On this episode, we have Dr. Elroy Vojdani returning to the podcast. A few months ago, he came onto the podcast and did our most popular show of the year, talking about the role of food and autoimmunity and how it relates to COVID-19. On this episode, he discusses the role of mitochondrial dysfunction in immunological decline. This is a great episode with a lot of information on the immune system and how to make it more resilient.

Highlights include:

  • The role of the mitochondria in a well-functioning immune system
  • How functional, whole-body medicine can be helpful for long COVID
  • What nutrients and supplements can help build a resilient immune system
  • And so much more!


Mitochondria and Immunity: The Critical Connection


James Maskell: Welcome to the Evolution of Medicine podcast, the place health professionals come to hear from innovators and agitators leading the charge. We cover the latest clinical breakthroughs in health technology, as well as practical tools to help you transform your practice and the health of your community. This podcast is brought to you by the Lifestyle Matrix Resource Center, who provide a range of options to help you deliver successful, effective, functional, and integrative medicine. To find out more and to get started, go to goevomed.com/lmrc. That’s goevomed.com/lmrc.

Hello and welcome to the podcast. This week we have on the show, Dr. Elroy Vojdani returning. A few months ago, he came onto the podcast and did our most popular show of the year talking about the role of food and autoimmunity and how it relates to COVID-19. Since then, I had an opportunity to connect with Elroy at the PLMI Conference, and he told me about an upcoming talk that he was going to be giving at A4M called, “The Role of Mitochondrial Dysfunction in Immunological Decline.” And really the conversation that we had helped me to understand all the things that have gone on with COVID, right? The fact that elderly people get it worse, the fact that people with comorbidities get it worse. Is there some unifying framework by which we could understand this and then in our practices help people? And there is, and it all revolves around the mitochondria.

And so we’ve got a special podcast here today. We’re going to get into the role of the mitochondria, how they’re connected to the immune system, to immunosenescence. It’s a really, really fabulous interview. I think any practitioner anywhere in the world or anyone who’s just interested in COVID and what’s going on and how we can build more resilient systems will be super into this conversation.

Thanks so much for the sponsorship of this podcast. We have the Lifestyle Matrix Resource Center who have a Group Visit Toolkit that is all around immune regulation. That would be super relevant to this. Also, Fullscript. If you go to goevomed.com/fullscript, you can get yourself your own account and you can order all the supplements and the nutrients that are mentioned by Elroy here. And we’re super excited about our partnership with Fullscript. And also if you are looking for a community of like-minded practitioners, go to functionalforum.com. You can see the meetups that are growing there, the communities that are growing all around the world. We got new communities launching this month in Nashville and San Diego. And so we’re super excited about all the communities that are building too to support this movement. It’s an amazing half an hour. You’ll really enjoy. Dr. Elroy Vojdani, take it away. So a warm welcome back to the podcast, Dr. Elroy Vojdani. Doc, welcome back.

Elroy Vojdani: Good to be here, James. Good to see you again.

James Maskell: So our most popular podcast of the year was the one that we recorded on autoimmunity and food. Obviously it’s the hottest topic in the world or as it relates to COVID. It’s pretty hot. And then I wanted to jump into a conversation that we had when I was at PLMI Conference and we were chatting. And I guess just to get into understanding sort of how the immune system breaks down over time, what could explain why America’s healthcare outcomes are suboptimal to many other places that seem to have “worse healthcare.” So let’s just jump into that. You mentioned a phrase that I think most practitioners would probably know, but let’s just start there. What is immunosenescence and why is it important to understand?

Elroy Vojdani: And so immunosenescence essentially just means quiet immune system. So this is a hypofunctioning dysregulated immune system, and it can happen in a few different ways. You could have deficiency of the humoral immune system. So that would be low antibody production and/or deficiency in the adaptive immune system. So that’s a typically low imbalanced T cell or B cell function.

James Maskell: Okay. And then what’s the driver of it?

