In this episode, we discuss:
- Dr. Asfour’s background
- Why celiac disease is often undiagnosed
- The connection between Lyme disease and celiac disease
- What could be causing that link
- If celiac disease is becoming more common
- Whether kids should eat gluten
- The rise of autoimmunity
- How celiac disease is diagnosed
Note: Chris has moved on from the California Center for Functional Medicine (CCFM) and has started Adapt180 Health™, a membership-based health transformation program that gives you the tools, the team, and the support you need to make real, sustainable, long-term changes to your health—and your life.
Hey, everybody. Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, I’m really excited to welcome my colleague from the California Center for Functional Medicine, Dr. Ramzi Asfour, as my guest. Dr. Asfour is board certified in infectious diseases and internal medicine. He graduated from New York Medical College, and then completed an internal medicine residency program at California Pacific Medical Center, followed by a fellowship in Infectious Diseases at UCSD [University of California, San Diego].
He’s worked for the World Health Organization (WHO), Columbia University in South Africa, and [UCSD]. Prior to attending medical school, Dr. Asfour majored in genetics at UC Davis [University of California, Davis]. He is currently assistant clinical professor of medicine at UCSF. And I’ve had the pleasure of working with Dr. Asfour for the past couple of years [at] our clinic, CCFM, and I’m looking forward to talking with him about a really interesting poster he presented at a celiac disease conference establishing a possible association between genetic susceptibility to celiac disease and chronic Lyme disease. So let’s dive in.
Chris Kresser: Dr. Asfour, thank you so much for being here. I’ve really been looking forward to this.
Ramzi Asfour: Thank you, Chris. I’ve been looking forward to it, as well. It’s about time we did a podcast together.
Chris Kresser: That’s right. I’ve had the pleasure of working with you at California Center for Functional Medicine for, how long has it been now since you joined us?
Ramzi Asfour: Going on the third year, so more than two years.
Chris Kresser: Ah, time flies. It’s been amazing to have your infectious disease and other expertise in the clinic, since so many of our patients are dealing with various forms of infectious disease. And I’ve really enjoyed getting to know you and working with you.
Ramzi Asfour: Thank you, likewise. Yeah, it’s been a pleasure.
Dr. Asfour’s Background
Chris Kresser: Alright, so for the listeners who may not be familiar with you and your work, why don’t you just tell us a little bit about your background both in conventional medicine and then how you switched over to the dark side and joined us in Functional Medicine.
Ramzi Asfour: Some would say, most of your listeners and myself would have it the other way around.
Chris Kresser: That’s right. That’s right.
Ramzi Asfour: So I saw the light.
Chris Kresser: You saw the light.
Ramzi Asfour: So I did medical school in New York and [an] internal medicine residency in San Francisco at California Pacific Medical Center. And then I was always interested in infections, infectious diseases, and international health. And so I went to a fellowship at [UCSD] in infectious diseases. And while there, I, of course, learned regular infectious disease practice, which for those of you who don’t know, that’s more of a hospital-based practice.
So you see some patients in [the] clinic and definitely a lot of HIV. But [you spend] most of the time working in the hospital, and then doing research. So I did research in HIV. And also clinical research and mainly in infection control, and also HIV and care projects in Africa, mainly Ethiopia and South Africa. And so, when I finished my fellowship, I worked in South Africa setting up HIV care and treatment clinics. And then, I worked at the World Health Organization in Geneva. I was basically the head of doctor training for the HIV program, and training doctors mainly in Africa, on HIV. And then, [my] family and I really loved seeing patients and the patient care. And so, when I was at the level of the World Health Organization, I didn’t have that patient touch, and that’s really what I enjoy about, especially about Functional Medicine.
So I went back to the States, all my family’s in Northern California. And so we moved back, had kids, [and] I worked in conventional internal medicine and then [in] infectious disease. So I’ve done about 16 years of infectious disease practice. But [for] the last few years of my infectious disease practice, I had a lot of patients who I couldn’t help in the conventional paradigm, [with] either Lyme disease or strange autoimmune disease. And then my daughter developed celiac disease. And it wasn’t me who diagnosed her; it was my wife, who now [is] an acupuncturist and [a] Chinese medicine doctor. But at the time, she wasn’t; she didn’t have that training. And she said, something’s wrong. And we had Kaiser, and she convinced the Kaiser doctor to do the tests.
