Dr. Michael Ruscio: Hey, everyone. This is Dr. Ruscio. Let’s discuss some important updates regarding gluten sensitivity or more technically known as non-celiac gluten sensitivity. Essentially, if you’re trying to get healthy, you’ve likely heard something about gluten-free and there’s varying opinions on this at both ends. Some will have you believe that you should vehemently avoid gluten. Some would have you believe that gluten-free is an absolute fad. And as we discussed in the past, the truth on these controversial issues usually lie somewhere in the middle. It’s helpful to try to determine where along that spectrum do we fall and what are some helpful guidelines.
So let’s discuss a recent study. And the title was, An Italian Prospective Multicenter Survey on Patients Suspected of Having Non-Celiac Gluten Sensitivity. And this study looked to assess how common is gluten sensitivity or non-celiac gluten sensitivity. Are there any lab markers that can be helpful for determining this? What are the most common symptoms that may be associated with this? So if you’re struggling with certain symptoms, are there certain symptoms that may indicate to you that gluten may be a culprit? And what does the reaction of gluten look like in terms of how long does it take for that reaction to occur in most people? And also, are there any other comorbidities or other diseases that accompany this? So let’s jump in.
So like I said a moment ago, the sub of the study was essentially looking at 34 Italian centers. And when all these centers amass their data, they had looked at 12,225 patients. So this is a fairly impressive size of a sample. Now, the one thing that is not great about this study is the method of diagnosing the non-celiac gluten sensitivity. There is currently no lab marker to diagnose non-celiac gluten sensitivity. However, there’s a couple that are suggested that we’ll getting to in a minute. But the gold standard is elimination, take gluten out of your diet. And then perform a placebo-controlled reintroduction, meaning, you don’t know if you’re taking a capsule of gluten or a placebo capsule and then have someone monitor that. It’s very hard to do that.
So what they did was a comprehensive—essentially, a 60-point questionnaire that was administered by physicians who specialize in this area, looking at all this data collectively. So, it was a very thoroughly thought out questionnaire administered by professionals in the field. Is that a perfect measure? No. But this is some of the best data that we have here.
So let’s look at these symptoms that were the most commonly associated with non-celiac gluten sensitivity. And I’ll put a chart from the study up here in the screen. As you can clearly see that—first let me say just as a preface, we’re getting two different aspects here: There’s digestive symptoms and non-digestive symptoms. That’s important to understand because—and this is something I try to continually bring up—You can have something like fatigue or depression that’s caused by your gut, yet you don’t have any gut symptoms like bloating or constipation or diarrhea.
So it’s very important to mention because sometimes people—because they have no digestive symptoms, but only have things like fatigue and insomnia as well as other examples, think that they don’t have a problem in the gut. But in some cases—in many cases, I would argue, that a problem in the gut is actually the culprit of those symptoms.
So looking at digestive symptoms, specifically—as you can see here from the chart—bloating, abdominal pain, and diarrhea were the three most common symptoms. But there was a number of these listed. That shouldn’t really be surprising. If you’re eating a food that is inflammatory to you or that your body doesn’t respond well to, having digestive symptoms shouldn’t seem like a stretch. So nothing super surprising there.
But let’s move on to the extra intestinal or the non-digestive manifestations.
And what we see here is that lack of wellbeing—so generally not feeling well—fatigue, and headache were the three most common. So this is very important to mention because, again, someone could have only lack of wellbeing, fatigue, and headache or some of these other extra intestinal symptoms and not have any digestive symptoms and actually have a problem in their gut and, in this case, gluten sensitivity being the culprit. So it’s important to keep that in mind.
Now, here’s what I think is a very important piece, the time to reaction. Over 90% of subjects experience a discernible reaction within 24 hours. This, in my opinion, is very helpful. Why? Because sometimes you get the recommendation that if you are non-celiac—and again, this applies for non-celiac—if you’re non-celiac gluten sensitive and you consume gluten, you might be up regulating these inflammatory pathways or fueling an autoimmune process and you may not know that you have a reaction to gluten for months or for even years.
And so people are, essentially, dogmatically indoctrinated in the thinking that they should avoid gluten even though there’s no discernable reaction to gluten, which is an understandable posit if we’re trying to help someone, I get it. However, this study, which is fairly impressive in the rigor of its documentation, shows that over 90% of subjects experienced a reaction within 24 hours. So what that means—and this is something that I’ve been saying for a while now—it’s important to find your own truth in terms of how your body reacts to gluten. And if you perform an elimination and then a reintroduction and you don’t notice anything, there’s an extremely high probability, if you don’t notice anything within 24 hours, that you’re not gluten sensitive. You don’t have to worry about the rigor of eating gluten-free.
