Immune System Support

Mark Hyman, MD

Dr. Mark Hyman is leading a health revolution—one focused on using food as medicine to support longevity, energy, mental clarity, happiness, and so much more. Mark Hyman, MD is a practicing family physician and an internationally recognized leader, speaker, educator, and advocate in the field of Functional Medicine. He is the founder and director of The UltraWellness Center, Founder and Senior Advisor for the Cleveland Clinic Center for Functional Medicine, a fifteen-time New York Times best-selling author, and Board President for Clinical Affairs for The Institute for Functional Medicine. He is the founder and chairman of the Food Fix Campaign, dedicated to transforming our food and agriculture system through policy.

He is a co-founder and the Chief Medical Officer of Function Health. He is the host of one of the leading health podcasts, The Dr. Hyman Show with 150+ million downloads. Dr. Hyman is a regular medical contributor to several television shows and networks, including CBS This Morning, Today, Good Morning America, The View, Fox, and CNN.

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Full Transcript

Automatically generated. Please forgive any typos or errors in the following transcript. It was generated by a third party and has not been subsequently reviewed by our team.

Dr. Mark Hyman
Coming up on this episode of The Doctor Hyman Show. 60% of your immune system is right underneath the lining of your gut. So Yeah. It's there because you're exposed to foreign molecules from food and bugs, and your immune system is the first line of defense. And so when that system gets disrupted, and you get what we call leaky gut, it creates a lot of inflammation.

And so changing your diet has a huge impact on there. Working on your inner garden, your gut microbiome plays a big role. Now, before we jump into today's episode, I'd like to note that while I wish I could help everyone by my personal practice, there's simply not enough time for me to do this at scale. And that's why I've been busy building several passion projects to help you better understand, well, you. If you're looking for data about your biology, check out Function Health for real time lab insights.

And if you're in need of deepening your knowledge around your health journey, well, check out my membership community, Doctor Hyman Plus. Plus. And if you're looking for curated, trusted supplements and health products for your health journey, visit my website, doctorhyman.com, for my website store and a summary of my favorite and thoroughly tested products. What are the things that help us have immune resilience, and what are the things that have changed in our environment or our life or lifestyle that have actually made our immune systems be dysregulated?

Dr. Elroy Vojdani
Yeah. The the most important cell in the immune system is something called a t regulatory cell. And the dominant population of t regulatory cells in an adult lives in the lining of the gut. So the gut is the center of immune resilience. Those regulatory cells are responsible for, you know, kind of balancing all the different sides, making sure that, you know, in an inflammatory attack against something that we should be attacking, we don't end up in that mistake of attacking ourselves.

So the gut is absolutely the center of the immune system and immune resilience.

Dr. Mark Hyman
So the gut the gut is a big problem, and we've messed up our gut. Right? The increasing rates of c sections, lack of breastfeeding, early use of antibiotics, all the gut busting drugs we use, like acid blockers and anti inflammatories and steroids and hormones, and the depletion of, our microbiome by the glyphosate that we're all exposed to. Eighty percent of Americans have glyphosate in their urine, which is a natural antibiotic that kills well, not natural. It's a synthetic antibiotic that kills your microbiome.

And on top of that, you know, we our diets change dramatically. We've reduced our fiber. We've increased ultra processed food. We take emulsifiers that damage our gut lining, cause leaky gut. So we have a whole cascade of things that have happened in our environment, we call the exposome, that have really caused massive damage to our gut, which is where 60% of the immune system is.

And then that's led to, I think, a lot of the rise in chronic illness in general because the guts are not linked to everything from psychiatric disease to cardiac disease to diabetes, metabolic health, cancer, and obviously, autoimmune disease and allergic disorders and asthma, not to mention just the gut issues that people have, like, IBS and all that stuff. So this is a massive problem. It's causing huge amounts of disability and and and disease, and it's not something that traditional medicine does a very good job of thinking about, diagnosing, or treating. And I and I've been involved with, you know, academic centers with these long COVID clinics, and it's kinda embarrassing, honestly, alright, to see how little they know and how little they're doing. And yet there's so much that's known that we can actually do something about.