And then we found out she had celiac disease. And so, that was the start of my journey into finding a different approach. And my own family history, as many of us have it, then my, the fact that there were a lot of patients that I could not help. And I did training with the Institute for Functional Medicine. I met Sunjya Schweig, who is your colleague at CCFM, through a mutual friend, and Sunjya and I hit it off, and we’ve been working together basically ever since. And I’ve done your ADAPT training program, as well. And now I’m really enjoying the practice of Functional Medicine. It’s very interesting. I keep a foot slightly in the conventional world. I keep some hospital privileges, and I do a little bit of infectious disease telemedicine, but my joy is Functional Medicine, and I love that patient contact and helping patients in that domain.
Why Celiac Disease Is Often Undiagnosed
Chris Kresser: Yeah, I wish the story of your wife was rare where someone has, suspects they have a gluten intolerance or celiac disease and it’s not the doctor who initiates that testing, but the patient. And of course, we’re going to be talking more about celiac [disease], but it strikes me that it’s one of the few autoimmune diseases that’s relatively easy to treat, comparatively, at least, to something like multiple sclerosis. And yet it’s still dramatically underdiagnosed.
Ramzi Asfour: Absolutely. That’s one of the major issues with celiac disease. I mean, it’s certainly, it’s easy to treat. It’s not easy to avoid gluten, for sure. So I don’t want to minimize that. But it’s not like multiple sclerosis by any means.
Chris Kresser: Yeah. And for every person who has a typical form of celiac where there’s severe enteropathy and diarrhea after eating gluten and that kind of very clear chain of causality between eating gluten [and] then having a reaction, there are 6.2 cases of atypical celiac where it might manifest as brain fog or muscle pain, myalgia, or skin dermatitis or any other type of skin manifestation. So, in the defense of doctors, it can be a very tricky, it’s not necessarily [a] disease you can always just diagnose based on the symptoms.
Ramzi Asfour: Absolutely, absolutely. And I think that my daughter’s manifestation, for example, was ADD [attention deficit disorder]. She had ADD, and she had actually lost a little bit of weight, but living with her every day, I didn’t realize. She was four years old; she should not [have been] losing weight.
Chris Kresser: Right.
Ramzi Asfour: But it was ADD. She didn’t have diarrhea that most people would complain about. So I’ve, in my practice at CCFM, I, actually, I test everybody for celiac disease now, and I think that people presenting with vague complaints, or even no complaints, I think it’s, in our population, it’s worth screening for celiac disease. Screening in the conventional world for celiac disease is controversial, to say the least.
Chris Kresser: Yeah, yeah, but in a population of people who are seeking out Functional Medicine who have complex, often very chronic, often mysterious symptoms and who are motivated enough to pursue Functional Medicine, the calculus there for me, and I know for you, is that the impact of having it far outweighs the small expense and trouble of screening for it. In other words, if you find it, it’s going to be a game changer. And if you don’t find it, it’s going to get in the way of everything else that we’re doing.
Ramzi Asfour: Absolutely.
Chris Kresser: Right.
Ramzi Asfour: Absolutely. There was even one study I was reading talking about, for screening, they were saying, well, even people who don’t have any symptoms, if they find out by a screening program that they have celiac disease, even if it’s mild, and then they avoid gluten, they will feel better. So some people might not think they have symptoms. But then after that diagnosis, and I’ve had, we, I’m sure you’ve seen that, we’ve seen this in our practice, “Wow, I do feel a lot better, and all I did was stop gluten.”
Chris Kresser: Right. Unfortunately, humans are very adaptive, fortunately, and unfortunately, we’re very adaptable. We get used to our new normal, and we don’t recognize or remember what it felt like to feel really good. I mean, the other side of that, of course, is we might, those patients might be averting onset of a disease 10, 20, or even 30 years down the line due to antibody production against the transglutaminases like TTG6 in the brain, or TTG3 in the skin, or TTG2 in the gut. And that’s something that you can’t really subjectively experience, the production of those antibodies, and the body gradually degrading microglia or something in the brain.
Ramzi Asfour: Absolutely, and not only that, it’s that the incidence of other diseases, cardiovascular disease, for example, is higher in untreated celiac disease. It’s an inflammatory disorder, and Functional Medicine is all about decreasing sources of inflammation. So you’re probably, it’s documented. I mean, there are good studies showing that you have higher rates of cardiovascular disease in untreated celiac disease. Higher rates of other autoimmune diseases, but you probably also have other rates of cancer and you have a shortened lifespan, unless you treat it.
Chris Kresser: Sure. Sure. Yeah, I mean, pretty much all modern chronic disease that we, is inflammatory in nature. So the ones, the diseases that we know there’s an association with are just the ones that have been studied. It doesn’t mean that [for] others, there isn’t an association. Lack of evidence is not evidence against, right?
Ramzi Asfour: Absolutely.
