. Is casein allergy really an IgE allergy or an intolerance/hypersensitivity?

A casein intolerance case might be a hypersensitivity, might be an IgE allergy, or might be neither.  The layperson may call any intolerance an allergy (it is often a lot easier that way).  A classic allergist will only call the IgE response an allergy and at most call and IgG or IgA response a “delayed allergy”, but more likely a hypersensitivity, sensitivity, or intolerance.

Intolerance includes both digestive enzyme failure and immune sensitivity -- sensitivity includes IgG, IgA, and IgE response, but classically, the word "allergy" is used for IgE only.
IgA = border police
IgG = highway patrol
IgE = regular infantry
Gluten-Triggered Autoimmunity = when you have very large amounts of illegal border crossers that are practically indistinguishable from citizens.
Celiac Disease = the highway patrol starts shooting at the border police

Specifically fish oils have small amounts of added vitamin e.

Whereas, if the fish oil was still in the whole fresh fish, you wouldn’t need to add the vitamin e.  Added antioxidant is needed only to prevent unsaturated fat oxidation after the fish’s antioxidant systems fail post mortem.

Usually the oil is molecularly distilled. I have "heard" that this makes the oil rancid

 Oxidation is what makes an oil rancid.  Removing the oil from living tissue (animal or grain) promotes oxidation.  Enteric coating also reduces burping.

I dislike the deception

I don’t see overt deception in Enterolab.  (the best improvments were with positive test results plus gluten feee diet -- the least imprvements were with no diet)  I see a doctor that connected the dots between his liver disease patients and celiac patients.   I think he sees the risks of not trying the diet (likelihood of disease times the severity of the disease) as bigger than the risks of trying the diet (likelihood of no disease times the severity of the diet).  Aren't his organizations non-profit?

[halsgluten]

Allergies and food sensitivities do occur in young people, but seem to become more debilitating and common as we age.

Autism is a condition that occurs in the young,  while there are likely to be multiple causes, it strongly coincides with food sensitivities.  

The way I see it, great discoverys have come from people with "circumscribed interests", isolation from social "distractions", and are too foolish to realise that they are "wasting their time" on a stupid theory.

[JJM]

...  The way I see it, great discoverys have come from people with "circumscribed interests", isolation from social "distractions", and are too foolish to realise that they are "wasting their time" on a stupid theory.

I have been away for a while; but let me say that your posts are missing definitive citations.  It is not enough to say that somebody's papers can be found in PubMed, you must tell us which particular publications support which particular claims.  An allergy that is prevalent (30-40% of the population) that is only known to one person is a red flag for quackery.  It seems to have been removed from the web; but the site linked in the OP was full of it (quackery).  If you think otherwise, be specific.  Celiac disease, as we know it, is not an immune disorder.

[halsgluten]

[Is celiac disease is an immune problem?]

Thank you, JJM, for coming back to this old thread.

I interpreted the OP question ("Anyone heard about this?") as questioning to there is such a thing as "non-celiac gluten intolerance".   As I saw it, you (JJM) first questioned Dr.  Fine's credibility on the fact that Dr. Fine associated gluten sensitivity with Celiac Disease with your statement "celiac disease is not an immune problem".

To get to the question of Dr. Fine's status, I see a need to get past other questions.

This is your earlier statement that drew my attention to this thread:

celiac disease is not an immune problem,

Celiac disease, as we know it, is not an immune disorder.

By "we" did you mean the Skeptic forum?
By "immune disorder", do you exclude autoimmune disorder?  The University of Maryland Center for Celiac Research and the University of Chicago Celiac Disease Center both introduce the subject with the statement "Celiac disease is an inherited autoimmune disorder".
http://www.medschool.umaryland.edu/celiac/treatment.asp
http://www.celiacdisease.net/assets/pdf/CDCFactSheetsOverview1.pdf

Celiac is described as an autoimmune disease, autoimmune disorder, or autoimmune enteropathy in a number of current publications:  
http://www.ncbi.nlm.nih.gov/pubmed/21119542
http://www.ncbi.nlm.nih.gov/pubmed/21091908

The NIH lists celiac disease as an autoimmune disorder:
http://www.nlm.nih.gov/medlineplus/ency/article/000816.htm

And I read:
"Celiac disease is now considered to be an immune disorder ...."
http://www.ncbi.nlm.nih.gov/pubmed/21180248