And I mean, I just, we're just chatting a little earlier about, like, these different lab tests, for example, in Germany that they're looking at that are common in post COVID patients, which are auto antibodies against your autonomic nervous system that affects your ability to regulate your blood pressure and gives you dizziness when you stand up or POTS, you know, possible orthostatic hypertension syndrome. And and we're seeing other other auto antibodies against different tissues, and it's kinda scary. And and, there there's techniques to actually fix it, heal it. We we talked a little bit about plasmapheresis, which they're looking at in Europe, which basically filters out all the bad stuff in your blood and cleans your blood and it's used for a lot of immune diseases. So so talk about, if we had this problem with immune resilience, you know, you know, what what are we seeing with that?

What is what is we're seeing the rise in autoimmune disease, and and and and can you kinda kinda help us connect the dots between the the the decline in our immune resilience, the rise in autoimmunity, and then what's happened with this long COVID phenomenon?

Dr. Elroy Vojdani
Yeah. Absolutely. So, you know, twenty five years of research now kind of starting to look at what is really happening here from a physiologic perspective. Right? You know, intestinal permeability, leaky gut, you know, you've covered that many times on the podcast and in your books.

But, you know, it it's hard to understate how important that process is in chronic inflammatory disease, autoimmune disease, neurodegenerative disease. You know, the more and more and more we look at it, the more we're finding that it is centered to all of these. So that we do keep talking about it. It's rightfully an incredibly important topic of conversation. So, you know, you listed all of the things in the environment that we are consciously or unconsciously exposed to on a regular basis as a population.

Think about it from the immune system's perspective. If if its job is to defend us from threat and we are constantly pouring threat into ourselves, again, knowingly or unknowingly, I think it was only a matter of time until we saw what we are seeing now. You know, massive explosions, viruses that, you know, I think five or six years ago didn't pose such a tremendous threat to Yeah. Us as an adult population. We talked about, you know, RSV.

This last cold and flu season was horrendous. You know, adenoviruses and rhinoviruses, things that typically cause, like, three, four, five days of regular cold causing two or three weeks of pro you know, prolonged congestion, you know, lots of secondary infections. You know, just you're just seeing the immune system just completely failing. So it it's because I think of what we're continuously exposing ourselves to, what that does to the center of the immune system, and then we see all the ramifications of it, you know, now fifteen, twenty, twenty five years down the road, in a population that's dramatically suffering. And, you know, the current medical infrastructure has zero answer for this.

Yeah. You know? It's it's what other biologic medications can we come up with to try to, you know, kind of

Dr. Mark Hyman
Suppress the same.

Dr. Elroy Vojdani
Hinder, suppress. Right? And and now we're getting to the point where, you know, we have patients with three, four, five autoimmune diseases, and and every biologic under the the sun can't control what's going on with them. So it it's a huge problem. It's progressive.

And the only way that we're gonna get out of it is to acknowledge that and to start making conscious choices that limit those continuous exposures to our gut.

Dr. Mark Hyman
Yeah. So so healing the gut is a big part of of healing from autoimmune disease, for sure. That's been, you know, something I've done in my practice in functional medicine for thirty years in the Ultra Wellness Center, and you do that in your practice as a core strategy to help reset people's immune system because it does start in the gut. But there's other phenomena happening. You know, like like, when you look at people who have COVID, they did a a study of over a million and a half people, and it was published in Nature.

Out of the, you know, one and a half million people that they studied in this study that was published in Nature, they found a forty six percent higher chance of getting an autoimmune disease Mhmm. Which is astounding after having COVID. Absolutely. Why why is that happening?

Dr. Elroy Vojdani
That's happening again because I think of the the dramatic loss of immune resilience that we have as a population. So, you know, to, again, to go over those numbers, that was a huge, very well done retrospective analysis, a million and a half people, two different studies combined, showing a very large increase in autoimmunity, and that was in a six to twelve month window after the infection. More and more studies are coming out showing that everything from rheumatoid arthritis, lupus, type one diabetes, you know, virtually every autoimmune disease under the sun can be triggered by COVID. So, again, why is that? It's because our immune systems have lost their fundamental ability to be able to appropriately defend us against viruses in the short term and then also in the long term.

You know? To be able to resilience is an ability to defend yourself and then return to normal, return to balance, to say the threat is gone. Everything is okay. We've handled this. Let's go back to the balance that we're supposed to be in.

And that part is completely gone as well too. People stay in very prolonged chronic inflammatory states. I mean, the average long COVID patient has dramatic symptoms for twelve to twenty four months

Dr. Mark Hyman
More.

Dr. Elroy Vojdani
Or more. You know? And and part of that is because I think, you know, the infrastructure isn't addressing things appropriately, but part of that just speaks to how much from a population perspective immune systems are broken and immune resilience is completely gone.

