So can we say that gluten cross-reacts with your thyroid and just leave it at that? Well, not really, and not with it maybe as much certainty as we want, but without a doubt, through multiple converging mechanisms, gluten exposure and Hashimoto's are linked together. The bottom line is that for everyone who eats gluten, there's a transient leaky gut, a transient surge of inflammation, a negative impact on your microbiome, a change in blood flow to your brain, and more. Welcome back.
This is the Inflammation Nation podcast, where we'd like to stay up to date on current science and how that can help you craft your wellness journey. Today is part two of is gluten really that bad for you? And before we continue on, I want to give you a short recap of part one of this two-part series. In part one, I covered the fact that gluten is just One of several protein or protein complexes within wheat that you can react to.
Wheat proteins are divided between gluten proteins like gliadin and glutenin. And non-gluten proteins are things like serpens, pharinins, as well as amylase trypsin inhibitors or ATIs for short. With gliadin, there are three subtypes, which are named alpha, gamma, and omega. The one that has received the lion's share of attention is the alpha gliadin version, which is what was identified back in the 1940s as being the trigger for celiac disease.
And it wasn't until the early 2000s that my immunology mentor, Dr. Aristo Vojdani created the first lab test that checked the entire spectrum of gluten proteins that we moved from one-dimensional testing for celiac disease to looking at the broader reality of what gluten really is. So for about 60 years or so, the only test that was available to us was focused entirely on identifying celiac disease, which led to the idea in conventional medicine that as long as you didn't have celiac disease, you were okay to eat gluten. But as I mentioned last time, that if you're reacting to, say, the gamma-gliadin version of gluten or the omega version, or even some of the other proteins, then you would test negative for celiac disease and you would be encouraged to continue to eat gluten.
And I say encouraged intentionally, because there is this ridiculous concept in the nutritional sciences. And you see this mostly in mainstream conventionally trained dietitians and nutritionists. There's this idea that wheat is an essential part of the human diet. And you'll hear over and over that wheat contains essential vitamins and minerals and fibers.
And if you cut wheat and gluten out of your diet, you're going to compromise your nutrition in several different ways. And to that I say "Poppycock!". There is no nutrient in wheat that you can't find elsewhere. And whatever calories you reduce by not eating wheat and gluten, you can easily be replaced by better options.
And I have to point this out because it's not unusual for self proclaimed experts to say that when people go gluten-free and say they lose weight, it's because they simply reduce calories, not because they removed an inflammatory food that triggers a transient state of leaky gut. Most people who go gluten-free replace the lost calories by switching to products that are labeled gluten-free. So calories on average stay about the same. Another point that I made in part one is what I just mentioned a second ago.
There are two mechanisms by which eating gluten and wheat can trigger a transient leaky gut. In part one, I shared how the gliadin portion of gluten increases the production of zonulin, which causes the gut barrier to open up. And the same thing can be said of the non-gluten protein called amylase trypsin inhibitor. This binds to toll-like receptor 4 and does several things we don't want.
First, it also opens up the gut lining, causing a transient leaky gut, but it also triggers new inflammation from the innate immune system, which is made up of cells like neutrophils and macrophages and natural killer cells. Plus, it amplifies any pre-existing inflammation that's already there. What's worse? Is that a paper from 2020 in the Journal of Gastroenterology showed that these ATIs in wheat and other grains remodel the microbiome to the extent that they inhibit anti-inflammatory species of good bacteria and they promote the proliferation of bad bacteria.
And the literature literally says that in this respect, ATIs found in the highest concentration in wheat and other gluten-containing grains have the same effect on your microbiome. As prescription antibiotics. The net effect of consuming grains with ATIs exert a selective antibiotic effect that fuels pro-inflammatory immune responses, especially once the barrier is already compromised. And let me add one more insult to the injury.
You've heard me and others talking about lipopolysaccharides or LPS for short. LPS are toxins that are produced by certain bad bacteria in your gut that can cause inflammation and leaky gut. But it turns out that some of these types of bacteria live in wheat and other grains. And some research says that at least part of the effect of ATIs on inflammation, leaky gut, and the microbiome, is due to LPS contamination, where it binds to the amylase trypsin protein, which we then consume.
And here's the kicker. ATIs and lipopolysaccharides exist in all grains of all kinds. I'll toss this up on the screen for you. It turns out that what little research that has been done on this shows that LPS is found in higher concentrations in the gluten-containing grains like wheat, rye, and barley, but it's also highest in whole grain versions because the bacteria and the LPS toxins live in the outer shell of the grain.