[celiac disease is] inability to digest gluten

The article "Recent advances in coeliac disease" (Gut 2006;55:1037-1046) states "These changes in clinical practice have been paralleled by a dramatic increase in our knowledge of disease pathogenesis, making coeliac disease the best understood human “autoimmune” disorder".  
http://gut.bmj.com/content/55/7/1037.full
The section "Clinical Implications of Basic Science Advances", discusses steps in coeliac disease pathogenesis.  "These steps include: (i) a (putative) direct response of the epithelium via the innate immune system to toxic proteins in wheat gluten, (ii) modification of wheat gluten proteins by tissue transglutaminase, (iii) role of HLA-DQ2 in presenting toxic wheat proteins to T cells, and (iv) identification of key toxic protein sequences in wheat (fig 3). These advances have introduced the possibility of novel therapeutics (distinct from the gluten free diet) to treat coeliac disease."  
I do not see in that article, or in any other current article I've read, where Celiac Disease rises from any pathological inability to digest gluten (analogous to lactose intolerance).  "The immunogenic gliadin epitopes, containing multiple glutamine and proline residues, are largely resistant to degradation by gastric and intestinal proteases."*  The antigens are hard to digest even without some digestive enzyme problem.

* http://www.ncbi.nlm.nih.gov/pubmed/20948997

I believe that is it correct to say that celiac disease is an immune problem that causes digestion problems.

Thus, I don’t think simply refering to “immune sensitivity to gluten” is a basis for criticism of a doctor.

[halsgluten]

The peer reviewed literature on stool test for antigliadin antibodies seems to be few in size, small in participants, and mixed in results:
(Edit: I have no expectation that each of these studies used the same processes or assessment criteria)

http://www.clinchem.org/cgi/reprint/39/4/696
Increased Concentrations of Fecal Anti-Gliadln IgA Antibodies in Untreated Celiac Disease (Clinical Chemstry, 1993)

http://www.ncbi.nlm.nih.gov/pubmed/15481630
“The most promising results in our study with higher concentrations in patients with celiac disease were obtained by fecal scIgA AGA and a combined determination of fecal IgA AGA, IgG AGA and IgM AGA.”

http://www.ncbi.nlm.nih.gov/pubmed/16377644
“Neither stool test was suitable for screening for coeliac disease in children with symptoms.”

http://www.ncbi.nlm.nih.gov/pubmed/11808976
" IgA AGA levels were higher in untreated CD patients than in treated CD and control patients,"

[halsgluten]

[How can that be!?]

"... immune sensitivity to gluten is exceedingly common, present in 30-40% of all Americans."  Can you believe the medical community overlooked something that happens to 1/3 of the population?!
AND
An allergy that is prevalent (30-40% of the population) that is only known to one person is a red flag for quackery.  

First, Celiac Disease is not an allergy in the sense that IgE is classically required for that definition.  But yeah, I used to believe that to claim that 1% of the population was gluten sensitive was quackery.  However, with Fasano’s publication in 2003 and some others reporting that the prevalence of biopsy-proven Celiac Disease alone was around 1 percent, with the discovery of gluten sensitivity causing Dermatitis herpetiformis and forms of ataxia when biopsy-proven Celiac Disease is not present, and with the knowledge that the Celiac Disease diagnosis algorithm excludes people with gluten antibodies but no biopsy presentation, and given that gluten sensitivity should precede progression to biopsy visibility, then the prevalence of gluten sensitivity must be greater than 1%.  For other reasons, my guess came to be around 10% for the prevalence of AGA antibodies.

Citations for the 1% prevalence of biopsy-proven Celiac Disease :

“Prevalence of Celiac Disease in At-Risk and Not-At-Risk Groups in the United States: A Large Multicenter Study”, Alessio Fasano, et al., Archives of Internal Medicine, Vol. 163 No. 3, February 10, 2003.
“High prevalence of silent coeliac disease in preschool children screened with IgA/IgG anti-endomysium antibodies.” Korponay-Szabò IR, Kovács J, Czinner A, Gorácz Gy, Vámos A, Zsabò T., Journal of Pediatric Gastroenterology and Nutrition, 1999; 28: 26-30.
“One Percent of Italian Schoolchildren have Celiac Disease”,  Archives of Disease in Childhood, 2004;89:499-501,512-515.  Review on Celiac.com
“Celiac Disease Present in 1% of 5-Year-Olds in Study”, Reviewed by: Steven Dowshen, MD, http://www.kidshealth.org/
“Adult coeliac disease: prevalence and clinical significance.” Cook HB, Burt MJ, Collett JA, Whitehead MR, Frampton CM, Chapman BA., Journal of Gastroenterology & Hepatology, 2000 Sep;15(9):1032-6.
“Coeliac disease, an emerging problem in developing countries”, Carlo Catassi--Istituto di Clinica Pediatrica, Università di Ancona, 2002.