Chris Kresser: So you recently went and spoke or presented a poster at the International Celiac Disease Symposium along with Laura [Montgomery], you mentioned, and Nick Waring is a former patient and now [a] student in medical school. So, tell us a little bit first about this conference because it’s an interesting conference, and then we can go into your poster.
Ramzi Asfour: Okay. So this is the International Celiac Disease Symposium, which is the largest celiac disease conference. It happens twice a year, sorry, every other year. And the last time was actually in India, and I’ll get to that later. You might think there’s no celiac disease in India, but it’s not true. And it’s a group of very, very dedicated researchers, and a few patient advocacy groups who are really trying to solve issues, solve problems around celiac disease in terms of everything you can think of. Diagnosis.
Why are the rates of celiac disease going up? They’re asking questions of what can you do to treat celiac disease. It’s a very interesting group of people there. Some are food scientists. They’re looking at wheat and has that changed and is that a trigger. What in our food system is an issue? And so, there’s a lot of really good, a lot of really good science going on there.
Chris Kresser: And were there any other functionally oriented people there, or was it pretty much 100 percent conventional medicine?
Ramzi Asfour: Yeah, sadly, to my knowledge, I was the only Functional Medicine person there. I mingled with a lot of people. And I speak French, so I was speaking to some of the people [because] it was in Paris. So there were a lot of people from France, and I didn’t find anybody who was Functional Medicine-oriented except for a few patient advocates that were there that knew about Functional Medicine.
Chris Kresser: Did you get any blank stares, or worse, scowls of recognition about Functional Medicine?
Ramzi Asfour: Well, to be honest, I was very careful of what I said. I did ask a lot of questions during a lot of the scientific sessions. But my goal was more to learn from them. I knew that changing their approach on this is not, it’s not going to be a one-man show …
Chris Kresser: Yeah, absolutely.
Ramzi Asfour: … to do that.
Chris Kresser: It’s interesting. As a total side note, I found the awareness of Functional Medicine in Scandinavia is really high. We both have a colleague and friend in Sweden, and there are many others. I’ve spoken, traveled to Stockholm, and presented there. And it’s also very high in the UK. But on the continent, the continent is really, really lagging behind in Functional Medicine awareness. I’m not sure why that is.
But I’ve had a number of doctors that are aware there complain to me about that. So, yeah, tell us a little bit about your abstract and study, because I think it’s fascinating and certainly could lead to some interesting avenues of further research.
Is chronic Lyme disease connected to celiac disease? It’s possible, and in this episode of RHR, Dr. Ramzi Asfour and I discuss the reasons why. #functionalmedicine #chriskresser
The Connection between Lyme Disease and Celiac Disease
Ramzi Asfour: So we, I test everybody for celiac disease and for Lyme, and I’ve noticed that a lot of people test positive for Lyme disease that also have a really high celiac genetic risk. So, when I test people, I have an unconventional approach, as you all might imagine, of testing people for celiac disease. I test them, I test everybody for celiac genetic risk. That is not what we’re supposed to do according to normal guidelines.
Chris Kresser: The algorithm.
Ramzi Asfour: Right. But I do that for several reasons. I think that it’s important to know your genetic risk, and a lot of our patients are already on a gluten-free diet, or they’re eating small amounts of gluten or maybe trace amounts of gluten. So it’s, it really is important to know their genetic risk. And then I will test their antibodies, TTG, but also the anti-mycelial antibodies, and I’ll do IgA [immunoglobulin A] and IgG [immunoglobulin G] testing on most patients through a panel at either LabCorp or Quest.
My preferred panel at the moment is at LabCorp, but that changes from time to time. But I also noticed that a lot of the patients testing positive for Lyme are, they have a high genetic risk for celiac. And so, I wanted to study that connection in more detail. And so, we did an analysis, Laura Montgomery at CCFM and I, and also Nick Waring helped in analyzing all of our patients from any of the providers that are presented to CCFM. And we found that [of] about 41 patients that had a high celiac genetic risk and the test for Lyme, 24 of those had significantly positive tests for Lyme disease. And then if you add in …
Chris Kresser: And that was using the CDC [Centers for Disease Control and Prevention] criteria, to be clear.
Ramzi Asfour: Correct.
Chris Kresser: Which are well-accepted.
Ramzi Asfour: Exactly, that was using CDC criteria. If you’re a little bit looser and use an ELISA [enzyme-linked immunosorbent assay], or non-CDC criteria, we would have 68 percent of those testing positive for Lyme. And we know from experience that a lot of our [patients with] Lyme [disease] feel better when they’re off gluten. And there’s a lot of reasons that people with an inflammatory disease or an infection might feel better off gluten. But the correlation between high celiac genetic risk and a positive test for Lyme disease was very interesting to me. And so, I really wanted to put that out there in the scientific world.