So for decades we've been told to eat whole wheat and use whole grain cereals. Could it be that this very recommendation has been making us sicker and more inflamed because whole grains are contaminated with LPS toxins and this gets thrown into the mix of what these amylase trypsin inhibitors do to drive inflammation, create transient leaky gut, and dysregulate your microbiome just like antibiotics. And if you're looking at this list, I have up on the screen, you'll see that rice has very low levels of ATI, but that's white rice, not brown rice. Remember back in the 80s, there was this massive switch to brown rice and whole grains because it had more fiber and it was supposedly healthier for you.
But brown rice has the highest amount of these ATI proteins than any other grain, including wheat. And it also contains very high amounts of LPS toxins. And remember, all grains contain ATIs and LPS. Not to mention the lectin content.
That's a whole different conversation. So is it any wonder that so many people who go grain-free and adopt a paleostyle diet do so well? That's a massive pro-inflammatory load that's taken away with just one choice. All right, so I've done the summary and I've digressed enough.
But I think that was really a bunny trail that was worth exploring. So let's move on to core concept number two. And let me explain the actual difference between celiac disease and non-celiac wheat sensitivity. Where is the line?
How do we draw the distinction? Well, like I said earlier, the thing that most people and conventional doctors get wrong is that they treat a gluten problem as a binary system or like an on-off switch. You either have celiac disease or you're fine with gluten. And that's not how it works.
It's a spectrum. And celiac disease is only the most extreme, most clearly defined point on that spectrum. Celiac disease actually is an autoimmunity, and non-celiac wheat or gluten sensitivity is not. For all of us, when we eat gluten-containing foods, the cells that line our intestines produce an enzyme called transglutaminase to help digest it.
But in someone genetically primed with the HLADQ2 or DQ8 gene variants, gluten exposure also triggers your immune system to build transglutaminase antibodies, specifically transglutaminase two. And since you already know that when your system, when your immune system makes an antibody to something, it directs other parts of your immune system to attack it wherever it is. And since the transglutaminase two Enzyme lives in and around your intestinal cells. As your immune system attacks that enzyme, it also damages the intestinal cells themselves.
And over time, immune-mediated destruction flattens these little finger-like projections that come off the lining of the gut that are called villi. They're used to trap and absorb nutrients for your gut. And you get a very real, very measurable disease. We have confirming blood work, there are confirming biopsy findings.
And there's a genetic risk profile. So, in reality, celiac disease is not up for debate. It's a real thing. We know how to find it and we know how to define it.
It's one of the best characterized autoimmune conditions in medicine. And again, it's an autoimmune response to an enzyme called tissue transglutaminase 2, which is found in your intestines. Non celiac gluten sensitivity is a different animal. And here's where the last year of research actually started to shake things up.
A November 2025 review out of the University of Melbourne, published in the journal The Lancet, pulled together and controlled trial data on non-celiac gluten sensitivity and found that a meaningful chunk of people who believe they're gluten-sensitive react to gluten, wheat, and placebo about the same. And the researchers proposed that at least Some of what gets labeled as gluten sensitivity is actually driven by other wheat components, fermentable carbohydrates called FODMAPs, for instance, that we might see a problem with IBS or SIBO, or even by a gut-brain feedback loop where the expectation of a reaction shapes the actual experience of one. And they estimate somewhere around 10% of the global population identifies with having gluten sensitivity. Which is a much bigger group than the roughly 1% who actually have celiac disease.
But I want to be careful here because it would be easy to hear that and think, so it's all in my head. I'm just imagining that I have gluten sensitivity. And that's really not what the research says, and it's not what I'm telling you. Real physiological gluten reactivity outside of celiac disease absolutely exists.
We're about to walk through several mechanisms for exactly that. What this tells us is that the label gluten sensitivity has been getting used as a catch-all for several different things that need to be teased apart, a real direct immune reaction to gluten, a reaction to other wheat components like serpents, pharinins, ATIs, and LPS, a gut that's irritated by FODMAPs, and you would expect to react to things like onions and garlic just as much as bread, and a genuine gut brain sensitivity pattern. Where anxiety about the food is part of the physiology, not separate from it. Lump all of those things into one bucket labeled gluten sensitivity, and you'll never actually fix the right thing.
So here's how we reframe this. It's not, do you have celiac disease or not? That's too simplistic. It's where do you land on a spectrum from confirmed autoimmune disease like celiac with a biopsy to prove it, Or having an allergy or sensitivity to gluten, having reactions to non-gluten proteins all the way down to reactions to highly fermentable FODMAP foods like we see in IBS and SIBO, and even including the psychological aspect of the gut brain connection.