But, "HLA-DQ2 or HLA-DQ8, or both, are found in approximately 40 percent of the general population, but in more than 99 percent of patients with celiac disease."  ("Celiac Disease", Am Fam Physician. 2007 )
http://www.aafp.org/afp/2007/1215/p1795.html
HLA-DQ2 and HLA-DQ8 both efficiently present gliadin fragments to T-cells, which signals production of anti-gliadin antibodies.  (I do not know whether it is impossible for other HLAs to present gliadin fragments to T-cells, especially in high doses.)
http://en.wikipedia.org/wiki/HLA-DQ
http://en.wikipedia.org/wiki/HLA-DQ2
http://en.wikipedia.org/wiki/HLA-DQ8
So, if a new and reasonable method of assessing AGA shows prevalence in the range of 30-40%, I would personally no longer reject it out of hand.  But, yes, Dr. Fine’s prevalence of 30-40% has not been reviewed.

Can you believe the medical community overlooked something that happens to 1/3 of the population?!

Can you believe the medical community overlooked something that happens to 1% of the population?!  The University of Chicago Celiac Disease Center says, “WHY IS IT DIFFICULT TO FIND A DOCTOR THAT KNOWS ABOUT CELIAC DISEASE? Most physicians learned during medical school that celiac disease was so rare they would never see a patient with symptoms in their entire medical career.” [Doctors I’ve asked use essentially the same words.]
“Lectures on celiac disease in medical schools, even today, are few and far between. When your doctor was in medical school, he or she may have heard a 20-30 minute celiac disease lecture during four years of classes. Medical textbooks still contain outdated information.  Additionally, celiac disease often presents with seemingly unrelated symptoms, such as fatigue, joint pain, anemia and infertility, making diagnosis that much more difficult.”
http://www.celiacdisease.net/assets/pdf ... rview1.pdf
Now, if that level of outmoded understanding applies to the most researched presentation of gluten sensitivity, what level of understanding applies to the more prevalent, less researched presentations?  

A big question is just how clinically significant are serum or stool antigliadin antibodies (AGA)?  Because AGA has correlated poorly with villous atrophy, it has come to be conventionally regarded clinically insignificant. [rhetorically] “OK, so what if there is high prevalence of AGA?  If AGA prevalence is that high, it oviously can’t mean anything.”

But, if there is AGA in the body, and there is gluten in the diet, then there is immune response, that’s just what antibodies and antigens do.  But, how important is that response, in most cases it must be mild, or if would be noticed, and if it is mild, it might not mean much for many.  Maybe for most people, they have health habits much worse than mild gluten sensitivity.

[halsgluten]

[Where is the paper?]

It is not enough to say that somebody's papers can be found in PubMed

I think I generalized -- I have usually read criticisms that Dr. Fine has NEVER published ANYTHING, where as he has a long track of peer reviewed publications leading up to 2001.  Indeed, you only asked,  "Where are the publications...?", so, you were asking specifically about the reviewed publications of the  30-40% prevalence of stool IgA for gliadin in the general population?  True, that has not been repeated or peer reviewed.  

A search of the Forums of Celiac.com for “Enterolab” will find many discussions of validity and questions about publication.   In particular, there was the thread on the “Group Letter to Dr. Fine”

On 29 January 2009 - 12:52 PM, a report of response from Enterolab to the Group letter was posted.
Around 2006, Dr . Fine was saying he was going to announce his results (I personally recall this much), but then according to the post, “Dr. Fine and his staff also made the difficult decision to go back and do tedious additional research concerning long term results from dietary compliance. All of these decisions take time and yes, definitely took MUCH time away from Dr. Fine's paper getting finished, right at the very time when he was pushing himself and promising many of us to get it done. I [the reporting forum member] got the impression that they are very determined that this research be absolutely accurate and well prepared no matter how long it takes.”

This report by the "Advanced Community Member" said Dr. Fine was on a 3-6 month sabbatical to finish the paper.

In response to the group letter, Dr. Fine modified Enterolab’s “FAQ Gluten/Food Sensitivity” at Enterolab.com.  The 2009 link does not  work now but pieces were captured on the "Gluten Free and Beyond Forums":  
"However, symptomatic people with gluten sensitivity but without the celiac reaction in the small intestine often require a more prolonged period of gluten removal before experiencing any or complete remission of symptoms, and more often require attention to other dietary antigenic offenders like other grains (including rice, corn, and oats), milk products, foods with added yeast, and soy, among others."