And we wrote this poster as a starting point of perhaps doing more studies and involving more researchers in answering this question. And I developed a connection with a scientist, Dr. Taylor, who’s the one that actually has done a lot of studies on celiac genetic risk. And we might be interested in performing some more studies and querying large databases of lab tests that have already been done to see what we can learn from that data. It’s a very interesting field, a very interesting association. It leads to a number of questions, too:
- Is it that the patients with a high celiac genetic risk will be sicker from Lyme disease if they get it?
- Are they more susceptible to Lyme disease?
- Are some of these patients having false positive tests for Lyme disease? Or what is out there?
And we really don’t know, and to be honest, like in a lot of things in medicine, it’s probably not one thing. It’s probably, some patients have had, and some of the patients that I’ve seen and treated, we looked at 10 of them in more detail. We take away the gluten, and they feel better, and some of them, they’re pretty sick. So we take away the gluten and we treat Lyme, and then they feel better. And in some people, we just treat Lyme [disease], and for other reasons, they weren’t able to take away the gluten. For example, one of them was a chef, and [that] makes it difficult. Livelihood depends on cooking in a non-dedicated gluten-free facility. So there are caveats. It’s an interesting field.
Chris Kresser: Yeah, it’s so fascinating. I mean, I was, when you first gave that and shared the results, I was thinking a lot about what the various mechanisms might be in both directions. And we, as you said, we often have a tendency to want to pin it down to one factor, create a one-way kind of linear chain of causality. But it’s so often not how it works. It’s much messier, and almost, if you look at the diagram behind your head that we created for CCFM, that’s probably a better visual representation of what’s going on.
But I’d be curious [as to] what you think. I’m sure you’ve thought a lot about this, too. And we obviously don’t know the answer. And in science, you’re often not encouraged to speculate. But I’m going to encourage you to speculate. And what do you, what’s your gut sense, pun intended, of what might be happening here?
What Could Be Causing That Link?
Ramzi Asfour: Well, I think that, I think that there is probably some merit to the idea that people with a high celiac genetic risk would be more susceptible to Lyme disease. And I think, or at least the chronic manifestations of Lyme. I do think that that’s, that plays a role. And it’s very, celiac genetics are somewhat complicated. It’s not just the two genes; we call them HLA DQ2 and DQ8.
And if you have, if you don’t have those genes, you’re probably not going to get celiac disease. You can still get chronic Lyme disease. But if you have those genes, perhaps you’ll be, if you get a tick bite and you develop Lyme disease, perhaps you’ll be more susceptible to getting the chronic manifestations. My gut sense is that that’s what’s going on.
Chris Kresser: So, clarifying question. Do you think it’s the genetic disease risk that is responsible for that association? Or do you think it’s the untreated celiac itself and the manifestations of that, like the inflammation, the inflammatory milieu that is responsible?
Ramzi Asfour: Very difficult to say. And I think that they’re probably both playing a role. That you can’t separate one from the other. But some of these patients probably do not have celiac disease. I don’t have biopsies on all of them to say for sure. And as I mentioned, a lot of them were already on a gluten-free diet.
So it’s difficult to say definitively if they had celiac disease, but some of them probably did not have celiac disease, and they have just the genetic risk, and they still have the chronic manifestations of Lyme. But let me clarify something, that 30 percent of people of the American population carry DQ2 or DQ8. So 30 percent of that population has a risk for celiac disease. I didn’t just use that risk, however. I tried to narrow down that population to the ones that have a higher risk. So, I probably, the genes that I used in my study probably represent fewer than 10 percent of the American population.
So I was quantifying the celiac risk, depending on which specific, they’re called haplotypes. But which specific genes, if you will, or alleles that our patients had, and I was using the higher-risk ones. So there is probably something in both directions.
Chris Kresser: Okay, that’s good to know. And you stratified the risk further, and we’re choosing those that were at the highest risk. And what do you think it is about DQ2 and DQ8 or that high-risk haplotype? Like, what is it that those genes are doing? What proteins are they coding for, expressing, that would put somebody at higher risk? Or is that just too, we have no idea at this point?
Ramzi Asfour: Well, so, they’re human leukocyte antigens [HLAs]. So they’re in the HLA genes; you might have heard about that for typing for transplants. So when you have a kidney transplant, you have to have an HLA match, for example. And so, there are antigens on human white blood cells or leukocytes, and they are responsible for T cells.
So, the T cell response is, we also call that the cell-mediated immune response, is one of the major parts of the immune system that plays a role in celiac disease. And one of the interesting facets here is that they help. I mean, it’s involved in T cells, and T cells are involved in your memory response. So, these T cells, once they become activated against gluten, and we don’t know exactly how that works, but we have some ideas, they store that memory for a long time. But it’s not that they code for specific proteins like some other genes that you might think of because these are in the HLA; these are HLA genes.
