Welcome to the Evolution of Medicine podcast! This week, we sit down with Dr. Elroy Vojdani, a preeminent functional medicine physician, researcher, and educator. Dr. Vojdani and his father, Dr. Aristo Vojdani, widely recognized as the godfather of functional immunology, have partnered to research intestinal permeability and the gut-brain axis. These are two key areas in understanding and resolving autoimmune conditions, which affect millions of patients. Dr. Vojdani shared some of his clinical findings, the strategies and products he uses in clinical care, and why his new practice will feature a meeting space dedicated to group visits. It was a fascinating 30 minutes and if you’re interested in the future of autoimmune disease reversal (and based on that growing number of patients, we all should be), I think you’ll really enjoy it. Highlights include:

  • The autoimmunity research Dr. Vojdani and his father are tackling and their latest findings
  • The three subtypes of leaky gut and how to treat them
  • Why antibody testing is the gold standard for understanding leaky gut
  • The best tools for reversing leaky gut
  • The strategies and products Dr. Vojdani uses in clinical care to address autoimmune conditions
  • Dr. Vojdani’s thoughts of precision public health and the future of healthcare
  • And so much more!

Resources mentioned in this podcast:

James Maskell: Hello and welcome to the podcast. This week, we feature Dr. Elroy Vojdani, who is a clinician, a physician, and the son of Dr. Aristo Vojdani, who is the godfather of modern autoimmunity.

Today, we talked about some really interesting clinical information. We talked about the three different sort of subtypes that makes up what we now call leaky gut. We talked about antibody testing and why it’s the gold standard for understanding leaky gut. And then we also just talked about some of the tools to reverse leaky gut. And we talked about some of the strategies and products that Dr. Vojdani uses in clinical care. It was a really interesting half an hour. I think anyone interested in the future of autoimmune disease reversal, this’ll be a very interesting half an hour. Enjoy.

So a warm welcome to the podcast, Dr. Elroy Vojdani. Welcome, Doc.

Elroy Vojdani: Thank you for having me. I’m happy to be here.

James Maskell: So it’s been such a regular, consistent conversation throughout the evolution of medicine about this new era of autoimmunity, and ultimately some of the new science. And ultimately it’s an area where functional medicine is proving to be a lot better operating system for taking care of autoimmune disease. And I guess the first question I wanted to know is what’s it like coming up to be a physician when your father is basically like the godfather of predictive autoimmunity?

Elroy Vojdani: It was definitely a different childhood, but an amazing one. I think the conversations about what in the environment are triggering poor health overall in the United States were regular for me from like 12 years old on. So 25 years ago, that wasn’t very commonplace in the world and I definitely noticed that. But now, at the other end of it, I’m like, “Wow. My dad was such a tremendous wealth of knowledge and so ahead of his time.” I’m lucky to have had that as a part of my life when I was growing up.

James Maskell: Yeah, it’s an amazing, sort of unique viewpoint into really, I think, the future. So for those who you who are listening, I’m sure most of them are familiar with your father’s work, but maybe you could just give sort of an overview on what you guys have been working on together since you came into clinical practice and on research because I know there’s quite a range.

Elroy Vojdani: Yeah. So my dad’s world and specialty is really the impact on the environment and the total word of the environment on the immune system and in particular how things in the environment specifically may trigger or contribute to autoimmune disease. And for that he’s known as the father, or godfather, of functional immunology.

My work with him in the last four to five years has really been focused on two areas. I’d say the intestinal health, specifically trying to identify markers that reliably and reproducibly indicate some abnormal function of normal physiology of the gut. And we focus mostly on intestinal permeability there.

And then we’ve expanded from that into trying to investigate the gut-brain axis and trying to develop blood testing to give a clinician or practitioner an accurate assessment of what might be happening with that axis and where the impact to the brain might be specifically happening.

That began with research in the world of Alzheimer’s disease actually. So that’s really where we are now. We’re in the space of the gut-brain axis and trying to quantify abnormalities in that area.

James Maskell: So today, what would you say is the most sort of like…you’re practicing, I mean, you’re in clinical practice day to day anyway, right? You’re seeing patients?

Elroy Vojdani: I see patients every day.

James Maskell: Okay. So when we’ve talked about this gut permeability, I mean ultimately I’ve talked about this as sort of like the most important clinical leverage point for maximizing health span and minimizing health costs, which is, you know, what we’ve been talking about all the way along. So what do you see as sort of the best practices today for predictive autoimmunity?