Dr. Mark Hyman
Yeah. Well, it's so true. And the symptoms for long COVID are just astounding. Like, there's over 200 symptoms described new ones every day. I'm hearing stories from my patients about all sorts of different neurologic issues and gut issues, autoimmune issues, cognitive issues, you know, brain fog, autonomic dysfunction.

And the scary part

Dr. Elroy Vojdani
of it, it I don't know what you've seen recently, but, you know, I think the early batch of long COVID was was predictable. Those who were gonna get really severe or hospitalized forms of COVID, you know, they were gonna have really big struggles afterwards. Now, you know, it's like 45 year old dad walks into the clinic metabolically healthy, not smoking, you know, not a heavy drink. Right? Mild COVID.

Very mild COVID. All of a sudden, horrendous long COVID afterwards. Right? That again speaks to how broken the immune system of the population is.

Dr. Mark Hyman
So is long COVID an autoimmune disease in of itself, or is it just one of the aspects of it?

Dr. Elroy Vojdani
Well, in the in the research that my dad and I have done on long COVID so far, we've sent we found specific autoimmunity in a large percentage of them, but it's certainly not everybody. You know, whether it's, you know, cardiolipin autoimmunity, neurological autoimmunity, you know, a lot of joint related autoimmunity, sometimes thyroid as well. You you that's certainly, I think, one of the signatures, along with something called viral reactivation, which, you know, in the chronic fatigue space, we've known about for a very long time.

Dr. Mark Hyman
Yeah. I mean, that's an important thing when you unpack that because what we're seeing with long COVID is that dormant infections kinda rise up from the dead Mhmm. And tend to get reactivated causing problems. And whether it's Epstein Barr or cytomegalovirus or CMV, it seems to be part of the picture.

Dr. Elroy Vojdani
Absolutely. So there are a large group of viruses that we as adults you know, by the time we're adults, we've been exposed to. We haven't been infected with HHV six, you know, which is roseola, something that we typically get by the time we're three years old, not a big deal. If you are symptomatic, you've got a fever for a couple of days, you have rashes, Epstein Barr virus, the majority of adults are asymptomatic from the infection, same with CMV as well too. These viruses, are are genius in their long term evolution against us.

They they have figured out how to evade complete immune eradication Yeah. By hiding in tissue after the acute infection.

Dr. Mark Hyman
Yeah.

Dr. Elroy Vojdani
But with a normal immune system, they stay in dormancy. They wouldn't dare step out, you know, in into the wild and get eradicated by the immune system. But, what we're finding is that the vaccine

Dr. Mark Hyman
If you have a herpes cold sore

Dr. Elroy Vojdani
Exactly.

Dr. Mark Hyman
It only comes out when you're under stress.

Dr. Elroy Vojdani
Exactly.

Dr. Mark Hyman
It's not there all the time, but the virus is there Correct. Just sleeping. It wakes up when there's some kind of insult.

Dr. Elroy Vojdani
Correct. Right? It's not it's not rolling around in the bloodstream active all day long. But a very, very large percentage of long COVID cases, long COVID patients have viral reactivation as a core of of their clinical symptoms set and and clinical disease. So, again, that that poses the question, what in the world is happening with the immune system in the short and long term following a COVID viral infection?

It's not meeting the demands in the short term and then not balancing itself in the long term as well, which provides a beautiful open window for these reactivated viruses.

Dr. Mark Hyman
And and are there are there good diagnostics immunologically to help map out what's going on with these patients? Because, you know, long COVID is a bucket. Mhmm.

Dr. Leonard Calabrese
But

Dr. Mark Hyman
it's truly probably many, many, many different kinds of problems. And each individual responds to the insult with different manifestations and you may need different kinds of treatments.

Dr. Elroy Vojdani
But let's go over the buckets, if you don't mind.

Dr. Mark Hyman
Yeah. Yeah.

Dr. Elroy Vojdani
Thanks. Currently, with what we understand right now, I break it into five buckets. So there's viral persistence, which is essentially, somebody never fully clears the initial COVID infection. They've they've got this very low level infection that just keeps on going and going and going and going. There's something called super antigen activation, which is parts of COVID have an ability to just dramatically, I I'll just say, piss off the immune system.