Elroy Vojdani: Yeah. First of all, COVID has been a very, very big propagator into the look at immunosenescence because what we’ve clearly seen from the experience perspective over the last year and a half, almost two years now, is that those that suffer from immunosenescence, essentially those that are elderly, have chronic and inflammatory disorders, are on immunosuppressants. They are much more likely to suffer from the long-term consequences or mortality morbidity of COVID. So this has come to light because it looks to be so clinically important. People suffer dramatically from this viral infection or other things when they have signs of immunosenescence. And the number one cause of immunosenescence is a term called or a process called inflammaging, essentially, that is chronic long-term inflammatory processes that go unchecked or undetected. And as we know, obesity, hypertension, intestinal inflammation, these are all very big causes, sources of inflammaging. So many people suffer from this without really knowing it. So basically inflammaging leads to immunosenescence and it’s a very important area to look at and to treat.

James Maskell: Awesome. Yeah. So when you look at the list of the types of people that have a bad outcome with COVID and you see age is the number-one determinant. And then further down, you’ve got comorbidities. Is that all under that same umbrella?

Elroy Vojdani: Yeah. It real breaks down to how much of a weakened immune system is there and what specific subtypes of immune weakness are present. So there are certain types of T cells called CD8, also known as T cells suppressors suppressor cells that are extremely important when it comes to COVID response. And whether you’re elderly, have a chronic inflammatory disorder, are obese, whatever metabolic arrangements are present, it’s pretty universal that that’s a specific type of immunosenescence that’s present for those people. And I guess it just happens to be that many different things end up with that particular type of immune suppression and are therefore significantly at risk for COVID giving them some big problems.

James Maskell: Yeah. Well, I guess that’s where I really wanted to dive in because when we spent some time together at PLMI, what I kind of gathered from the conversation that you and Jeff Bland were having at dinner was just the role of mitochondria in this. I’m not a clinician, but I mentally compartmentalized mitochondria as something to do with metabolic function and energy. But ultimately hadn’t really, I guess, predicted, I guess that that mitochondria would play such a significant role in this whole process. And that’s kind of what I got from the conversation. So can you sort of take us into the science of that, the role of mitochondria and then how the mitochondria is playing a role in your immune function?

Elroy Vojdani: Yeah. I’m happy to. So that conversation really started as we were talking about, I think, the way we think about our interactions with other organisms really progressing as time goes on. Dr. Bland is obviously very much at the forefront when it comes to understanding interactions with the microbiome and the symbiosis that really occurs there. And another area where we have very interesting and essential symbiosis is with mitochondria, things that began as external individual organisms that have now become an integral symbiotic part of that. These are organelles or think that have their own DNA, have their own independent function. It just happens to be that our life depends on them and their life depends on us. That’s the way that we have evolved now to have this relationship with them.

So I think it’s probably an area in the world of chronic health that we don’t understand a great deal about. What we have started to see is that there is an overlap between people who have mitochondrial dysfunction and an overlap between people who have immunological dysfunction. And I think as a scientist and clinician, the logical question to ask is, how are those two things interconnected with each other? And as you dig into the literature, you’ll actually see that they are one to one. They are very, very intimately connected. And the mechanisms in which mitochondrial health immunological health are starting to come to light. And the thing that I’ll be speaking at this year’s annual A4M conference about is understanding that one-to-one relationship. So if you’re going to treat someone’s immune dysfunction, you also have to treat their mitochondrial dysfunction as well.

James Maskell: That’s super, super interesting. So can you just give us an overview of the role of the mitochondria in immune function? What’s it doing?

Elroy Vojdani: Yeah. Again, we don’t understand a humongous amount about this. What we do see now that we have the technology to start looking at different free strands of DNA and damaged protein particle rolling around that you’ll commonly find damaged mitochondrial DNA in patients who suffer from inflammaging or chronic inflammatory processes. And those patients will also have markers of immunosenescence as well. And there looks to be very significant interplay in the mechanisms in which a damaged mitochondria will signal to the immune system inappropriately to drive down production. And the mitochondria themselves also seem to have an important role in when they’re healthy building normal immune cells.