So they’re, we have to think about them slightly differently. And then another interesting facet is that if you use 23andMe, for example, or one of the online genetic testing services, they test for SNPs, or single-nucleotide polymorphisms, and SNPs test for differences in genes. But some of the SNPs don’t, you can’t test all the HLAs through SNP. So certain SNPs, sorry, so through 23andMe, you’ll miss.
Chris Kresser: You’ll miss some people who are positive.
Ramzi Asfour: Exactly, like my daughter, for [example]. She’s had 23andMe, negative genes, but if you run the genes through a different kind of specialty lab, she does have the Q2.2. So, you can miss some.
Chris Kresser: That’s a really important point I want to emphasize because a lot of people are relying on consumer genetic tests like 23andMe to get this type of information, and it’s not always reliable. Much better, I think, to use a lab like Quest or another reference lab that is going to give us much more evidence-based reliable information on these haplotypes.
Ramzi Asfour: Absolutely.
Chris Kresser: So, let’s kind of zoom out a little bit and talk about these particular haplotypes. What do we know about when they arose? Why may they have arisen? Because certainly, if there is a genetic thing that has been preserved in the population for a long period of time, it must have had some original. I mean, certainly there are spontaneous mutations that occur, but if it’s persisting for as long as it is, why is that?
Ramzi Asfour: That’s interesting. And there was some talk about that at the conference. It’s not to probably protect against certain infections. But we don’t know that to a high degree of certainty. We think that there has to be some evolutionary utility to having this. And malaria and sickle cell disease, for example. That’s very clear.
Chris Kresser: Yeah.
Ramzi Asfour: Sickle cell protects you against malaria.
Chris Kresser: Malaria.
Ramzi Asfour: So that’s why it’s a deadly disease. But in celiac disease, it’s a little less clear. It’s not well understood why 30 percent of the population, and this is probably of the world, has genetic susceptibility to this disease.
Chris Kresser: Yeah, and I know, [for] hemochromatosis, there’s a similar theory that people who increase survival rates during the bubonic plague in medieval Europe. And so, a large percentage of people who survived had those, had the genetic, they were either carriers or homozygotes for those mutations, C282Y or H63D. And then they, because the population shrank so dramatically, and those, they became sort of the founding population for our ancestors, basically.
Even though, of course, hemochromatosis increases the risk of dying from other infections, it would have conferred a protective effect there. So it’s really fascinating to me to think about these things, even though they’re not necessarily directly relevant to what we’re going to do about it. Let’s move on to something a little more practical, maybe, which is just this growing incidence of celiac disease. What are the latest statistics that you heard, if they covered that at the conference, in terms of prevalence both in the [United States] and worldwide? Is it increasing? Do we have solid evidence of that?
Is Celiac Disease Becoming More Common?
Ramzi Asfour: We do, we definitely have solid evidence of it increasing. And in the developing world, it tracks to increasing wheat consumption pretty nicely. So, take, China is a good example wherein at least we have thought traditionally that people of Chinese ancestry don’t have a high risk for celiac disease. But if you look in parts of China, and you can use the Yangtze River to cut China into North and South. And in the north, they can’t grow rice, because rice needs more temperate weather. But wheat grows pretty well.
And so, if you look in the wheat-eating communities in Northern China, for example, in some studies, there’s as much as 2.3 percent prevalence of celiac disease. In the [United States] and in already developed countries, we’re not eating more wheat than we used to; we’re eating about the same. And so, why do we still have in the [United States] an increasing problem with celiac disease or increasing incidence and prevalence of celiac disease? And there is no good answer. There was one interesting study, and we always ask, is it the wheat that’s changed? What are the options? Is it the wheat? Is it the pesticides or other toxins? Is it, they actually use microbial transglutaminases as food additives that you don’t necessarily have to declare on the product label except if you’re in Switzerland.
And those have been more common, and also another thought is vital gluten. Vital gluten is an additive that is put into some commercial bread products, for example, to make them gooier and make them taste better. But the question of has wheat changed was addressed specifically. The other questions were not [addressed] at the conference, and there was a very good study in Germany that looked at wheat cultivars from 1890 to 2010. And they went into enormous detail here. And I’ll spare you all of that detail because it’s excruciating, and an excellent study.
And these are food scientists that did this. They did it without pesticides, without fertilizers to mimic the same conditions that were present as early as the early 1900s. And they did not detect a significant difference in gluten content over the most common cultivars of wheat, the most recent decades versus the earlier decades. So probably, according to them, at least, and in Europe or in German wheat, there isn’t a huge change in the gluten concentration.