There's the mitochondrial dysfunction and loss of autophagy that happens there. There's the microbiome and gut permeability dysfunction, and then there's the autoimmunity component. So if you're going to talk about diagnostics to be able to accurately pick up what's happening with long COVID, you basically have to say, okay. Which one of these five buckets is the person living in? Everyone is gonna have some unique spectrum of those five, though the most will the majority will have, let's say, three or four of them.

So we we don't have diagnostics for the mitochondrial part, you know, maybe on the research side.

Dr. Mark Hyman
There are some things, but they're they're hard to get.

Dr. Elroy Vojdani
They're very hard to get. In Germany and Like the seahorse analysis.

Dr. Mark Hyman
Yeah. I use a IGL lab in Germany that does a detailed mitochondrial assessment. It's a mito swab. It looks at mitochondrial, you know, stuff. But it's organic acids.

But it's it's definitely hard.

Dr. Elroy Vojdani
You and I know that stuff. Right? But not, not every physician out there in The United States. Right? And then Yeah.

Dr. Mark Hyman
These are sort of more functional medicine diagnostics that are not used in traditional medicine, but they're real.

Dr. Elroy Vojdani
They're real, for sure. The viral reactivation stuff, I think, you know, rather straightforward antibodies, IgM, IgG antibodies to different targets of Epstein Barr virus, HHV six, CMV. There's no diagnostics for COVID persistence if that is in case, what's going on. I mean, you can look at, you know, whether there's very high levels of COVID antibody production for long periods of time, and you can infer that there's COVID persistence there. The autoimmune part of it.

You you brought up the lab in Germany that's doing an autoimmune panel, specifically for long COVID, in our studies as well. Neurological targets like myelin basic protein, myelo oligodendrocyte glycoprotein. The blood brain barrier is a very common target that was demonstrated in mouse literature. So you're

Dr. Mark Hyman
basically seeing autoantibodies, basically, your own immune system attacking aspects of your brain and your brain tissue?

Dr. Elroy Vojdani
Your your your the most important defense of your brain, which is the blood brain barrier, you know, disrupted in football players, poxers, Alzheimer's, Parkinson's. So, you know, that that same kind of core defense layer of the brain gets damaged by COVID. You can look at those markers in the blood and then the specific neurological proteins like myelin basic protein, which is traditionally damaged in something like multiple sclerosis.

Dr. Mark Hyman
And and so these these are lab tests that you can do to help sort of sort things out, and tell which type of the sort of five buckets people go in?

Dr. Elroy Vojdani
Yeah. I I it you know, make an attempt to to try to, you know, on on this kind of early leading edge side of things, identify how much of each one of them they're dealing with.

Dr. Mark Hyman
I mean, you've published a lot on this. You published in Nature, which is a major journal and other journals looking at autoimmunity and the exposome and COVID. And I think, you know, it might be helpful for us to sort of, dig into sort of how how do the sort of this persistence of long COVID symptoms, you know, what's the underlying biology that's happening here? Is it is it an overactivation of cytokines? Is it is it autoantibodies?

Is it damage to the gut? Is it, you know, endothelial problem, which is all the blood vessel linings, which affects everything, which is why maybe you have symptoms everywhere because it affects everything. Yep. You know, how does how does it all sort of fit together for

Dr. Leonard Calabrese
people?

Dr. Elroy Vojdani
It's tough because it's it's multiple pieces. But if I was gonna break it down to what I think the core of it is, you know, the the acquired mitochondrial damage and the associated lack of autophagy to me is really core there. So mitochondria are, you know, the the powerhouse of the body. We know that for energy production, but I think it's underappreciated how much a damaged mitochondria will lead to a pro inflammatory dysfunctional immune phenotype, meaning somebody who has a dysfunctional immune system just as the result of the damaged mitochondria. And then from there, there are neurological immune cells called glial cells.

They will enter something called glial, activation and end up with a pro inflammatory immune subset in the brain. So

Dr. Mark Hyman
You can see on fire.

Dr. Elroy Vojdani
Brain on fire. Exactly. So tired, dysfunctional immune system, brain on fire, strictly from the mitochondrial damage that comes from the viral infection. And, you know, of course, in The United States, with all the metabolic dysfunction that exists You

Dr. Mark Hyman
already have mitochondrial issues. Right?

Dr. Elroy Vojdani
Massive mitochondrial issues to begin with. Right? So that's that's why we're seeing a bigger problem with it here, both in the short term and the long term.