But quite honestly, there’s a lot of gray area in that space in between. It’s really more correlative. And then there have also been studies that look at when you enhance mitochondrial function for somebody who has immunosenescence that their immune system will also rebound on the other end of it. So, I think the best that we can solidly say is that the overarching process of chronic inflammation likely leads to long-term damage of both of them and how that specifically happens is still a little bit unclear.

James Maskell: Yeah. I was listening to Dr. Hyman did a podcast with Leo Galland and talking about long COVID and potentially functional medicine interactions and functional medicine protocols for long COVID. And part of it was showing that if you take this sort of whole-body approach that is successful for reducing whole body inflammation that, that would be successful. I guess that’s following the same train of thought, right?

Elroy Vojdani: Yeah, absolutely. And I think that, again, this is just meant to expand that idea of what is whole body medicine, right? I think a lot of us talk about treating the source of the inflammation, maybe even have protocols for immune enhancement and detecting the different type types of immune dysfunction may be present. This is really meant to also bring to the front of thought process that specific mitochondrial enhancement protocols are necessary if you’re going to treat that person at the same time. In my opinion, long COVID is a perfect example of a disease process where you see simultaneous mitochondrial damage and also very clear immunological damage and dysfunction as well to happening at the same time. So they both have to be addressed.

James Maskell: Well, so how prevalent is mitochondrial dysfunction in the population?

Elroy Vojdani: As prevalent as chronic inflammatory diseases are and immunosenescences. I mean, we’re I think starting towards the majority of us in the United States and the Western world suffering from these, and that’s only growing, unfortunately.

James Maskell: So what were specific conditions, for the clinicians who are listening, what are things that people would come in with where you’d be like, okay, let’s look into mitochondrial dysfunction as a driver?

Elroy Vojdani: Yeah. I say to me in my practice, the two big areas that we see it are a specific subtype of intestinal dysfunction called endotoxemia. This is the passage of a toxin from gram negative bacteria from the inside of the gut into the bloodstream on a somewhat regular basis. Lipopolysaccharide is the endotoxin that causes a very dramatic immunological response. People who suffer from this happening unknown for years will end up with a chronic fatigue, chronically dysfunctional immune system picture along with the intestinal issues that they experience along the way. And as I’ve gone on in my years, I’ve learned how important mitochondrial rejuvenation protocols are to getting that person back on their feet. I think obviously when everybody thinks about fatigue, it comes to mind, but anything that’s very powerfully or potently and inflammatory is going to necessitate that mitochondrial treatment component.

The other thing that I think oftentimes has a big mitochondrial impact is chronic mold exposure. The interesting thing is that those two things, endotoxemia and chronic mold exposure, have very different immune system pictures, both dysfunctional, but dysfunctional in very different ways. So two areas where mitochondrial dysfunction is present and immunological dysfunction are present, but they look completely different.

James Maskell: Okay. So you mentioned mold there. What are other ways by which mitochondrial function starts to go downhill? What are some of the drivers of it in our modern lifestyle?

Elroy Vojdani: Yeah. We have to I think kind of acknowledge that also aging has a big role in decline in mitochondrial function, and there are certainly ways that you can limit or impact that hit to the mitochondria. But, in our modern world, that type a go-go-go from when you’re young until you’re old is going to impact mitochondria more than they normally, I think, maybe designed to be impacted. And obviously chemicals, pesticides, a lot of things that we’re all unfortunately exposed to on a regular basis have been shown to be very potent damaging elements to mitochondria as well. So it’s kind of everything that we’re surrounded with as human beings these days unfortunately unless we live in the remote wilderness, which is getting more and more appealing.

James Maskell: Yeah. I moved to the remote wellness about three months ago. Well, not that remote, but enough to be above the big smear on the…If you look at the map of glyphosate, there’s a big smear across the center of California, which is obviously where all the agriculture’s happening. So just living a little bit above that up in the mountains I feel like is sort of trying to make a way out of that. I guess last year when I went to a conference, I heard Bob Naviaux speak for the first time. And it seemed to me that this cell danger response was really central and with regard to mitochondria. And that was super fascinating. Do you want to just talk to that a little bit because that’s really the autism sort of connection as well, right?