Elroy Vojdani: I think absolutely when you get a patient in your office that has a known diagnosed autoimmune disease, intestinal permeability is the most powerful piece of information that you can gather on that patient, because it represents the most powerful venue that you can cause some desired immune modulation. And it’s, to me, such…we have the ability to specifically quantify this process for our patients. And the area that I see overlooked here is oftentimes a patient will come into a clinician’s office and the clinician will say, “I know you have leaky gut.” Right?

And that comes from how often we have success with specific diets with autoimmune disease and also with, I think, the frequency that the literature supports a patient having leaky gut. But the part that’s missed there is when that patient first walks into your office, there are several different types of intestinal permeability that are present, potentially present. The quantification of their severity is also tremendously important. And getting a relatively cheap, reliable, objective data point for them at the beginning that you can then monitor for them objectively three or six or seven, eight months down the road, to me is one of the more impactful things that you can do with those patients, because you know that you’re having impact on their autoimmunity from a cellular signaling perspective.

But the old adage of gut first with autoimmune disease is absolutely tremendously important. And then the other thing that I find, another big game changer is when you get a patient in who has the signs and symptoms of potentially auto-inflammatory, or maybe brewing autoimmune disease that hasn’t been diagnosed yet, that’s your window of opportunity for them to try to pick up what specific autoimmune diseases are brewing for them and to do something about it for them at that point.

James Maskell: And through all of your research, what have you come to know about how this sort of, the gut barrier works that maybe most clinicians wouldn’t know about just because they’re not so deep into it?

Elroy Vojdani: I think that understanding that leaky gut as a total process is actually several unique abnormal processes happening that can combine to be one big clinical picture. So what I mean by that is when we talk about leaky gut, people typically think of the abnormal processes with zonulin, the increase in paracellular permeability. And there are several other types that go beyond that. You can have transcellular permeability from actual physical damage to the epithelial cell. And then there’s another type called chronic endotoxemia where you get migration of lipopolysaccharide from anaerobic bacteria from inside the gut into the bloodstream. And though we really only traditionally call that zonulin paracellular permeability leaky gut, really all three of them are leaky gut and they’re all individually important in their own ways. Each one of them will point to a different process.

James Maskell: And so what’s the best way to sort of differentiate and learn exactly what’s happening in the gut of the person sitting across from you?

Elroy Vojdani: So blood testing to me, serum testing for antibodies to the specific targets of each type of these permeabilities is the most accurate way to do this. And this is an area that my dad and I have published about extensively. But to look for paracellular permeability via the zonulin pathway, we look for antibodies to zonulin. That’s because zonulin is a very large macromolecule. Its half-life is very short on the order of a few minutes to an hour or so. Antibodies to zonulin, because the immune system is not used to recognizing this protein, are therefore produced during permeability, and they’re stable over the course of several weeks. We did a head-to-head study of zonulin levels versus permeability that was published in the World Journal of Gastroenterology in 2017 showing that significant difference and showing that antibodies were superior.

So that for the paracellular pathway. For chronic endotoxemia, again we’re looking at antibodies to lipopolysaccharide. LPS has a half-life of four to six minutes, which has been well-established. So again, we need to look at antibodies to reliably detect this abnormal process. And then for transcellular permeability you can look for antibodies to actomyosin, which are a smooth muscle component of the epithelial cell themselves.

James Maskell: Wonderful. So, you’re getting that kind of clarity, you mentioned you’re now starting to understand the gut-brain connection. How does the defects in those structures affect, you know, sort of make their way out into the rest of the body?

Elroy Vojdani: Great question. So, we think of leaky gut as the window to abnormalities with the gut-brain axis. And that’s absolutely true, right? And so that can happen really in two ways. First would be through leaky gut you develop antibodies to foods that you’re consuming that cross-react with neurological tissue. A very good example of that is casein cross-reacting with myelin basic protein. So you have an inflammatory reaction that’s beginning at the gut. You create a food reaction because of it. That food reaction has the unintended consequence of reacting with your neurologic tissue.

And then the other way the leaky gut results in disruption of the gut brain axis is through the penetration of bacterial toxins into the bloodstream, and therefore to the rest of the neurologic tissue. And the two major toxins that we know about that do this right now are LPS, which I mentioned previously, and now we’re finding that another toxin called bactericidal lethal distending toxin has a tremendous role in the initiation of neurodegenerative disease as well.

There are now rat studies that exist where you can deposit that bacterial toxin in the gut, it’ll then migrate up the vagus nerve, it’ll start the deposition of an abnormal protein called alpha-synuclein and that rat will get their version of Parkinson’s. If you snip the vagus nerve in that situation, the rat will not get Parkinson’s. So the models for this bearing true are really starting to solidify in the animal research world.

