Is There Evidence for Gluten Causing Brain Disease?

[nomadreid]

There is a New Zealand pediatrician named Dr. Rodney Ford whose bête noir is gluten. Gluten sensitivity (I'm not sure whether "Coeliac disease" is a synonym or simply associated with it) and gluten intolerance are of course serious concerns, but I wonder whether he doesn't sometimes goes overboard, as in the (popular) article
https://www.celiac.com/articles.htm...ase-by-prof-rodney-ford-mb-bs-md-fracp-r1071/
in which the headline proclaims "Gluten Causes Brain Disease!" In the article, he is a bit more cautious, pointing out that his claims are mainly guesswork, citing "circumstantial evidence" (the closest I found between, for example, gluten and MS was in the articles
https://jamanetwork.com/journals/jamaneurology/fullarticle/2279878
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905342/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065402/ )
Is there any solid foundation for Dr. Ford's proposed links between neurological damage and coeliac disease?

 

[jim mcnamara]

Okay. Physicians have to be given a kind of leeway. They are more applied scientists, with a touch of some extra talents.

A story: I taught at a college associated with a hospital. I was talking to the senior MD. He looked at some people walking into the waiting room. He went over to the triage nurse and asked her to get the sick boy who just came in, into an exam room right away. A while later I bumped into him. And he said, 'I was right, I thought I saw bulbar polio.' So he had 'seen' something. Physicians do this. He had practiced in Tanzania for years and apparently encountered a lot of polio. Another Doc used to come into the waiting room, and 'count respirations (her term)' and get the people in trouble into the exam room faster. Triage nurse did some of this too.

This is what a lot of what physicians do. It is what we need to have them do. And then there is the physician who 'saw' something with people who used aspartame, or ate gluten, or used MSG. We do not want to tell them they are not being scientific. But someone reading this material from out of the blue and who does not know this, cannot tell what is going on. So they are inclined to accept the ideas.

Clinical practice and pure biology research are very definitely different things.

Coeliac disease is basically gluten intolerance. Coeliac disease: https://celiac.org/celiac-disease/understanding-celiac-disease-2/what-is-celiac-disease/ The rate is about 1 in 100 people. Other patients show different levels of response from complete dibilation (celiac) to more generalized or diffuse symptoms - non-coeliac gluten sensitivity.

This is different from what Rodney Ford wants to present. It seems he wants to completely vilify gluten, which may not be the best possible position.

Non-coeliac sensitivity to gluten in a small percent of the population: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017515/

Note how NIH spells celiac as does celiac.org I went with your ceoliac. Hope you're happy with that.

 

[nomadreid]

Thanks, Jim. However, I am not sure that Ford can "see" a connection between nerve damage and celiac disease (I'll go with that shorter spelling; Wiki uses both). The concrete case I am concerned with is a person with MS, and a relative of the affected person who is thinking about paying for the patient to take a blood test for celiac disease as the relative suspects, after reading Ford, that celiac disease is at the basis of the MS (logic from a superficial reading of the statistics: MS--nerve disease with small percentage of population; celiac disease ---according to Ford---, nerve disease, also rare. They "must" be connected.) I would like to give the relative some information on any possible connection or lack thereof from someone who is a bit less hysterical than Ford.

 

[jim mcnamara]

There is a physician in the US who promoted the idea that Azheimers is Type III diabetes, Dr Mark Hyman.
Literature review on the subject: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/ - a strong maybe.

Since there isn't much new on this hypothesis it probably has been put on a back burner.

This current article indicates a concurrency of AD and impaired glucose metabolism is an invariant condition - an association, not necessarily direct causation.
https://www.sciencedirect.com/science/article/pii/S0960982216308533

I'm no expert on MS but NIH has a lot of articles on a clinical perspective of MS and celiac + non-celiac gluten ataxia. It seems to be in the same category as AD and glucose metabolism.

From an evolutionary point of view - we evolved to find and eat. We evolved to tolerate deprivation and starving. The better we were at getting food the more likely we + our offspring would live to reproduce.

Overconsumption of food and eating synthesized food were never something that we evolved to deal with. It happened very rarely up until the 20^th century. So it will never surprise me if and when we find a solid connection between diet and diseases...

Diabetes type II is a perfect example of something that would never have been selected against on any scale. Primary cause is overconsumption of calories, usually as carbohydrate. It is now rampant.