Elroy Vojdani: Yeah. I think it’s probably a huge part of mitochondrial dysfunction for sure. Our understanding of where cell danger responses can be helpful, where chronic cell danger responses can be very harmful is again another area that’s very much an evolution, and we probably will know a lot more about that in five or 10 years. But clearly how the mitochondria themselves get triggered by an external influencer chemical exposure and their reaction to it has a, I think, a very big part to play in this maybe bigger picture of things we call inflammation, but are more likely mitochondrial dysfunction triggering cell danger responses.

James Maskell: Yeah. Interesting. All right. So for those practitioners who are seeing these kind of patients, what’s the testing or what assessment I guess that you do to determine the health of the mitochondria? I guess initially what are things that you’re looking for in a intake and then what are some other tests that you could order that would give you a better understanding of what’s happening in that level?

Elroy Vojdani: To be totally honest with you, I hope that this is an area that we get a lot better at. I think that our current testing and maybe even our current questionnaires to look at whether mitochondria are impaired or are limited to say the least. I mean, part of that is because we’re trying to probe an organelle that lives inside the cytoplasm of our cells. So we’re looking at a cell within the cell. So that’s on its own going to be very challenging area to accurately get some assessment of what the function of that cell is looking like. So, I’d say from a testing perspective, there are some things available like Mitoswab. Probably nowhere near as good as we need them to be on a clinical basis. So we’re really left with a detailed history and a real detailed discussion with our patients. And part of the hard part is when you’re doing this whole-body systems approach, how much of someone’s fatigue is mitochondrial driven? How much of it is adrenal driven? How much of it is thyroid driven?

And so the way I approach it is you’ve got to look. You got to look at how much is adrenal, how much is thyroid related? What’s the function looking there. And then the very clear, big environmental exposures that are on the most wanted lists for having mitochondrial toxicity associated with them. So mold, pesticides, chemicals, metals. If that’s a big part of their history, I think you just go ahead and presume that mitochondrial dysfunction is there, too.

And again, now that we know that specific immune suppression goes hand in hand with mitochondrial dysfunction, you also have to the really probe the immune system in depth. And that’s something that we do absolutely have the tech to do very well these days. So at the very least getting very good lymphocyte subsets on your patients, looking at CD4 counts, looking at CD8 counts, looking at CD3, CD19, looking at the ratios between CD4 and CD8. And of course also understanding that when you see a CD4 level in a 20 year old versus a 50 year old, those should be different because of aging. So you got to take that into account. And the number of times you’ll find a 30-something year old with a very low CD4 and CD8 count will blow your mind I think when you look if you haven’t been looking before. So, yeah.

James Maskell: That’s interesting. Is that just the modern lifestyle to the next level? Or is that some sort of transgenerational epigenetics. Do you think?

Elroy Vojdani: Probably both. I think a lot of it is our current lifestyle. Obviously, there’s a big movement in the direction of trying into account for these things and pushing back against what our modern lifestyle is doing to us. We’re certainly better, maybe not overall, but many portions of us are better today than we were 20 years ago in understanding and trying to push back against this. But some of it has to be the “inherited physical trauma” from generations before us, the epigenetics. So…

James Maskell: You used a word when we went for dinner that I wasn’t familiar with. And I wanted to just get into before we get into what to do about it, because it seems like I know that there are some empowering messages as far as what we can do with nutrients and lifestyle and in the functional medicine lens, right? But what is mitophagy?

Elroy Vojdani: Just like autophagy is the clearance of dead and dying cells, it’s essentially the same with mitochondria, essentially trying to rejuvenate clear dead and dying dysfunctional mitochondrial cells and bring back normal function. This goes hand in hand with the idea of how do you build back against immunosenescence. Essentially we kind of think of this as there are clones of these cells coming out of the bone marrow, and we want to rejuvenate the stem cells to be able to bring back the clones to life, which is kind of at the essence of pure autophagy the way we think about it these days. But mitophagy is restoring function within the cells that already exist, bringing back healthy, normal functioning mitochondria that are at their full capacity.