James Maskell: Yeah, that’s super interesting. So obviously leaky gut is a concept that 20 years ago was considered quackery and is now considered cutting-edge science. But obviously there’s a range to which practitioners who understand this concept actually doing it right when solving it. So what are some things that you’ve learned from your work that you see maybe being sort of misunderstood or mis-practiced by sort of like practitioners who may be just getting into working and understanding leaky gut and working with it that you would like to help them to understand.

Elroy Vojdani: So again that first point of assuming your patient has leaky gut when they walk in and just treating them for it, I think, is a mistake. Knowing, you know getting that objective quantification of what type and how bad it is, and then giving yourself a tracking tool going forward is really, really important. Some patients respond in three months, some of them take six months, some of them take 12 months and you’re never really going to be sure that you’ve healed the underlying interface abnormality unless you have that tool in front of you.

Another big mistake that I think a lot of people make is they order the testing in the inappropriate way. So every laboratory company under the sun that practices in functional medicine will offer their form of leaky gut testing, right? And you need to really be very careful about being sure that that form of testing has been validated and is clinically meaningful.

So for example, stool zonulin levels have been offered. There really is no clinical evidence to support that that’s the appropriate use of zonulin, and then also blood zonulin levels were initially offered. So you really have to understand why you’re using the test, which test to use, and then when you use it appropriately to also track going forward to make sure that your desired clinical outcome is happening.

That’s because one leaky gut protocol might work for five out of 10 of your patients. It’s not going to work for all 10 of them. You’re going to have to tweak along the way for the ones that don’t respond the right way. And there are various diets and supplements that I have in my arsenal that I use. I’ll start off with what my hunch tells me is right for that patient and I’ll go forward from there. Essentially, if I need to troubleshoot, I’ll troubleshoot.

James Maskell: Yeah, I’d love to get into some of that arsenal that you spoke about, but just before we get into that, are there some causative factors for this process that you’ve uncovered through either intaking or through labs in this sort of lifestyles of the patients that you’re seeing that have these things in common that sort of go underappreciated in driving the pathology?

Elroy Vojdani: Yeah. The big ones that are talked about in the literature certainly hold true and I think it’s no mystery. You know, born via C-section, lack of breast milk in the first year of life, large antibiotic exposures, exposures to medication like a NSAIDs or proton pump inhibitors. Those definitely all hold true and you’ll find that clinically relevant when you do the testing for this.

The big one that I’m starting to appreciate more and more in my practice is stress. Patients that are just living that chronically stressed rat race lifestyle that don’t have the clear other indicators. They didn’t have a big antibiotic exposure. They were born via vaginal delivery, they were breastfed. They have leaky gut all the time. And they can be the most difficult ones to manage because you’ve got to coach them through emotional coaching habits and coach them through this huge lifestyle change that needs to happen. And it really takes a long time, and it takes a lot of trust between practitioner and patient to make that happen effectively.

James Maskell: All right, so now you’re getting right into my zone because like this whole year has really been about group medical visits, and I’m seeing innovation in functional medicine delivery and kind of bringing people together in groups and teaching people about groups and also really connecting people into groups because it seems like most of these chronic illnesses have sort of a biopsychosocial aspect to them. And I wouldn’t be surprised if lonely people as an example with that level of stress that’s caused from social isolation, it might be a driving factor. What do you think about that?

Elroy Vojdani: I think that’s a huge part of it for sure. You know, loneliness is, I think in our digital age these days, becoming so common and so frequent. It has a tremendous physical impact on us. Everything in the emotional realm I think what we’re finding out in the modern medical side is that you can detect physical disruption from it as well. Like, IBS is the perfect example of this. Thirty years ago, we talked about it being entirely psychosocial, and now we’re focusing on all the physical disturbances in someone with IBS. But I think a balance between the two is really true. This is emotional affecting our physical. So loneliness, I think that there’s a lot of difficulties in creating and establishing meaningful intimate relationships for people these days. And that has to have a huge impact on you physically.

James Maskell: Yeah, I mean imagine, I just think one of the innovations that we’ve seen with some doctors we reported in our group series was like doing lab review in a group because they found that like learning from other people’s labs and on what came up for them was good. And you wouldn’t be able to get into maybe the precise details of what their exact labs mean, but learning about all the things that you’ve shared about like what is zonulin? How is it produced? Like what is gut pain permeability, what is gut permeability? These are things that when taught to a group of people, ultimately makes the…for someone to recover from an autoimmune disease caused by leaky gut, they pretty much have to understand why it’s happening so they can modify behavior in the future. And ultimately I think it’s just exciting to see some practitioners working out ways to do it in a way that is going to make it more affordable, and also to give people in some cases access to other people who are going through the same thing to be able to provide support in that journey.