 

[nomadreid]

Thanks again, Jim. The two links were interesting in showing possible correlations between nerve conditions and glucose pathways. Analogous research for MS could be fruitful -- not as a continuation of these articles, because gluten is a protein and glucose is a sugar, so they follow two different pathways after their initial separation in digestion. But analogous.
Whereas many of the incidents of diabetes can be linked to over-consumption, it seems that gluten sensitivity arises independently of the quantity of food. As for the quality of the food, we evolved to eat grains very early on, so it would would not be the introduction of gluten that would trigger it. Thus it would seem that gluten sensitivity is either a left-over from humanity's pre-grain history, or more likely simply a glitch -- whether by factors connected to diet or not is unclear. In any case, the question is not where the gluten sensitivity comes from, but rather, given that there is a gluten sensitivity in a person before any signs of MS arise, could the gluten sensitivity have any part in causing the MS? Since the causes of MS are still not clear, this question can have only tentative answers, and the links I provided in my original post indicate that there may be a weak statistical correlation, but no direct causal link, no mechanism, was outlined in those papers. However, I may have overlooked some research in my googling, or missed out on some reasoning somewhere. Obviously I am not looking for a definitive answer, just indications as to whether there are any reasonable mechanisms, some causal chain, that have been proposed with some sort of credibility.

 

[nomadreid]

This is different from what Rodney Ford wants to present. It seems he wants to completely vilify gluten, which may not be the best possible position.

Non-coeliac sensitivity to gluten in a small percent of the population: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017515/

I also thought that Dr. Ford, as well as another popular vilifier of gluten, Dr. David Perlmutter, were being rather extreme. However, this morning someone sent me the following:
http://www.drperlmutter.com/wp-content/uploads/2016/07/nutrients-07-01565.pdf
with
"Conclusions:
Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity."
On one side, as you can see from the address, the study was accessed via one of Perlmutter's websites, but on the other hand Perlmutter himself was not involved in the study. Then, on one side the journal is an MDPI journal, which is, according to Wikipedia, a group which included predatory journals in 2014, but on the other hand the group is now no longer listed as such. The study looks credible to my untrained eye, but I would appreciate an assessment of the (short) study and its conclusions from someone more qualified than I am.

 

[jim mcnamara]

@nomadreid
I assume below, when I mention leaky gut which is an edgy concept, that you got a link from Perlmutter that led you to the paper.

Celiac disease does manifest itself as changes to the gut tissue lining - human epithelium. What the paper reported experimenting on.

They are probably seeing the effect of IL-10 (an anti-inflammory cytokine, "turns off" inflammation).

What the paper says in every day terms, is that people with symptoms and an already active gliadin(gluten) response, when exposed to more, get worse faster. It is related to the IL-10 level. Gliadin is a form of gluten found in wheat flour - see: https://en.wikipedia.org/wiki/Gliadin

I don't get what is going on - relating this to anything we talked about. In other words, I'm confused. I guess this establishes that the duodenal epithelium is degraded in people with a gluten response. Okay. How does this cause all the other things we talked about?

I am suspecting anyone citing this paper is thinking about leaky gut. Not a great choice.

FWIW: Gut tissues can become "leaky" letting some molecules out into the bloodstream - ones that normally do not get out. This is from a few known disease processes that alter the gut tissues. AFAIK celiac disease is not one of them.

This opinion piece indicates that we should not overreact and assume leaky gut everywhere.
https://www.ncbi.nlm.nih.gov/pubmed/26760399
Another different and more dire opinion:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

The take away is that these are largely opinion pieces.

 

[nomadreid]

Thanks very much, Jim.
All very interesting, even though, as you point out, it is difficult to see any link that leaky gut has to celiac disease, and even if there is a link, how this leads to a link between celiac disease and other autoimmune diseases such as MS. Apparently some people are nonetheless attempting to make the connection, albeit without any solid success as of yet, as mentioned not only in the paper you cited,

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440529/

"In individuals with a genetic predisposition, a leaky gut may allow environmental factors to enter the body and trigger the initiation and development of autoimmune disease." (my emphasis) but also in less rigorous articles such as:
https://www.health.harvard.edu/blog/leaky-gut-what-is-it-and-what-does-it-mean-for-you-2017092212451:
"We already know that increased intestinal permeability plays a role in certain gastrointestinal conditions such as celiac disease, Crohn’s disease, and irritable bowel syndrome. The biggest question is whether or not a leaky gut may cause problems elsewhere in the body. Some studies show that leaky gut may be associated with other autoimmune diseases (lupus, type 1 diabetes, multiple sclerosis), chronic fatigue syndrome, fibromyalgia, arthritis, allergies, asthma, acne, obesity, and even mental illness. However, we do not yet have clinical studies in humans showing such a cause and effect." (my emphasis)
As you said, it seems like guesswork at this point.

 

[BillTre]

Here is a Science mag news article of gluten sensitivity and related problems.
It came out last month.

 

[nomadreid]

Thanks, BillTre. Very interesting article, and the video is well done. Given the confusion about Gluten, it is no wonder that the possible connections to other diseases is even more remote.