James Maskell: And in your clinic, is that happening? Can you see a case and you can say, “Look, when you came in, it was like this, and we’ve done this program. And now you see not just the impact in your energy, but this is the physiological reason why this health improvement has happened?”

Elroy Vojdani: Yeah. Yeah. I mean, absolutely. You can take somebody from…Again, I think the immune system’s the way you can probably more directly observe this at this point. But people come in with low white blood cell counts, low CD4, low CD8, low T reg cells, very low. And then you can build them back to, Let’s say if you’re watching them with three month intervals, build them back to absolutely robust full-blown levels. And this can happen maybe not in an 80 year old, but certainly people well into their 60s, 50s. It’s pretty profound. And then you’ll see their MSQ questionnaire results or whatever you’re using to track their fatigue. You’ll see their markers starting to improve along the way as well. And typically it’s their resiliency to physical challenges that really starts to rebound along the way there that they can push it every once in a while and not feel like they’ve got to lay on a couch for a week afterwards.

James Maskell: Yeah, that’s cool. So cool. Let’s get into supporting people and how do we support mitochondria with, I guess, initially lifestyle and then nutrients supplements or otherwise. What are your go-to?

Elroy Vojdani: It’s not going to be anything revolutionary I think. We have a pretty good toolkit when it comes to all the different elements we use for mitochondrial rejuvenation. So, I mean, there’s the traditional mitochondrial support products, alpha-lipoic acid, green tea extract, all different amino acids there, acetyl, L-carnitine. There’s a lot of basics there I think. CoQ10, obviously. They all work to me. That’s all foundational stuff. So we’ll give patients those full spectrum mitochondrial support supplements at the beginning of the work to try to set the tone for the mitochondria to be as healthy.

And then in my practice when I test and see that the environmental exposures look to be on their way out, I tell patients that this is the time for us to go full-court press when it comes to mitochondria. So we throw very big levels of CoQ10 at them. PQQ, nicotinamide riboside or other analogs. And I think some of the carbon-based molecules, like humic and folic acid that are starting to become regular parts of our protocols these days as well too. Seem to be very mitochondrial enhancing. So yeah, you start out with the basics and I think when you have a good sense of taking care of the root, you move on to everything you have. And diet’s a big part of that too.

James Maskell: Yeah. Where do you look for in the diet for that kind of flexibility and mitochondrial health? What are the key dietary pieces of that?

Elroy Vojdani: So I’m always cautious to comment about diet because everybody has a big opinion out there. What I have found that works the best for me in practice is going plant-rich, maybe not vegan, but very plant-rich and really hitting on phytonutrients. So, lots of blueberries, lots of sprouts. I’m a very big fan of sprout usage. So broccoli sprouts, cilantro sprouts, alfalfa sprouts, pomegranates, things that are very, very high in phytonutrients and minimizing obviously inflammatory intake at the time. So to me, that’s eating the rainbow plant-rich diet. People have different terms for those style of eating plants. But to me that’s a mitochondrial support. There’s some people who are advocates of implementing low carb ketogenic diets in these contexts as well because you’re basically bypassing traditional Krebs cycle in them using different sources of energy. But I have found that to be a little bit too stressful. So we kind of go to the plant-based, phytonutrient-rich worlds.

James Maskell: And also, I guess, not eating, right? Fasting playing a role?

Elroy Vojdani: Yeah. When they’re in the repair phase, huge, right? Because you can, again, really help to signal autophagy and mitophagy, but to me, the very important point there is somebody has to be out of that big inflammatory exposure. You don’t want to, to me, conceptually don’t want to have somebody still battling some ongoing inflammatory process and then throw in what would otherwise be a helpful danger signal suddenly become a difficult danger signal or stress signal for the body to handle. So as long as you’re in the rebuild phase, absolutely. Intermittent fasting, time-restricted feeding, fasting mimicking diets, actually just fasting for 24, 48, 72 hours periodically, all of them can absolutely be healthy. And, James, probably the thing that the literature is most supportive of for both mitochondrial rejuvenation and immune rejuvenation is weightbearing exercise. And it was a very, very well-done study published in Nature two months ago showing the profound effects of weightbearing exercise on immunological stem cell regrowth. So the same is true for mitochondria. Everybody’s different with what they can tolerate, but exercise is probably at the top of the list.