A copy of a statement in a promotion of Dr. Fine's gluten-free family camp was posted  07 February 2009 - 04:05 PM:
"Research Publication Update from Dr. Fine ... I am in the final stages of writing a scientific publication describing to the medical and scientific communities how effective stool testing for diagnosing gluten sensitivity has been over the past 10 years that we have been doing it."

Then on Jun 18 2009, someone claiming to “do work for” Enterlab claimed knowledge that the paper had been submitted.  

I have no other knowledge of a pending paper from Dr. Fine.

[halsgluten]

I have wanted to more thoroughly address the original question,  but ran out of vacation.

Non-Celiac Gluten Intolerance …I tried searching Quackwatch, as well as the rest of the net to see anything about this new "disease" ( or any of these gastroenterologists on the website! ) but couldn't find anything.   …  Anyone heard about this?

To answer this question, we must parse it because there are two points that must be clarified.  First, to identify a “non-celiac condition”, we must decide on the definition of “Celiac”, which is not necessarily straightforward.  Then we must decide what the original poster's customer meant by the term “intolerance”, again a possibly loosely defined term.  Because the OP was looking for information on the “new disease”, I presume that the OP wanted to know if there is such a thing as “Non-Celiac Gluten Intolerance”.

Neither of the sites referenced in the OP use the term “Non-Celiac Gluten Intolerance”, but rather they use the term “Non-Celiac Gluten Sensitivity”.  The Scott Lewey site seems to qualify “intolerance” and “sensitivity”, and “allergy” as having distinct meanings.  Enterolab generally uses the term “gluten sensitivity” rather than “gluten intolerance”.  In the few places where Enterolab uses the term intolerant or intolerance, it is in clear reference to the state of being “immunologically intolerant to gluten”, which would be consistent with general use of “sensitivity”.

Personally, I used the term intolerance to include all forms of sensitivity, but there are recommendations that limit “food intolerance” to sensitivities that are “non-allergic” ( but include IgA and IgG reactions with allergic sensitivities). [1][2]  But, the Merck Manual Online Medical Library uses the terms “gluten sensitivity” and “gluten intolerance” interchangeably for Celiac Disease.[3]  And, if you search the forums on http://www.celiac.com, you might find that that Celiac community uses the terms “gluten sensitive” and “gluten intolerant” interchangeably.  So, will read the OP as being concerned with “Non-Celiac Gluten Sensitivity”.  

But what is “Celiac” so that I may know what is “non-Celiac”?

Most simply put, Celiac Disease is injury to the upper small intestine caused by immune reaction to gluten.  Regardless of blood or stool tests, complete conventional diagnosis requires positive small intestine biopsy before diet therapy and negative biopsy after treatment with the gluten free diet, or at least positive symptoms on subsequent gluten challenges.[3]  At least “Four possible presentations of celiac disease are recognized:
(i) typical, characterized mostly by gastrointestinal signs and symptoms;
(ii) atypical or extraintestinal, where gastrointestinal signs/symptoms are minimal or absent and a number of other manifestations are present;
(iii) silent, where the small intestinal mucosa is damaged and celiac disease autoimmunity can be detected by serology, but there are no symptoms; and, finally,
(iv) latent, where individuals possess genetic compatibility with celiac disease and may also show positive autoimmune serology, that have a normal mucosa morphology and may or may not be symptomatic.
The diagnosis of celiac disease still rests on the demonstration of changes in the histology of the small intestinal mucosa”[4]
Confounding this definition is “Refractory Celiac Disease” which could be Celiac Disease so advanced that the gluten free diet has no effect; thus you can’t complete the diagnosis by gluten challenge.  

Furthermore, common practice might not confirm cases fitting  (ii) atypical or (iv) latent celiac disease as really being Celiac Disease.[3][5]  In simpler words, it might be said by a doctor in such cases that if you do not have positive biopsy, you do not have celiac disease.

It rather depends on how broadly you define Celiac Disease.   If you define Celiac Disease narrowly, requiring obvious villous atrophy, then there will be more cases of gluten sensitivity that are non-celiac, but if you define celiac disease so broadly as to include all forms of gluten sensitivity and if you define gluten sensitivity as getting better on the gluten fee diet, then there will be no cases of gluten sensitivity that are non-celiac.

I think Enterolab clinically defines “gluten sensitivity” as the presence of antibodies to gluten,  I think that is technically correct (if tautological on my part?).  Enterolab also seems concerned with preventing development of celiac disease.  The real question up in the air is whether or not the gluten free diet should be applied simply because you are clinically sensitive to gluten via IgA or IgG mechanisms.   I would hope that would be the question answered if someone would publish.