Chris Kresser: Did they compare European wheat to American wheat? Because I know you’ve heard this before from patients where we have patients who go to Europe and eat wheat there and have a totally different response to the wheat in the [United States]. And of course, that could be many things. They’re on vacation; their stress is lower. But could it also be that the wheat that’s being used in Europe is qualitatively different than the wheat in the [United States]?
Ramzi Asfour: I see that a lot that patients in, here, as you said, Chris, that will go to Paris and they’ll eat a baguette, and they’ll have no problem. And then they’ll do the same thing in the States, and they’ll have a problem. And I can speculate a lot, and are they putting additives in our bread? I always tell a story to my patients like this. You can take a baguette that you get at 9 a.m. in Paris, and you can take it to the baseball stadium (not that they play baseball there), but you could probably hit a home run with it.
Chris Kresser: That’s right. It’s hard as a rock.
Ramzi Asfour: Exactly. But the same baguette that you buy at your local Whole Foods would still be soft at 5 p.m. Now, why is that? I’m not an expert in that, exactly. But are there, are they using additives like microbial transglutaminase? Are they, that will actually increase shelf life and make the bread stickier? Are they using other preservatives? Is it that we use pesticides or herbicides on our wheat crops? Some people say that, and some farms probably do use some glyphosate to make the wheat germinate a little bit more quickly. So it’s a complicated question. But also one other factor that we have to think about is, what’s the state of your nervous system when you’re in the [United States] versus on vacation in Europe, right?
Chris Kresser: Absolutely. Yeah, I think that’s a big factor that’s often underappreciated.
Ramzi Asfour: Right. So, some foods might have, they might require more energy to digest, if you will. And if you’re in stress mode, work, work, work, and you eat some gluten in the States and you don’t have celiac disease, you might feel more of an effect than [if] you’re totally relaxed on vacation, eating at the beach in the Italian Riviera and you have a sandwich or a fresh baguette there or something, you might not feel the same effect.
Chris Kresser: And that’s not just true of wheat; that’s true of a lot of foods that people react to I’ve seen with my patients, and even things like alcohol and caffeine. Like, people can have a triple espresso in Italy while they’re on vacation and feel fine, but they do that at home when they’re in the course of their normal life and stress levels are high, and they feel like they got plugged into a socket. It’s a totally different story.
So let’s talk a little bit about pediatric, well, kids. So, let’s say you’re a parent, you have a very young child, you’ve got a baby or you’ve got a two-year-old, and they’re just about to start eating. And you’ve heard these conflicting reports about whether you should sensitize your kids to allergens like peanuts and maybe, like, gluten, should you feed them a little bit of gluten to reduce their, potentially reduce the risk of celiac and gluten intolerance? Or should you just avoid gluten until they’re older and their immune system is more developed? You mentioned already that in some of these other places, eating more gluten is associated with higher incidence of celiac disease. So where do you come down on this whole question?
Should Kids Eat Gluten?
Ramzi Asfour: Well, it’s interesting. And there were a few studies looking at the, at that question, even during pregnancy. And this is one of the reasons I like to know a patient’s celiac genetic risks. So, if I have a patient who comes to see me and she wants to have a baby, one of the tests I would include would be celiac genetic testing for her and her husband. So that way, I’ll know if there’s a potential for celiac disease in the baby.
And that way, we can counsel the mother because this is one thing that seems relatively clear in the literature, that even if the mother is breastfeeding and eating gluten, and the baby is not eating anything except breast milk, that can be a risk factor for celiac disease in the susceptible baby. So, if the baby has genetic susceptibility, let’s just say, for example, that the baby’s dad has celiac disease, and the mom doesn’t have the genetic risk. If the mom eats gluten, and the baby got the genes from dad, then the baby is at higher risk of celiac disease, even if the baby’s only eating breast milk. And so, that risk also translates to when foods are introduced. It’s about the quantity of gluten consumed, perhaps more than the actual time of introduction over the long haul.
So I think that that is a very interesting field, and yeah, in adults and children, it does seem to be that the time of introduction isn’t maybe as important as the amount of gluten. However, in one study in Italy, they assessed in children if a child has a genetic risk for celiac disease, when do you need to stop testing them? So, if the child had a test at four years of age, then they were not very likely to get celiac disease later on in childhood. And certainly, if you test that child at nine years of age, they had almost no risk of developing celiac disease in childhood. And the pediatric guidelines say you can stop testing the child there forever.