James Maskell: Yeah. Well, actually I knew about that because when COVID hit, they shut down my CrossFit and you were allowed to go and get one piece of weight equipment to take home all the members. So I had this kettle bell and we used to do these family fitness with my wife and my daughter. My daughter couldn’t really manage the kettle bell. But that was because as it all kicked in, I think I asked, I can’t remember, I think it was Mike Mutzel. I was like, “Hey, what’s the one thing that we should be doing this from what you’ve seen in the literature?” And he was like, “You got to get some weights.” So I was super into that and been taking the CrossFit really seriously since then because I recognized how critical that is. And yeah, it’s a good thing for everyone to be doing. So, yeah, thanks for all that insight.

And I think a lot of what you’re talking about is being done in the functional integrative naturopathic clinics around the country. But I also feel that it’s very easy just to get sort of lost in immune health without really thinking about mitochondrial health. And that’s certainly something that has been really interesting to me and why I wanted to have you on the podcast. I guess the last thing that I wanted to just ask you about is, when we spoke last time and this has been part of your work for a while is really looking at this viral molecular mimicry, right? And that was another area where, okay, autoimmune disease patients, how are they going to do with COVID and what’s going on at the sort of the cellular level at that end? And I guess I’m wanted to ask you how that particular, the molecular mimicry side and the mitochondrial things overlap?

Elroy Vojdani: Well, COVID is another great example of that. I mean, we know very well that nucleocapsid in other antibodies that are created following COVID infections cross-react very strongly with mitochondria themselves. And that’s probably a very, very big portion of the long term chronic fatigue that happens to many people following the COVID infection. So mitochondria can take a very direct hit depending on the antigen that’s being circulated in the antibody that’s being produced. COVID along with other viruses being at the top of the list of things in the environment that cause that direct cross reactive molecular mimicry antibody formation against the mitochondria themselves. Another example of an antibody that does that would be EBV or HHV-6. But COVID looks to do it more than anything else we’ve seen in nature.

James Maskell: Awesome. Well, look, thanks so much for coming on the podcast. In years gone by when I used to go to every conference going and meet so many doctors, it was always kind of interesting ideas being thrown at me left, right, and center. I’ve really tried to pare down the number of conferences that I go to. But just in the time that I spent with you and Dr. Bland at dinner and in the car, I just felt like there was enough material in that conversation for so much. And the fact that this conversation is just so hot in our community because ultimately COVID is still here. It’s going to be endemic. The long COVID clinics are busy and picking up. And I really feel like functional medicine could be at the center of solving those things, especially listening to Dr. Hyman’s interview with Leo Galland, which I’d highly recommend.

And also if this is the first time you’ve heard Dr. Vojdani, go and listen to the podcast that we did back in September on food and COVID and autoimmunity because that was really, really interesting too. But yeah, it just feels like this is a really important topic for today and really grateful for you making time to be on the podcast. I know everyone who listens to it really appreciates it. We get tons of great messages from all just about how much they’re learning from the comfort of their own home or wherever they listen to their podcasts. So thanks so much for being part of the Evolution of Medicine podcast again and look forward to continuing our conversations in the new year.

Elroy Vojdani: Likewise. Thanks for having me.

James Maskell: All right. So this has been the Evolution of Medicine podcast. We’ve been talking all about mitochondria and immune system function, immunosenescence. Dr. Elroy Vojdani and this has been the Evolution of Medicine podcast. Thanks so much for tuning in and we’ll see you next time.

Thanks for listening to the evolution of medicine podcast. Please share this with colleagues who need to hear it. Thanks so much to our sponsors, the Lifestyle Matrix Resource Center. This podcast is really possible because of them. Please visit goevomed.com/lmrc to find out more about their clinical tools like the group visit toolkit. That’s goevomed.com/lmrc. Thanks so much for listening and we’ll see you next time.

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