I have a piece on “gluten myths” in the NYT Sun Review. It’s received a fair amount of attention. And I’ve received a few unhappy emails.
So a few clarifications:
The piece in no way argues that people who have problems with gluten shouldn’t go on a gluten free diet. In fact, it acknowledges the robust evidence of a real increase over time in celiac disease.
And although this isn’t in the piece, I suspect the non-celiac gluten sensitivity that scientists still argue about (is it real? How do we measure it?) will turn out to be real as well. I wouldn’t be surprised if a spectrum of gluten-related disorders exist that, as a group, ends up afflicting a sizable ppercentage (maybe 6 percent?) of the population.
Those afflicted will clearly benefit from avoiding gluten. The piece in no way contradicts this idea. Nor does it dispute that some people have unusual symptoms from eating gluten, including neurological and / or psychiatric problems that then DISAPPEAR on a gluten free diet, something I’ve written about in these same NYT pages.
I believe it. What I find wanting, however, is the explanation for our problems with gluten — that we haven’t evolved eating it long enough, and so on.
I could pick at many a nit, but one way to cut through the clutter — because there’s so much — is to understand the underlying immunology of celiac.
THE FUNDAMENTAL NON-DIGESTIBILITY OF GLUTEN
Some propose that we don’t digest gluten well, and that large fragments leak across the gut barrier, enter circulation and then are viciously attacked by our immune system. It’s true we don’t completely break down all gluten. But there’s lots of stuff we don’t completely digest. Non-digestibility doesn’t automatically mean attack.
In reporting, I asked one scientist what he thought happened to the undigested gluten fragments in non-celiac people. He very sensibly said they were probably broken down (digested) by colonic microbes further down in the intestinal tract. And whatever entered circulation was either excreted in urine, like other wastes, or metabolized somewhere in the body.
In what organ? No one really knew, he noted, because no one has done precise studies on it. But here’s the point. Just because you don’t completely digest a protein does NOT mean that you mount an immune response against it.
Which brings me part B of this argument: Won’t gluten leaking into circulation prompt an immune response? In order for your immune system to attack a protein, some kind of “danger” or “stress” signal must also accompany it. There needs to be a reason for the attack — a sign of something amiss.
As an exercise in understanding these dynamics, consider how allergy shots work. You’re injecting proteins that you normally attack — pollens, say — directly into your body. The amount is gradually increased. And after many jabs and many months, you eventually stop sneezing during hay fever season. Your body learns tolerance.
Consider that this process of building tolerance depends on your body NOT attacking proteins in circulation. It only works because your immune system does not automatically attack injected substances, EVEN IF you have an allergy to it.
Now consider how vaccines work. You’re after a different outcome: you want the immune system to attack the protein and remember it as threatening. For this reason, vaccines often include adjuvants — substances that intrinsically stimulate the immune system. Without these adjuvants, your body might ignore the protein—might tolerate it. The vaccine might not take.
So: A protein leaking into circulation — let’s just say gluten fragments — by no means guarantees that you’ll mount an immune response against the protein. You need some kind of adjuvant — a signal of damage or stress or attack.
Yes people argue that gluten (gliadin and glutenin) are inherently immunostimulatory. More on this in a moment.
But first, Bana Jabri, one of the sources in the articles, has some nice new papers on some of OTHER pre-existing factors that are necessary for celiac to emerge. She calls the process that leads to disease a “perfect storm.” Clearly you need gluten. But her research suggests that you also need ALREADY STRESSED intestinal cells to develop overt celiac. By what? Microbiota anyone? Viral infection?
WHAT ABOUT THOSE HLA TYPES?
Two HLA types (DQ8 and DQ2) account for nearly ALL celiac cases. HLAs (also called MHCs) are like molecular grasping claws on the outside of our immune cells. They grasp and hold bits of protein. And then, with those protein fragments in those molecular grasping claws, these cells “educate” other cells in the immune system. They say, “here’s what the invader looks like. Now go get ’em!”
The thinking on these HLA types in celiac is that they’re really good at holding bits of gluten. The protein just happens to fit right in — like a burr sticks to velcro. And that, according to this argument, is the problem. Carriers of these HLAs are just accidentally very good at “grabbing” gluten fragments. So they’re more prone to initiating the attack that leads to celiac disease.
What this telling completely overlooks — which is very important — is that just because a molecule fits into those grasping claws well does not mean that other cells are more likely “learn” to attack that molecule. That’s because these so-called antigen-presenting cells — the cells holding the fragments — can in fact instruct other cells NOT to attack the protein they present. They can go either way: thumbs up or thumbs down.
Again, this is how allergy immunotherapy works. By exposing yourself to minute but growing amounts of allergen, you’re really getting these antigen presenting cells to say, “See this? Don’t attack it. Leave it alone. ” That’s how you build tolerance.
In the context of celiac, one could argue — and Jabri made this point when we spoke — that because gluten fragments fit particularly well into those grasping claws, carriers of the associated gene variants should be really good at developing tolerance to gluten.
The point being that a talent for binding of MHC molecules to gluten fragments does not equal an immune response to gluten. It could just as likely enhance tolerance-building to gluten.
Again, the mystery is what convinces those antigen-presenting cells to present gluten as dangerous. That’s the real mystery of celiac disease.
BUT DOESN’T GLUTEN INCREASE GUT PERMEABILITY?
I’ll come back to this in a future post. But for now, suffice it to say that increased permeability does not automatically mean disease. There are a number of contexts, in fact, where you could imagine — hypothetically speaking — that increased permeability might be a good thing. Stay tuned.