But the adult guidelines, and this is a very interesting part that needs future research, we know in adulthood that there’s another peak; there’s another group of these patients that develop celiac disease in adulthood. And why is that? And so, we can’t just stop screening, and probably, cumulative gluten intake is important. But in a child, if you get to six years, or certainly nine years of age, and you don’t have celiac disease, even though you have a risk, you’re not likely to develop it, at least until early adulthood.
Chris Kresser: That’s fascinating, and I imagine will be a bit of a relief to some parents who are struggling with the question of, “Oh my God, if I feed, if my kid has a tiny bit of gluten, are they going to develop celiac as a result of that? And on the flip side of that, do I need to be, like, methodically giving, titrating gluten exposure with my kids?” It doesn’t really seem to work that way from the research that we have now.
Ramzi Asfour: Right.
The Rise of Autoimmunity
Chris Kresser: So, let’s talk a little bit about any other, what do we know at this point about, I kind of want to rewind and contextualize this in the question of why is celiac prevalence increasing? It’s not just celiac prevalence that’s increasing, it’s all autoimmune disease, right? We now have 80 autoimmune diseases [that have] been identified, or 90, and that number is growing every year, and the rates of all kinds of autoimmune diseases are going up. And it seems to me that there’s something some, my theory is it’s some combination, of course, of modern diet and lifestyle and then the impact that has on our gut.
And then, the gut and intestinal permeability as Alessio Fasano has argued, being an important precondition in the initiation of autoimmune processes. So, if someone does have, let’s say you work with a pregnant woman, you do testing, you find out that she and/or her husband is at a high genetic risk for celiac, and therefore, their son or daughter is going to be, as well, how would you counsel them to prevent that haplotype from expressing? What are the things that are important for them to keep in mind, both for themselves and for their children?
Ramzi Asfour: So, one of the big takehomes, just taking it another step back from the conference, especially on the conventional side, is that you don’t want to limit a person’s diet if you don’t have to. And I think that’s also what we believe in, in Functional Medicine. You don’t want to limit a person’s diet, if you don’t have to. However, we know that certain things are inflammatory. And there’s some component here of eating for your genes, like eating for who you are culturally and what your genetic background is. And so, we also have to think about eating in quantities and processed foods and not processed foods. And so, in this couple, where they both have a high genetic risk, yeah, I would try to find out if they’re, if they feel better off gluten or not. And I would say if they say, “Well, I feel much better off gluten, even though I don’t have celiac disease, but I feel better off gluten, I’d rather eat Paleo. Or I’d rather eat a Mediterranean Paleo diet or something, but I just avoid gluten,” then I would advise them to, since that’s how they feel better, their child will probably be similar, then they should avoid gluten. But they don’t necessarily need to limit gluten in the child.
So I would have the child tested for celiac genetic risk. LabCorp, for example, can run a specimen off of a cheek swab. So you can do this on a baby without drawing blood, which is great. And so, once the baby’s born, you’ll know that baby’s genetic risk, and we’re going to assume it’s high. So then, it’s a matter of what the parents feel best. There’s no right answer, first of all, and we’re going to screen that baby for celiac disease once a year with a blood test if they do have that high genetic risk. That would be a strong recommendation.
So while we’re doing that screening, the baby will be seeing a pediatrician and getting regular checkups. If anything is amiss, then definitely that baby should be off gluten and probably have a biopsy to look for celiac disease at that time. But assuming not, I would say let the baby stay in your gluten-free house, but when the child is old enough to go to parties, if they want a cupcake that everybody else is having, let them have that cupcake. I have a child who can’t have that cupcake. And it differentiates the child; they’re not part of the pack, [and] there’s a social and behavioral cost to avoiding gluten in social context. It can be isolating for a child who doesn’t understand the dynamic.
Chris Kresser: Yeah. Our daughter Sylvie is, has a mild gluten intolerance. She [doesn’t have] celiac; it’s more of a quantity thing with her. Like, if she eats a lot of it, we definitely notice things. But we’ve tried, if she goes to a party, I mean, in the Bay Area, often when you go to a party, there’s gluten-free, dairy-free, vegan, raw, whatever. So it’s not as much of a concern. But in many, in some cases, we go to parties and there isn’t. And we tend to let her have that for that exact reason, even though it’s probably not optimal and she probably has some mild reaction, in our calculus, it’s been, like, the benefits of her just being able to do that and not see herself as someone who has that issue is, everyone has to make their own decision with that. But I agree that there’s definitely a cost there to consider.
Let’s talk, we’re getting to the end of our time here. But I want to, and we could, we’ll definitely have you back because there’s so much more to cover on this subject. We’re really just scratching the surface. But let’s finish with diagnosis because that’s, if someone is wondering and listening to this if they have celiac disease, in addition to the HLA DQ genes we’ve been talking about and the genetic susceptibility, what about actual markers that confirm or rule out celiac?