Elroy Vojdani: I completely agree with you. To me a big part of what I think my task is when I have a patient in front of me is to be their educator. And I’ll tell them this, I say, “My job is to be your advocate, to be your investigator and to be your educator.” And I think the most meaningful part of it is to be the educator. If you can give them the power of understanding what is personally going on with them, why you’re instituting the treatments, I think you not only will be more effective in treating them in the short-term, you’re also empowering that patient to know that they have the ability to impact their life in a positive way going forward. And I think there’s nothing more valuable or powerful that you can give a patient.

And I think the group setting is actually an ideal way to do this. And you and I didn’t talk about this before James, but since seeing a lot of the push that you are a part of for creating group visits, I have plans to start instituting weekly group visits in my clinic. We’re going to be moving into a bigger space in February of next year, and I made sure that there’s going to be a conference room over there so that we have the space to be able to do this because I do believe it is very powerful going forward.

James Maskell: Awesome, that’s so great to hear and I definitely think that gut group visits are crucial. One, because obviously what we’ve talked about before, the efficiency of education, but I’ve heard of a lot of practitioners who do group visits based on patients who have leaky gut because ultimately that can be a range of diagnoses. And ultimately doing group visits based on root causes is an exciting sort of innovation because then people start to learn, “Oh, this guy who has arthritis is actually like a lot more similar to me than I thought even though I’ve got Crohn’s,” or whatever.

Elroy Vojdani: Absolutely. Yeah. I mean because it’s such a common root cause for so many things, it makes sense for everyone to come together and see how this thing could impact them in many different ways.

James Maskell: That’s awesome. We’ll definitely put links to some of your research. I know you’ve shared it at A4M and other areas, but let’s get into some of the weapons that you were talking about earlier about how to really deal with this. So you’ve got the information, you see whatever you’re seeing on the information that’s coming in, what’s the plan, right? How do we get people better, how do we get people better as efficiently, as quickly, as cost-effectively as possible. What are some of your strategies on that end?

Elroy Vojdani: You know, the way I look at it when I see a patient who has either autoimmunity or an inflammatory disorder that identify as having leaky gut is the faster that I can heal them, the better their body will be able to recover and the better their body will be long-term. So I kind of look at it as a race against time. So I tend to be a little bit more aggressive. So the patient will come in, obviously if they’re consuming processed foods and gluten and dairy, the dietary recommendations in that world are pretty straightforward. I’ll do some varying of the autoimmune paleo diet. And if there are specific indications that they’ve got a rheumatologic disease, I’ll throw in complete lectin avoidance on there as well. And that’s based on research that my dad and I just completed and are in the process of publishing with Dr. Datis Kharrazian as well.

After that in the supplement world, you know the basics, glutamine, aloe, licorice, glucosamine, you know these are all things that I routinely use, probiotics, turmeric. But for me, the big game changers have been when I find that chronic endotoxemia component, that can be the most stubborn component to heal and I think the one that impacts patient’s joint health and their neurologic health the most. So I use a product called SBI Protect from Ortho Molecular. If I find that LPS is an issue for them, I will use a short-chain fatty acid product called EnteroVite™ from Apex. And then we’ll also use a liposomal form of glutathione to help with the hepatic detoxification and recovery from that LPS injury as well. So specifically when I find chronic endotoxemia as a component of their leaky gut, I push hard. I want to get that LPS out of their bloodstream as fast as possible. And those three things have been very big game changers for me.

James Maskell: Yeah, that’s awesome. What are your thoughts about like sort of removing the insults? What are some of the typical insults that you’re removing that maybe you don’t see other people remove or do you have consistent dietary protocol for people who come in to see you?

Elroy Vojdani: I try not to actually. I try very hard to try to gauge the diet based on the personalized data that I’m getting for them. If I have the luxury to get a food immune reactivity map and they have a known autoimmune disease, I’m very specific about this. So that would be a Cyrex Array 10 for these patients. So basically what I’m doing in that sense is let’s say a patient comes in with Hashimoto’s and they’re TPO antibody dominant. The traditional elimination diet for that is gluten, dairy, corn, soy and eggs, right? Why? Why are we doing that? Right? Is there data to suggest that those dietary proteins are a cause for Hashimoto’s specifically? No, there isn’t.

