I've a good eye for bullshit, which is why I didn't take Wheat Belly or Grain Brain particularly seriously until the diet surprisingly worked for me. But the more I looked into it, the more silly some of their foundational claims seem. So I've looked into it for myself, and it seems the following two-step process explains pretty much everything that all of the gluten-free experts seem to be getting wrong:
1. Something or some process damages the gut flora / intestinal permeability, allowing partially cleaved gliadin to enter the bloodstream at a rate greater than the body can handle. Once damaged, the continued presence of gliadin sustains that damage to the intestines. This is why 'gluten sensitivity' or autoimmune response to gliadin can occur at any age.
2, Partially cleaved gliadin acts as a catalyst in the amylin/insulin/protein process to misfold proteins into amyloid fibers.
That's it. If these two statements are true, all problems known and claimed to be related to gluten (including celiacs, but also every nutjob like me) suddenly have a foundational biological disruption mechanism that explains pretty much everything else.
If you don't have a medical degree in organic biochemistry and can't make the instant connection from these claims to the "game over" conclusion, I will elaborate. But first, let me provide supporting arguments for the first two claims.
1. Intestinal Permeability / Gut Dysbiosis / Zonulin (prehaptoglobin-2).
If you're not familiar with the research into Intestinal Permeability or Zonulin, please go research it. If you are familiar with it, this latest study is of interest:
What the actual spark is between the normal intestinal response to gliadin, and full blown intestinal permeability is not fully known, but gut dysbiosis, infection and gliadin itself are suspected. Given that serum zonulin studies are linking intestinal permeability to a much wider range of illnesses than just celiacs, it's a very important unanswered question.
The study above, however, indicates that partially cleaved gliadin fragments may be entering the bloodstream of anyone eating gluten, just not at high levels without full blown permeability. This reaction explaining studies like this:
This leads me to believe that the gliadin reaction is just a matter of degree and quantity, regulated by the permeability of the intestines. More permeability: more problems.
2. Gliadin Catalyzes Amyloid Formation
This is the connection that I haven't seen anyone, world renowned Doctor, Scheister, or lone whack-job (except me), claim or explain, but I ran across a group of studies researching amyloid formation that were using hydrolized gliadin to induce the misfolding process.
The Role of Protein Hydrophobicity in Conformation Change and Self-Assembly into Large Amyloid Fibers 2014
Kinetics of Peptide Aggregation 2011 (full thesis paper from student involved in above study).
Basically, in the presence of insulin, amylin & proteins, gliadin fragments catalyze the formation of amyloid fibrils. Now, these are all ex-vivo studies, but chemistry being what it is, there's no reason the same thing doesn't happen in-vivo.
So when gliadin enters the blood stream, the body is left to cope with two problems it creates: amyloid fibrils that are difficult to dispose of, and a disruption of the proper functioning of all the different amylin processes when gliadin reacts first.
Without digging in too deep right now amylin disruption would affect appetite, insulin levels, lipid production, along with secondary effects of excess free transglutaminase (along with any other amine/acil bonding catalysts I'm unaware of), and lack of appropriate structure for new tissue, because there's insufficient amylin after reacting with gliadin.
Amyloids are known to aggregate in any region of the body, and the illnesses associated are generally defined by the area they choose to.
The more amyloids that are produced (greater intestinal permeability + more gliadin in the diet), the greater the problems, and that's when the immune systems may kick into high gear. What's generally termed an 'autoimmune' response, is in this situation an adaptive immune response, attempting to target the problem, but with major collateral damage. In some, that target is directly to the gliadin fragments, in others, it's to the leftover products of the disrupted amyloid process (like transglutaminase), and yet others, it might even be to the other half of the gliadin-produced amyloid. There's no law of nature dictating the adaptive immune response must be to the gliadin.
For that matter, there's no biological law dictating there must be an autoimmune response at all. In some people, probably most people, it would be all innate immune response, and thus currently not diagnosable. Without an autoimmune response, the typical result would likely be: excessive hunger, overeating, hypo/hyperglycemia from the amylin/insulin disruption. Then as amyloids accrue and overwhelm the body's natural ability to remove them: insulin resistance, followed by T2 diabetes, and the progressive amyloidosis organ failures associated there-after that generally kill. Or if you're really unlucky, Parkinson's or Alzheimer's.
So, if 1 & 2 are correct, gliadin really does affect everybody - the key factor likely being simply how much gliadin gets into the blood. If it's greater than the body's ability to remove the amyloids, they will become a problem. If you're unlucky, you'll have an autoimmune response, but if you're lucky, it'll be celiacs, so you'll at least know how to treat it. If you're luckier, you won't have problems until you turn 40 or 50 when the amyloids that have collected start causing diagnosable problems, and you can take metformin or have bypass surgery or thyroid pills or whatever. If you're really lucky, you have a strong gut and autophagy response and you get to be one of those 115 year old bastards who attribute their age to bacon, Dr. Pepper, and cigars.
There's more - there's always more; but if you've read this far, I challenge you to debunk my theory. I also invite you to apply my theory to any claim people like Dr. Perlmutter or Dr. William Davis make on behalf of gluten-free, in place of their own explanations. I invite you to look closely using this theory at the debunking of Dr. Perlmutter and Dr. William Davis by such noted science journalists like Hank Campbell at Science 2.0. I invite you to look again at Dr. Gibson's double-blind cross-over studies as last-word on GF for the ignorant. I invite you to submit research links, proclaim this or that, just give me something to work with. I'm a big kid. The silence is deafening.
Until then, though, it's now called "Gliadin-Induced Amyloidosis". No more of this NCGS nonsense. And I'll stop blogging about it, too, since I'm now bored with the topic having convinced myself I've figured it out.