Now, if for whatever reason you want to generally avoid gluten, okay, that’s your prerogative. But at least you now know that the likelihood that you’ll have a non-celiac gluten sensitivity issue is very minimal.
Okay. So, now, it’s important to contrast that with the fact that for celiac patients, it may take weeks and maybe even a little bit longer for the symptoms to manifest. And so this is where getting the diagnosis of celiac disease can be helpful. Sometimes the argument is made, ‘Well, I am not going to eat gluten no matter what, so what’s the point of having a celiac diagnosis?’ Okay, understandable. However, if you’re someone that wants to be able to occasionally partake in gluten or if you make gluten consumption something that’s habitual, then having this diagnosis can be helpful, the diagnosis of celiac. Because for someone with celiac, the symptoms may not be apparent and they may take weeks to onset and you may have a very difficult time sussing out if it’s a reaction of gluten or if it’s because you’re tired or stressed or what have you.
So a couple of guidelines here, if you perform the HLA-DQ2 and DQ8 gene testing and that comes back negative, that fairly definitively rules out celiac. So if you have that gene testing that’s negative, that fairly definitively rules out celiac. And you can proceed under the assumption that if you have a reaction to gluten, you’d have that reaction within 24 hours. And if you do have that reaction, you can pseudo kind of diagnose yourself as non-celiac gluten sensitive. And if you don’t have that reaction, you don’t have to worry about the rigor about the gluten avoidance.
Now, if you’re positive for that HLA-DQ2 and DQ8, it is not diagnostic of celiac disease. However, it’s suggestive that it’s a possibility. So you may want to have further evaluation to rule it out. And yes, that does require people to consume some gluten. However, in my mind, it depends on how you’re approaching this. If you’re someone who has no problem avoiding gluten and you’re not planning on consuming gluten ever, then you don’t need to worry about going through this diagnosis. If you’re someone that wants to be able to eat gluten occasionally or even regularly, then consuming gluten for a few weeks—usually, the recommendation is for about six weeks—and then having the testing, wouldn’t be a bad idea to rule this out. And that also depends on the reaction. If you already know you have a fairly strong reaction to gluten, then you may not necessarily go through the rigor of firming up the diagnosis. If you’re not sure, this can be helpful.
Okay. I should also mention as a quick aside, this information is taken from the February edition of our clinical newsletter, the Future of Functional Medicine Review clinical newsletter. It’s a monthly publication that I put out that reviews very important and clinically impactful studies like this. So if this is information that you’re finding helpful and you’re a clinician, I’d invite you to subscribe and you can go over at drruscio.com/review to learn more about that. We’ll also put the link in the notes. And if you’re a layperson that’s more advanced in your understanding then this is something that is fair game for you also. Okay, so continuing on.
Associated disorders Trusted SourcePubMedGo to sourceincluding autoimmunity Trusted SourcePubMedGo to source. IBS and food intolerances were the most commonly associated disorders with non-celiac gluten sensitivity. So it doesn’t really give us anything too surprising there. However, autoimmune disease was detected in 14% of cases and two-thirds of these cases were actually autoimmune thyroid. Now this runs counter to two previous studies that found the incidence of autoimmunity in non-celiac gluten sensitive patients was actually fairly low. This finds a relatively higher correlation. And also, 18% of cases with non-celiac gluten sensitivity had a relative who was celiac. And here I’ll put up a chart essentially that is showing you the comorbidities or accompanying disorders. IBS, food intolerances, allergy, autoimmune disorders, two-thirds of that was autoimmune thyroid, and then eating or behavioral disorders.
Okay. So coming back to testing this for a moment, we mentioned that HLA-DQ2 and DQ8, here’s something else that was very interesting from the study. They found that anti-gliadin antibodies, the IgG fraction specifically, was found in 25% of patients. So that could be very helpful. If you test negative for the gene test, the HLA-DQ2 and DQ8—it’s available at most major labs—if you’re negative for that, then that rules out celiac. And if you’re positive for this anti-gliadin IgG antibody, then it’s suggested that you could have non-celiac gluten sensitivity. It’s not definitive but it’s the best marker that we have, to date.
But also keep in mind that IgG anti-gliadin antibody is not diagnostic in and of itself because it can’t indicate other disorders are present. They also found that intestinal biopsy was positive in about 30% of cases having a Marsh 1 classification, meaning, there’s not enough inflammation that’s visible in the intestines after biopsy to diagnose someone as celiac. However, there is enough to be noted as not being normal. And also they found that there was—and nothing terribly surprising here—but low ferritin, low folic acid, and low vitamin D were fairly commonly documented.
Okay. So what about the prevalence? Because this is important, right? Because, again, this comes out in the issue of, is this a BS fad that happens in no one or is this something that affects a overwhelming majority of the population? Again, coming back to that spectrum and the extreme endpoints.