My dad and I actually also wrapped up a research study trying to map out the cross-reactive epitopes between TPO and what else is out there in the dietary world. And it turns out that wheat, soy and bean agglutinins are the biggest cross-reactants. So in that case I’m putting them on a wheat, soy, and bean eliminated diet and seeing how we do with TPOs. And I’ve found that to be way more successful in implementing, because it’s less of a challenge for the patient. And I’ve found it actually more clinically relevant.

So that’s what essentially I’m trying to do. I don’t give everybody here’s the diet, you have an autoimmune disease. If they will allow me the investment into the information, I will do a food reactivity map. I will personalize it to their autoimmune condition and give them the dietary change based on that.

James Maskell: That’s awesome. Well look, I hope that this podcast informs people in our community about sort of up-leveling the quality of care for predictive immunity across the practitioner channel. I guess one thing I wanted to just ask you about, because obviously you spend a lot of time probably thinking about this too, but if I come at it from like an economist point of view and thinking about okay, how do we maximize health span, how do we minimize cost? And ultimately, it seems to me that leaky gut, and solving people’s leaky gut, and preventing leaky gut, and then predicting leaky gut, is probably given, one, how many diseases it affects, given two, the cost of dealing with those diseases and the cost of Humira and all of the autoimmune biologicals that ultimately this might be the most significant thing that we could do in terms of a public health intervention that’s very personalized. I mean, Dr. Bland has talked about this idea of precision public health. What are your thoughts on that concept?

Elroy Vojdani: I couldn’t agree more with it. You know, autoimmune disease now as a whole, not even including autoinflammatory diseases, if you just said autoimmune diseases as a whole are the most prevalent group of diseases in the U.S. and the largest financial burden to our entire healthcare system. So that we’ve focused a lot on heart disease and cancer and Alzheimer’s, autoimmune disease is our biggest problem financially, and we’re having a tremendous blossom in the amount of people that are experiencing autoimmune disease, which means that we’ve got to be proactive about preventing it or at least risk-reducing it. We live in an era where the data that is available to make that yes or no, you’re at higher risk and this is where it’s coming from in your environment, it’s so readily available it doesn’t make sense to not apply it to everybody and give them the tools they need to either risk reduce or eliminate their potential for autoimmunity.

The problem is the number of clinicians that are trained with the understanding to do this are limited. We can try to train as many people as possible, but with 50 million people plus in the U.S. you’re going to need every physician in the entire country trained on this to be effective in managing it. So I think we need to harness what technology has to offer us and start delivering these data points to patients direct at home in easy and affordable fashion.

So part of this would be empowering them with the knowledge, empowering them with the data and giving them the tools that they need to do something about it at home, without having to go visit a clinician in the office. At least at a basic level, you know? Start giving people that basic information. And then my hope is…I’m at the beginning of creating a product in this realm actually with the help of a colleague of mine. And my hope is that with some data and a few years behind us, we can go to payers and say this results in significant risk reduction. You should incorporate this for all the payers that come into you initially. And it’s a minimal cost and maximal cost prevention on the backend so that we can start talking about this being accessible for everybody in the U.S.

James Maskell: Yeah, absolutely. And so, I can imagine what you’re saying kind of looks a little bit like some of the direct-to-consumer lab companies that are out there. Obviously you can do a lot with kind of like health coaches and so forth, and working with practitioners. But ultimately, you know that, what do you see as the benefit of the sort of direct-to-consumer model as far as scale?

Elroy Vojdani: It’s unlimited, right? I mean that’s the benefit when you’re using human resources like me, or any of the other warrior colleagues of mine out there that are on the practitioner side, you can only train so many of us. I think there’s no way you could train as many of us to even keep up with the growth of autoimmune disease, let alone how many people are currently being impacted. And it’s such a hole in the current construct of Western medicine right now that we’re just not going to fill it unless you use the advantage of technology and unlimited scalability and cost reduce this on scale and just get the information to people so they can at least do the most meaningful basic parts of this while we hopefully start educating the rest of the medical industry to start playing their part as well.

James Maskell: Absolutely. Well look, this has been a great half an hour. I hope that everyone who’s listening has got a lot from it clinically and I’m excited to see that. You know, we may do some more things with Dr. Vojdani in the future because I think this is a super-important conversation. I think that autoimmune disease is the disease category where functional medicine will really, the functional medicine concepts will make it to the masses and just really excited to be able to see that smart, sophisticated people are working on the same problems that we all care about. And that ultimately we’re facing the right direction. So, thank you for your work. Thank you for your time and being here on the Evolution of Medicine podcast. We’ll put all the details in the show notes on where they can find out more about your work, but in the meantime, this has been James Maskell, your host for the Evolution of Medicine podcast. Thanks everyone so much for listening and we’ll see you next time.


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