That's the real question. And knowing where you actually sit on that spectrum is the whole point of the testing section that we'll see coming up later in this episode. So let's get into The specifics that I promised you before I said at the end of episode one that we were going to talk more about gluten's connection to leaky gut. We're going to connect gluten and changes in blood flow to your brain.
And we'll talk about something that's bandied about in clinics and on the internet a lot, which is gluten cross-reacts with your thyroid. Three different mechanisms, three different levels of evidence. And I'm going to go be straight with you about which is which. So, what does the last 12 months of research actually show?
Well, we've already covered the mechanisms as to how gluten can cause a transient leaky gut. But what's new in the last 12 months of research isn't that mechanism, it's measurement. A study published in the journal Frontiers and Immunology in September of last year took healthy volunteers with no celiac disease, had them fast, gave them a measured 10 gram dose of gluten. That's about three slices of bread or maybe a cup of pasta.
Then they tracked a marker called urinary gluten immunogenic peptides, or UGIP for short. They looked at that in their urine for the next 15 hours. And they found that gluten fragments showed up in the urine within about three hours and peaked around four to five hours later. What that means is if you're eating gluten several times a day, you're constantly triggering this transient leaky gut that peaks at five hours, but it lasts longer than that. then every single day you're walking around with not a transient leaky gut, but a connected series of transient leaky guts, which is a constant self-inflicted one because it never really resolves in between the doses of your gluten-containing lifestyle.
Now, this test isn't available commercially. This is only in the research world. And while we do have leaky gut tests like Cyrex Labs Array number two, which is my favorite, we have to be careful not to confuse the issue here. There is a physiological difference between a transient leaky gut caused by gliadin or amylase trypsin inhibitors.
There's a difference between them and the leaky gut caused by damage to the gut lining. Tests like Cyrix Array 2 detects leaky gut from damage to tight junction proteins that keep the gut barrier intact. And this type of leaky gut is somewhat of an enduring state. It's not a transient one like that caused by gliadin or zonulin or ATIs.
And you might hear that and say, well, my doctor tested my zonulin levels and said that I don't have a leaky gut. Well, just hold on a second. Blood tests For zonulin vary from hour to hour throughout the day. So the timing of that test, especially relative to the last time that you consume gluten, makes a huge difference.
The literature is pretty clear that the blood zonulin test is not a reliable test. It's not something that I would run on myself. So diagnostic companies then started testing zonulin in stool, which is more consistent throughout the day, and that's better, but it's still only an indirect measure of leaky gut. And I want to point you back to the two universals that link transient leaky gut to both gliadin and ATIs, and the fact that this happens in everyone, regardless of whether or not they react to gluten from an immune standpoint.
And it happens anytime you eat gluten. For the next five plus hours, you have a transient leaky gut not rooted in damage to tight junction proteins, which means regular leaky gut tests won't find it. And all of this begs the question. If everyone who eats gluten gets a transient leaky gut, why can some people eat gluten and not get symptoms from it?
And yes, those people do exist, believe it or not. Well, the difference is in the balance and control of the rest of their physiology. People who are not inflamed, not infected, they have good blood sugar control, they're not stressed, their adrenals are fine, they have a balanced microbiome making lots of short-chain fatty acids. They've got good hormone balance and good thyroid control and so on.
They can get away with eating gluten and having a transient leaky gut because it's not going to cause anything after that. And it's not that for these people, they don't get the transient leaky gut. They do. They just have good immune competence control and balanced physiology such that despite getting that transient leaky gut, their systems are stable and resilient enough to handle it.
Okay, let's move on. To the next deliverable, and that's about how eating gluten can change blood flow to your brain. And this is a real issue. But it's also older than most of the internet content that's repeating it these days.
So let's get the actual data right. Back in 2004, so 22 years ago, researchers in Rome used a brain imaging technique called SPECT to scan blood flow in the brains of 45 people, 15 with untreated celiac disease. And 15 with celiacs who've been gluten-free for about a year, and then 15 healthy controls. And it's difficult to do these tests because you have to have access to the imaging machine.
It costs a lot of money to do that. This is why sometimes the numbers of people involved in the studies aren't in the hundreds or in the thousands. But here's the result: 73% of the untreated celiac disease had at least one region of reduced blood flow to their brain. Most often the frontal cortex, and that's the part of your brain responsible for planning and focus and concentration and executive function.