Dr. Mark Hyman
So just unpacked a little bit. Mitochondria for everybody, those are those little organelles. There's thousands of them in every cell that take food and oxygen, turn it to energy, and form ATP that our body uses to fuel everything. So when you basically think about that, it it's your engine. And if you run out of gas, you're in trouble.

And so everything doesn't work in the body when you run out of gas. And so what you're saying is the the COVID virus somehow affects the mitochondria in ways that make them less functional and less able to produce energy, and then has this huge downstream effect that even affects the immune system. Absolutely. Because not not a lot of people talk about the connection between the immune system and the mitochondria. What do we know about that?

Dr. Elroy Vojdani
It it it's clear. So if mitochondria can run either on something called oxidative phosphorylation, sorry for the fancy words, but, you know, to to It's

Dr. Mark Hyman
burning carbs.

Dr. Elroy Vojdani
Yeah. Right. Burning oxygen and carbs, but that's a that's an efficient form of, you know, converting food into energy.

Dr. Mark Hyman
It's kinda like a diesel truck.

Dr. Elroy Vojdani
Yeah. Right? Less fuel, more miles.

Dr. Mark Hyman
Yeah.

Dr. Elroy Vojdani
Right? And the more miles you get out of the amount of fuel, the less antioxidants or less oxidative injury is produced by the mitochondria. In metabolic dysfunction like insulin resistance, the mitochondria are not running on diesel. They're running on the least efficient fuel on the planet. So one gallon will get them a mile.

And in doing so, they burn through all of their antioxidant reservoir because the the mitochondrial production relies on this continuous balance between producing things that require us to produce antioxidants to neutralize. Otherwise, the mitochondria damages itself. Right? So you imagine somebody with insulin resistance running on that very inefficient fuel system. They're teetering on the edge, you know, barely making it with the antioxidants.

All of a sudden, a huge oxidative injury like COVID comes along, tipping point. Now the mitochondria cannot, function anymore because you don't have enough antioxidants to meet what it's producing. And, essentially, what happens is it structurally becomes damaged, and it will release its own unique DNA into the cytoplasm which signals to the immune system I'm in trouble. What does the immune system do when you're in trouble? Says, okay.

We've got something we need to fight. Yeah. It puts itself into fighting mode, which is a pro inflammatory mode. The nervous system, the glial cells, know when macrophages, which are a a kind of primal defense cell, are in this white blood cell or in this, like, fight, and they will convert themselves into glial activation and put themselves into this neuro inflammatory fight response, all from the powerhouse of the cell. But that makes perfect sense.

Dr. Mark Hyman
It's a domino effect.

Dr. Elroy Vojdani
Yeah. But it's the most important part of you. Of course, that's gonna happen.

Dr. Mark Hyman
How do we regulate our immune system to do what it's supposed to do and not do what it's not supposed to do, which is happening a lot in our culture. Cause we have such an overactive immune system given our inflammatory diet, given environmental toxins, given the change in our microbiome, given our levels of stress and so on, we all are experiencing, immune system dysfunction at some level. So we also want to understand how inflammation plays a role in aging and how do we regulate the process of getting older without dealing with the consequences of chronic inflammation, which is driving so much of the age related diseases. I wrote about this a lot in my book, Young Forever. There's a whole concept of a chronic systemic sterile inflammation.

It's not inflammation that's coming from getting an infection, but it says low grade chronic inflammation that we now refer to as inflammation. The inflammation that occurs as we age, that actually accelerates every aspect of aging. So how do we regulate that? How do we understand how to not, neglect our immune systems as we get older and make them strong and fit and be able to be resilient and rejuvenate their effect, which is basically diminished as we age, we're less likely to be able to fight infections and cancer. So our immune system is dysfunctional at that level.

And at the same time, it actually is causing more inflammation that leads to more autoimmunity and chronic sterile inflammation that leads to heart disease, cancer, diabetes, and dementia. So we have to really understand the way to, to rethink our immune system, to both upregulate our ability to fight cancer infection, but also reduce the levels of inflammation and autoimmunity that happen as we get older. Now, immuno rejuvenation is a relatively new concept. It was really, sort of framed by my mentor, Jeffrey Bland, Doctor. Jeffrey Bland, the father of functional medicine, who was a student of Linus Pauling and has, has taken this concept of immuno rejuvenation and actually created a whole company around it called big bold health.