Research is progressing in “non-celiac” conditions suspected of gluten sensitivity:

Dermatitis herpetiformis is a clear case of a generally non-celiac condition that responds to a gluten free diet. “A strict gluten-free diet will also be recommended to help control the disease. Sticking to this diet may remove the need for medications and prevent later complications.”[6]

The highest risk Celiac alleles are present in high rates in type 1 diabetes patients:
“[The study indicates a] possibility that in some individuals, type 1 diabetes may be induced by wheat proteins. Also, it provides a first candidate wheat protein that is not only antigenic in diabetic rats and human patients but is also closely linked with the autoimmune attack in the pancreas.”[7]

Gluten free diet is under study as treatment for forms of ataxia and ganglionopathy :
“Gluten ataxia is an immune-mediated disease triggered by the ingestion of gluten in genetically susceptible individuals. It should be considered in the differential diagnosis of all patients with idiopathic sporadic ataxia. Early diagnosis and treatment with a gluten free diet can improve ataxia and prevent its progression.” [8]
“Although neurological manifestations in patients with established coeliac disease have been reported since 1966, it was not until 30 years later that, in some individuals, gluten sensitivity was shown to manifest solely with neurological dysfunction. Furthermore, the concept of extraintestinal presentations without enteropathy has only recently become accepted.” [9]
"Sensory ganglionopathy can be a manifestation of gluten sensitivity and may respond to a strict gluten-free diet." [10]

So, I conclude that there exist conditions that are both non-(typical)-celiac and gluten sensitive, and that there exist people without celiac diagnosis who could be healthier on a gluten free diet, but at this time it is difficult to clinically identity such people when they are not clearly celiac.


[1] [A revised nomenclature for allergy] Johansson SG, Hourihane JO, Bousquet J, et al, Allergy (September 2001)  56 (9): 813–24.
[2] [Revised terminology for allergies and related conditions].[Article in Dutch] Gerth van Wijk R, van Cauwenberge PB, Johansson SG., Ned Tijdschr Tandheelkd. 2003 Aug;110(8):328-3
[3] [Celiac Sprue] Merck Manual Online Medical Library
[4] [Celiac disease: risk assessment, diagnosis, and monitoring.] Setty M, Hormaza L, Guandalini S., Mol Diagn Ther. 2008;12(5):289-98.
[5] [Celiac Disease - Exams and Tests] Webmd.com
[6] [Dermatitis herpetiformis] MedlinePlus, http://www.nlm.nih.gov
[7] [A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked to islet damage.] MacFarlane AJ, Burghardt KM, Kelly J, Simell T, Simell O, Altosaar I, Scott FW., J Biol Chem. 2003 Jan 3;278(1):54-63. Epub 2002 Oct 29.
[8][Gluten ataxia] Hadjivassiliou M, Sanders DS, Woodroofe N, Williamson C, Grünewald RA., Cerebellum. 2008;7(3):494-8.
[9][Gluten sensitivity: from gut to brain] Marios Hadjivassiliou MD, David S Sanders MD, Richard A Grünewald DPhil, Nicola Woodroofe PhD, Sabrina Boscolo PhD, Daniel Aeschlimann PhD, The Lancet Neurology, Volume 9, Issue 3, Pages 318 - 330, March 2010
[10][Sensory ganglionopathy due to gluten sensitivity] Hadjivassiliou M, Rao DG, Wharton SB, Sanders DS, Grünewald RA, Davies-Jones AG., Neurology. 2010 Sep 14;75(11):1003-8.

[halsgluten]

This just in:

American Journal Gastroenterol. 2011 Jan 11.
“Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease:
A Double-Blind Randomized Placebo-Controlled Trial.”
Biesiekierski JR, Newnham ED, Irving PM, Barrett JS, Haines M, Doecke JD, Shepherd SJ, Muir JG, Gibson PR.

“Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism.”

This study took 34 patients with irritable bowel syndrome but without clinical celiac disease who had improvement of their IBS by means of the gluten free diet. (that is, some form of "Non-celiac gluten intolerance"). Some were fed gluten and some a placebo for six weeks.
Those eating gluten got significantly worse within 1 week.
As they got worse, nothing appeared in their labs suggestive of celiac disease.

Even more interesting, even though the patients demonstrated that gluten affected their pain, bloating, stool, and fatigue, they never demonstrated antibody sensitivity to gluten by blood test.  So, they could not event be said to have "non-IgE mediated food allergy",

Gluten may or may not have had a role in the development some or all of these patients' IBS, and it may be that that the root cause of some or all of the studied IBS cases also caused primary or secondary gluten intollerance, but they were intollerant, according to the abstract.

CONCLUSIONS: "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated".