 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 lies somewhere in the middle. It's helpful to try to determine where, you know, 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 multi-center 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? And 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 setup of this study was essentially looking at 34 Italian centers. And when all of these centers amassed 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 that it was 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 get to in a minute. But the gold standard is an 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 specialized in this area looking at all this data collectively. 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 on the screen. As you can clearly see, that first let me say just as a preface, we'll get into 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 guts, 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 other examples, think that they don't have a problem in the gut. But in some cases, and 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 you, having digestive symptoms shouldn't seem like a stretch, so nothing super surprising there. But let's move on to the extraintestinal or the non-digestive manifestations. And what we see here is that lack of well-being, 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 well-being, fatigue and headache, or some of these other extraintestinal 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 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 experienced 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 of gluten for months or even years. And so people are essentially dogmatically indoctrinated into thinking that they should avoid gluten, even though there's no discernible reaction on gluten, which is an understandable positive if you're trying to help someone. I get it. However, this study, which is fairly impressive in the rigor of its documentation, showed that over 90% of subjects experienced a reaction within 24 hours. So what that means is, 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 and 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 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, 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 even 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 of 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 of 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. Now, it also depends on the reaction. If you already know you have a fairly strong reaction of gluten, then you may not necessarily need to go through the rigor of firming up the diagnosis. If you're not sure, this can be helpful. Okay. I should also mention this 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 multi-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 to DrRuscio.com slash review to learn more about that. We'll also put the link in the notes. If you're a person that's more advanced and you're understanding then, this is something that's very game for you also. Okay. So continuing on. Associated disorders including autoimmunity. IBS and food intolerances were the most commonly associated disorders with non-serial 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. There were two previous studies that found the incidence of autoimmunity in non-serial gluten sensitive patients was actually fairly low. This finds a relatively higher correlation. And also, 18% of cases with non-serial gluten sensitivity had a relative who was celiac. And here I'll put up a chart essentially that is showing you the co-morbidities 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 just for a moment, we mentioned the HLA, DQ, 2 and 8. Here's something else that was very interesting from the study. They found that anti-gliad and 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, DQ, 2 and 8, 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-gliad and IgG antibody, then it's suggested that you could have non-serial gluten sensitivity. It's not definitive, but it's the best marker that we have to date. But also keep in mind that that IgG, anti-gliad and 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 March 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 nothing terribly surprising here but low ferrets and low folic acid and low vitamin D were fairly commonly documented. Okay, so what about the prevalence? Because this is important. Because again, this comes out of the issue of is this a BS fad that happens in no one or is this something that affects an overwhelming majority of the population? Again, coming right 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 over a 3% prevalence in the population. And in non-ill patients or in 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 won'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. 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 the gluten, that that's not true for you. I want 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-blind 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%. So there's, 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. 30% 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 may be 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. So 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 a likely the highest potential of over-reporting. There is a potential that it could under-report, but the reason why this may over-report is because people may be eating other food stuffs. Most namely it could be when people ingest FODMAPs and in many wheat-containing products or gluten-containing products that are found in wheat products do also have high FODMAPs. So some of that reactivity that we're seeing when people say, yes, I reacted to gluten that maybe the FODMAPs are actually reacting to and not the gluten. So will they 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 the 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 and 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 8 testing does not appear diagnostic for gluten sensitivity. However, the anti-glad and IgG antibodies may be. And if someone does have the HLA DQ2-8 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 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 and about 14% of cases and 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 slash review you'll go right to the page with more information. And so hopefully this information helps you navigate this and truly helps you get healthy and get back to your life. Thanks.