How Celiac Disease Is Diagnosed
Ramzi Asfour: So the standard marker is the tissue transglutaminase IgA. That’s the most accepted marker worldwide in terms of diagnosing celiac disease. And if you did tissue transglutaminase, submarkers it’s tTG-IgA2 or tTG2-IgA, that’s the marker that, if that’s more than 10 times the upper limit of normal, then most people worldwide agree that’s celiac disease. And if you have the genetic risk, that can clinch the diagnosis without having to do a biopsy.
So let me take a further step back that before you decide to go on a gluten-free diet or before you commit to a long term gluten-free diet, at least think about speaking to your doctor about getting a test for celiac disease. Because if you think that gluten, [you’re] going gluten-free and you have some gut symptoms, or as Chris mentioned, a lot of the symptoms are not gut-related. They can be multiple, multiple symptoms from fatigue or ADD, to neuropathy, to arthritis, and [so] on. But if you’re going to stop gluten, you need to think about getting a test for celiac disease. And most doctors will order a tTG-IgA. I will order a much more comprehensive panel, including tTG-IgG, and the mycelial antibody, as well.
Chris Kresser: I think what Mayo Clinic is using as a screening marker now and a mycelial antibody.
Ramzi Asfour: That has a very high specificity for celiac disease, and it can be used as a confirmatory test if you have questions. The interesting thing here and the new science, the new developments are coming out, and what do we do with our patients who are on a gluten-free diet and we think they might have celiac disease, but it’s actually quite important to know if you have celiac disease. And so, how do you make that diagnosis?
Well, the good news is that there are two different lines of tests that are in clinical trials that are hopefully going to come out soon. And I’m talking to one of the companies trying to get some patients enrolled, so far without success. But there are two methods of looking at, here’s a quick gluten challenge. I’m going to give you a standardized dose of gluten in this standardized cookie. You eat the cookie. I’m going to do blood tests right before you eat the cookie and right after you eat the cookie. And if your levels of inflammatory markers in the blood go up, then that’s celiac disease. And so, and that can correlate to a high degree of certainty, whether you have celiac disease.
There’s another method of testing. They’re called HLA tetramers. It’s kind of confusing science, especially to me, and I have spent some time trying to figure that out. But HLA gluten tetramers. And a similar thing, those can test for those memory T cells that we talked about before, to see if you have any of those memory T cells to gluten without having to do any gluten challenge or just a limited gluten challenge. And that’s two lines of testing that will hopefully be on the market, I’m guessing in early 2021 or 2022. So we’re a couple of years away from that. In the meantime, if you’re already on a gluten-free diet, in this country, there’s no great way to test except by doing a formal gluten challenge.
Chris Kresser: Without a lot of pain and suffering if you already know that you are gluten intolerant. Yeah. And I understand that in a lot of places, biopsy is being avoided in kids, as well, because of the invasive nature of that procedure.
Ramzi Asfour: Right. And that’s also, diagnosing celiac disease without a biopsy, if you have very high levels of tTG-IgA, is probably okay. But in others, you should probably do the biopsy. In my daughter, she had very high levels of all the markers, and her tTG-IgA was about 20 times [the] upper limit of normal. So very high. And there was no question. She had weight loss. There was no question. We did not do a biopsy.
But we’re very strict on gluten avoidance, and we can talk about gluten avoidance and what a celiac diet looks like, at least to me, later. But the, I’m thinking of going back and doing a biopsy just to confirm. My take is that if there’s any residual abnormality in a child or adult who had celiac, is on a gluten-free diet that’s very strict, and there’s still anything going on, you should do a biopsy to make sure they don’t have refractory celiac disease or some other condition.
Chris Kresser: Right. Right. Well, Ramzi, this has been really fascinating. And I think we should definitely do part two, because there’s still a lot that we haven’t had a chance to cover. And in the meantime, where can people find out more about your work and learn how to become a patient if they’re interested in getting some of this testing and figuring out if they have celiac, and then, of course, knowing what to do, if they do have it?
Ramzi Asfour: Absolutely. Go to our website, our clinic website at CCFmed.com. You’ll find our profiles. And on social media now, we’ve posted a little bit of work and the abstract that I’ve done. And feel free to contact us, and we’d be happy to consult [with] or see you as a patient, if you’re interested.
Chris Kresser: Great. Well, let’s get that part two on the schedule. I want to continue this conversation. In the meantime, thanks everybody for listening. Hope you got a lot out of this. And thank you, Dr. Asfour. And we’ll see you next time.
Ramzi Asfour: All right. Thank you, Chris.