In contrast, only 7% of the celiacs already on a gluten-free diet saw changes in blood flow to their brains. That's a big difference. It's a real striking reproducible finding. And that's part of why brain fog shows up so often as a celiac disease symptom, not just a gut symptom.
And what's new this year is the framing, not new brain scans. An April 2026 review in the journal Brain and Heart pulls this older imaging data into a modern context called the gut-brain heart axis. And they propose that an intestinal barrier disruption, the leaky gut that we talked about before, drives systemic inflammation, which in turn stresses your blood-brain barrier and injures the small blood vessels that feed your brain. And it's a plausible unifying mechanism.
And the authors are upfront that there are still real gaps in exactly how that works. but here's the honesty check, and it matters. That hypoperfusion data is specific to confirmed celiac disease. It's not hard evidence that everyone with non-celiac sensitivity has reduced blood flow to their frontal cortex, but that doesn't mean we're out of the woods yet. Whether it's the inflammation caused by an immune response to gluten or non-gluten proteins, or the amylase trypsin inhibitors activating the innate immune system and amplifying preexisting inflammation, or if it's the effect of LPS contamination, or even the escape of LPS from the gut because you're always triggering a transient leaky gut, all of these factors can impair the function of the blood-brain barrier, cause neuroinflammation, which then causes.
Neurovascular uncoupling. Now, I've talked about this in a couple of prior episodes, but the term neurovascular uncoupling, that's a fancy way of saying that the communication between your brain and its own blood supply is altered, such that when the neurons that you use to think and move and feel with activate, the blood vessels fail to dilate to deliver the blood and nutrients that your brain needs to work harder. This is how the system is designed. Blood flow gets shunted to working areas of your brain on demand, so that neurons that you're not using much get less blood flow.
And when they activate, they get more. Of course, like any other system, it's much more complex than I can present here. But one of the key drivers of this uncoupling of brain activity and blood flow is brain inflammation. And there's a ton of research linking gluten to changes in the blood-brain barrier as well as triggering.
Neuroinflammation. There's also a connection here that's mediated by an immune reaction to tissue transglutaminase 6. Remember in the last episode and earlier, I explained that when people have celiac disease, they eat gluten, their immune system makes antibodies to transglutaminase 2, which lives in intestinal cells. Well, there are other types of tissue transglutaminase, and transglutaminase 6 is found in the brain and nervous system tissue.
When someone who makes antibodies to tissue transglutaminase 6 and they eat gluten, the direct result is an autoimmune reaction inside the brain itself. But whether the mechanism is gluten impairing the blood brain barrier, Or a transglutaminase six autoimmune reaction, or simply the neuroinflammation that's a consequence of gut inflammation, the results are almost always the same. You eat gluten and you get brain fog, lack of mental clarity, slower mental processing, and a brain that tires out with the simplest of tasks. So while the original research on how gluten affects brain blood flow has been done in people with celiac, that does not mean that non-celiacs who react to wheat and gluten in any number of ways are exempt from the effect on blood flow to the brain.
And the more scientists study and unravel this, the more ways they find that gluten impairs your brain. And that brings me to my final deliverable: gluten and cross-reactivity with your thyroid, especially in the context of Hashimoto's hypothyroidism. This is the one I get asked about constantly by patients already managing Hashimoto's, and it's the one where I want you to hear the nuance instead of the highlight. A review published in Frontiers and Endrochrinology in May of this year laid out four candidate mechanisms connecting gluten to autoimmune thyroid disease, gut dysbiosis or infection, and barrier dysfunction bridging inflammation from your gut to your thyroid.
Immune cross-reactivity, meaning your immune system might mistake a piece of gluten for a piece of thyroid tissue because the two look similar at a molecular level. That's your actual cross-reactivity, molecular mimicry idea. Shared epigenetic patterns between celiac and thyroid autoimmunity, as well as a general immune spillover from a leaky gut. And the authors conclude that the idea of gluten being involved in Hashimoto's.
Is likely not a simplistic model of gluten cross-reacts with your thyroid. In other words, quote, these processes may converge with molecular mimicry and defective immune regulation to facilitate thyroid autoimmunity. So can we say that gluten cross-reacts with your thyroid and just leave it at that? Well, not really, and not with it maybe as much certainty as we want, but without a doubt, through multiple converging mechanisms, gluten exposure and Hashimoto's are linked together.