And just for full transparency, I'm an investor, I'm an advisor. I believe so much in this, in the work that Jeff's doing. He's taught me most of what I know in medicine. So we had to think about this a little differently. So today we're going to talk about immuno rejuvenation, what it is, how it happens in the body and how to turn it on.

How do we rejuvenate our immune system? Now, why is the concept of immuno rejuvenation better than our conventional approach to immune health? Well, immuno rejuvenation essentially trains your immune system to work better at every level. Your immune systems turn over faster. White cells turn over fast.

You build a new immune system regularly. Everything comes from your blood and bone marrow, right? So your hematopoietic STEM cells are generating new white cells and all the different types of cells. So you really need to kind of learn how to build the right immune system and not have it degrade as we age. Now, what happens as we age typically is not immuno rejuvenation, but a concept called immunosenescence, which is the aging of our immune system.

And that's damage that occurs in our body as a result of a dysfunctional immune system. One that generates more inflammation that causes aging and less immune support that actually helps you fight infection and cancer. And what happens is you, you, we develop these cells called zombie cells. They're terrible cells. I wrote about them in my book.

It's one of the hallmarks of aging. They're also known as senescent cells. And, and what they do is they tend to spread inflammation like a wildfire throughout your body. And they make other cells zombie cells, just like zombies make other people zombies. It's the same idea.

And you end up with a lot of these senescent cells running around your body that are causing you to age faster. So how do we deal with them? How do we actually get rid of them? How do we rejuvenate our body to get rid of the zombie cells to make room for healthy new cells? Well, we are, we're kind of in a, in a, in a challenging moment, in history for human immune systems because we are dealing with things we never had to deal with before.

And and the worst, is our diet, which is a highly inflammatory diet. Our processed food diet, high sugar and starch diet, high refined oils, lack of enough phytochemicals and medicines in food, and anti inflammatory compounds in food and omega three fats in our diet. We are really having a horrible dietary experience in America and around the world globally, and we're seeing that effect on driving all the inflammatory diseases, especially obesity. And then there's not just our inflammatory diet, but all the environmental toxins that we have to deal with. And we're also having, you know, the increased spread of globalization of microbes through, like like, we saw with COVID and the pandemic.

It happens, you know, one in one country a thousand years ago wouldn't get anywhere because you couldn't get anywhere, but now it spreads like a wildfire. So we also have other things like stress, psychological stress, physical stresses, all all create stress on the immune system. So this really sets the stage for this chronic inflammatory state. It makes us more susceptible to in infections, more susceptible to food sensitivities, allergies, and autoimmunity, as well as rapid aging. So the question is how do we lose the science of, immunology, the emerging science of, of, of understanding immuno rejuvenation to help the body to reset, to help the body fight this process of inflammation as we age to help deal with the zombie cells and to basically make our immune systems more resilient.

Well, it's the way basically, you know, we do cleaning up of ourselves is through killing of the bad cells or they die. And then we have to clean and recycle them up. And this is called autophagy. And this is something I've talked a lot about, but autophagy is simply this process of self cleaning, like a self cleaning oven where your, your sort of body has this process to kind of gobble up like with Pac Man, little things called lysosomes, gobble up all the old cells or damaged cells or damaged proteins, digest them and break them down into component parts and then reuse them like recycling. And it is quite a, an amazing process.

And we often have a degraded process of autophagy as we age and there's lots of things we can do to stimulate it. And and a lot of the ways we can do it actually is through food and through the right nutrients and food and through the right phytochemicals and food. So we also have to actually understand how to also rejuvenate our mitochondria because our mitochondria are the energy factories of our cells or the place where we make ATP that drives all of our biological processes. So, when our mitochondria age, we age and we need to rejuvenate our mitochondria as well. So again, this is like my topology is a similar to autophagy.

It's a process of recycling and getting rid of the old mitochondria, getting building new ones. And you need a good immune system to do that because any kind of inflammation will cause mitochondrial dysfunction. So, when when you look at the body's ability to rejuvenate, it's quite remarkable. We have our own built in process of rejuvenation. We have stem cells.

We have immune cells that can help us rejuvenate. We can actually activate all these processes, but we have to learn how. So the question is, what can we do to activate our own body's immuno rejuvenation system? What are the, what are the research showing us about how do we cultivate a healthier immune system? Well, there's a few things.

Food. Right? So food is so important. And so eating an anti inflammatory diet that's plant rich, that's full of phytochemicals, that has medicinal properties in them that actually can kill some of the zombie cells, can rejuvenate your immune system, can reduce the inflammation is so important. So lots of colorful fruits and vegetables.