So, essentially, what they found here—I’ll put the chart up on the screen—they found that in patients with symptoms who are not well and reporting to a doctor’s office, there was just over a 3% prevalence in the population. And in non-ill patients or the general population, said another way, there was just over a 1% incidence in the population. So essentially making this slightly more common than celiac disease. So is it common? Yes. Is it highly common? According to this study, no.
And, again, if this is something that you—I wouldn’t say disagree with. But if you’re finding a little bit of dissonance when you hear this, remember that this is based upon some of the best data that we have to date, right? Over 12,000 patients surveyed by doctors who are really looking for this and found this kind of prevalence. So it’s just important to factor this in. It’s not to say that if you’re listening to this or watching this and you know that you have a negative reaction to gluten, that that’s not true for you. It’s just important to keep this in mind in a more global perspective that it may not be the case for most people.
Okay. So, additionally, and this is kind of one of the points I’m alluding to, some double-blinded studies have found that the prevalence of non-celiac gluten sensitivity can be anywhere from 0.1% to 10%. So there can be a tenfold variation or 1% to 10%. In some of these studies, there’s a—I guess that would even be a hundredfold variation.
So this study, what this study adds is the sample size being so large and the diagnostic survey being so comprehensive, that gives us what is probably a fairly accurate measure in terms of 1% general population, 3% in those who are ill. And this is also very interesting. Thirty percent of cases had a unresolved issue in the gut that might be contributing to the symptoms that a person is attributing to gluten reactivity. And most specifically, they found that some of the underlying GI issues could be small intestinal bacterial overgrowth or other food intolerances, and a low FODMAP diet maybe a very helpful way of sussing out some of those other food intolerances. And that has also been published.
So again, remember, if you think you have non-celiac gluten sensitivity, you have a 30% chance to eliminate that reaction that you’re experiencing by looking into something like SIBO and/or trying a different diet like the low FODMAP diet, which can be very helpful and very empowering for some people.
So the author’s conclusions, ‘This prospective survey shows that non-celiac gluten sensitivity has a strong correlation with female gender and adult age. Based on our results, the prevalence of non-celiac gluten sensitivity seems to be only slightly higher than that of celiac disease.’ Okay?
A lot there, let me just give you a few of my takeaways. And let me say one thing, actually, before I do that, remember that they were making this diagnosis via a survey. And a survey has likely the highest potential of over-reporting. There is a potential that it could underreport. But the reason why this may over-report is because people maybe eating other food stuffs. Most mainly it could be when people ingest FODMAPs. And many wheat-containing products or gluten-containing products are found in wheat products, do also have high FODMAP. So some of that reactivity that we’re seeing when people say, ‘Yes, I reacted to gluten’, that maybe the FODMAPs they are actually reacting to and not the gluten. For some people it could solely be the gluten, yes. But for some of those people, it could be FODMAPs. So what we may be seeing here is that the incidence of the non-celiac gluten sensitivity that was found in this study may be slightly over-reported. So it’s just a caution there.
So the summary points. Non-celiac gluten sensitivity may impact roughly 3% of at-risk populations and 1% of the general population. A reaction upon reintroduction will occur within 24 hours in over 90% of cases, very important. Non-celiac gluten sensitivity can manifest as both gastrointestinal and extra, meaning non-digestive symptoms like fatigue, headache, and not feeling well. HLA-DQ2 and DQ8 testing does not appear diagnostic for gluten sensitivity, however, the anti-gliadin IgG antibodies may be.
And if someone does have the HLA-DQ2 and DQ8 positive, that is suggestive of celiac disease but not diagnostic of celiac disease. And 30% of those with gluten sensitivity may have another underlying gut issue that when resolved, would ameliorate their reaction to gluten. Most namely, it could be small intestinal bacterial overgrowth or potentially other food allergies or intolerances like FODMAP sensitivity. And placebo may be responsible for some of these cases of non-celiac gluten sensitivity. And non-celiac gluten sensitivity may be associated with autoimmune conditions in about 14% of cases, namely that may be autoimmune thyroid disease.
So there is a lot there. Hopefully, this information helps you navigate the landscape of gluten sensitivity. Because there are two things that we want to balance, just to kind of bottom line it, we want to make sure that if you have a problem with gluten, you identify that and you avoid gluten, important. We also want to make sure that if you don’t have a problem with gluten, you’re not indoctrinated into thinking that you do and you essentially make your life more difficult because you’re trying to avoid a food that you don’t actually need to.
So, again, if you’re a clinician, then you can see this full write-up with all the notes and supporting references in our monthly publication, the Future of Functional Medicine Review. You can go over to our website, drruscio.com, And if you go to the /review section, you’ll go right to the page with more information.
And so hopefully this information helps you navigate this and truly helps you to get healthy and get back to your life. Thanks.
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