The bottom line is that for everyone who eats gluten, there's a transient leaky gut, a transient surge of inflammation, a negative impact on your microbiome, a change in blood flow to your brain, and more. And once gluten or non-gluten reactivity like LPS and ATI fires off the inflammation, that alone can trigger your Hashimoto's independent of whether gluten cross-reacts with your thyroid. And whether or not future research definitively proves that gluten proteins cross-react with the thyroid remains to be seen. But don't let the lack of clear science on that one point convince you that it's okay to eat gluten when you have so many other reasons not to.
All right, core concept number four. Let's talk about testing. This is where more most people get it backwards. A lot of people go gluten-free first, and they may or may not feel better.
And then sometime in the future, they want to get tested to see if they're gluten sensitive while they're still gluten-free. Well, here's the problem with that. If you cut gluten before you're tested and you make every single antibody test in that section come back with a false negative because your immune system stops making antibodies that it only makes when gluten is actually in your system. And it takes about six weeks for those to clear out.
So the rule is that if you want to do a gluten sensitivity test, you have to be eating gluten. And if you have been gluten-free for six weeks or more, and doing a good job of that, because sometimes it's easy to get accidentally exposed. Some people think being mostly gluten-free counts, but it doesn't. So if you're gluten-free for more than six weeks or so and you're doing a good job, don't waste your money on a test because you're not going to get good reliable data.
In my opinion, the top two lab tests for full spectrum gluten testing, including non-gluten proteins, are Cyrex Lab's Wheat Burden Test and a test from Vibrant Labs, which is simply called wheat. And you can't really order these by yourself. So if you're interested in having one of these tests done, you can reach out to me with. The contact information in the episode, and we can set up a consultation to go over your goals and we can make a plan for you.
Far fewer people have celiac disease compared to the much larger number of people who have gluten allergy or sensitivity. For every 10 people with gluten sensitivity, there's only one person with celiac disease. So unless you have a family member with celiac disease, I would start with either the Cyrex or the vibrant gluten panels. Think of the standard celiac panel like a smoke detector that is only in one room of your house.
It'll catch a fire in that one specific room every single time, but it doesn't tell you anything about all the other rooms in the house. And Cyrex and Vibrance wheat panels are more like the whole house detection system, right? More sensors, more rooms covered, catching things that a single detector was never built to see. That doesn't mean that you install the whole house system for every single person walking through the door.
It means when the room one room detector comes back clear and you're still clearly smelling smoke, somewhere in the house, you don't just shrug and assume that you just imagined it. You bring in better instruments. So what I mean by that is if your doctor tested you for celiac disease and it was negative and they say you're fine to eat gluten, do not accept that. You have to have further testing and Cyrex Labs environment.
Those are the two panels that I would trust. So where does that leave us? As the title of the episode prompts, is gluten really that bad for you? Well, it depends.
If you're one of the lucky ones who don't react and can even tolerate your transient leaky gut that affects everyone, then no. At least not yet. The moment your health slips and your blood sugar destabilizes or your gut gets wonky or your hormones are out of whack and you're inflamed, then yeah, all of a sudden. That thing, gluten, that you've been able to tolerate for years, all of a sudden is part of the problem.
But if you eat gluten and you're experiencing any of the symptoms that we talked about throughout this episode, whether that's brain fog and lack of mental clarity and fatigue and on and on and on, then for you, gluten is poison and you need to stop. Let me say the core point one more time, because it's really the whole episode. You cannot sort out where you land on the spectrum. by how you feel after just a simple elimination diet, you have to actually test for it in the right order with the right panel for your specific clinical picture. That's an exact kind of untangling that I do with people in my practice every week, patients who've been gluten-free for three years and still don't know actually if they're gluten sensitive or have celiac disease, or maybe it's patients with Hashimoto's who are told to cut gluten without any clear explanation as to why.
Or even hypothyroid clients who've never had their thyroid antibodies checked. They don't know if they have Hashimoto's, and they still are playing around with gluten in the diet because they're not committed one direction or the other. Now my practice is virtual. I'm based out of Florida, but I work with people across the country and internationally, mostly women.
That's changing over the years, but I help people navigate exactly this kind of tangled multi-system picture. Often after a few other doctors have already told them. That they don't know what's going on, or maybe they have, and they said, Well, your labs are normal. Everything should be fine, but it's clearly not.
So if gluten is a question mark that's hanging over your own health, there's a contact form on my website, drnoseworthy.com, where we can talk about what testing would actually answer that question for you. Thanks for listening to The Inflammation Nation. Remember to put your big rocks in first, stay rooted and grounded in the fundamentals, and I'll see you on the next episode.