One of the things that I like, are prebiotics and polyphenols and and they're in various kinds of foods. One of the most important foods for immune rejuvenation is something called Himalayan tartar buckwheat. Now this was an ancient grain, not even a grain, it's actually a flour. So it's not even a grain, even though it's called wheat, it's not wheat. That's confusing.

But anyway, it's grown in the Himalayas and it's got over 132 phytochemicals, many of which are not found anywhere else in nature and have a powerful ability to regulate immunity. And some of them like Corseten, we've seen reverse biological age. And some preliminary data, they've shown that using Himalayan terrier buckwheat, we can actually reverse our biological age by rejuvenating our immune system. So really important. Next is stay active.

So moving your body, exercise, interval training, really powerful for actually rejuvenating your immune system. Over exercising actually can cause a problem, but the right amount of exercise actually helps build immunity. Also make sure you get the right omega three fats because essential fatty acids are so important. And most fish oils are not that great because they process the fish oil in a way that degrades some of the most anti inflammatory components we call proresolvent are mediators, which are basically like breaks on the immune system. And they also take out a lot of the the important things like astaxanthin, which is important for, inflammation.

It is an antioxidant that is found in a lot of the omega three fat containing fish like salmon. So want to make sure you have the right omega threes. Also, you want to fertilize your microbiome. So both polyphenols from colorful plant foods, but prebiotic and probiotic foods are really important. So, and there's, there's a lot of them out there.

We've talked a lot about it on the podcast, but we we want to make sure you're increasing pre and probiotic foods. Also get rid of all the junk, right? The processed food, fried foods, sugary foods, junk foods. These are the things that are just driving inflammation and actually worsening your immune system. Also sleep really important.

If you don't sleep, your immune system is not going to work well. So seven, eight hours of good sleep really important. Now the other thing is that there are positive things that are going to help you improve your immune system, like a stress stressors. For example, we know that that a stress isn't always bad, that there are good stresses that activate your body's own healing response. So basically, this kind of stress is called hormesis, and hormesis is the idea that there's a stress that doesn't kill you that makes you stronger.

So essentially, it takes, some kind of insult, which could be exercise or fasting or a sauna or a cold plunge, and it tricks your body into thinking something bad's happening. And then your body responds by creating a defensive response by activating all its healing and rejuvenation repair systems. So, it's really important, and I think there's a lot of ways to to do this. So, and and these these positive stresses are are important. They help you become more resilient.

So the goal is to become more resilient, more stress, resilient, more immune resilient, be able to adapt to a lot of changes and actually, deal with what has to happen. Now, one of the ways we can actually stimulate the process of healing in the body is through sort of plant compounds that they have used and developed to protect themselves. These are the plants own protective defensive mechanisms, and they're called phytochemicals. And when the plants are stressed, they make more of these. They're their own defense system.

They're their immune system. So it's great to eat these things because they actually activate your body's own healing system. So when plants have to deal with bad soil or temperature extremes or, or, you know, insects that are trying to fight off or floods or droughts. They create all these incredible molecules that are part of their own defense systems. And, and when we actually eat these, it's like eating a little bit of adversity and then they activate our body's own healing systems.

And it's really powerful. Now, Doctor Bland has come up with an approach to immune health that I think is quite brilliant because it deals with three key categories of foods and components in our food that can really rejuvenate our immune system. The first are polyphenols from plants, things like quercetin, luteolin, and, asperidin and all these bioflavonoids that are, that are found in food that can really rejuvenate our immune system. And they, they're, they're found in abundance in this Himalayan powdery buckwheat. The second is eating the right amounts of omega fats, omega three fats, and, and the right kind.

And, and again, I know I'm an investor in big bolt health, but they they've come up with a model of getting fish oil and extracting the omega threes from it and keeping it the proresolvent mediators, preventing the degradation is purified. There's no toxins in it. It's cold process, so it retains all its benefit and it's quite a different omega three fat. The next is, your microbiome. And this is supporting your microbiome through pre and probiotic foods.

And actually Himalayan terrier buckwheat has these amazing microbiome supporting fibers that are quite amazing. And and basically you wanna make sure you get these from all sorts of foods, not just obviously Himalayan, terry, buckwheat, but omega three fats from fish, polyphenols from plants, fibers, and pre and probiotics from, from our food. And they basically help us to build our own immune system. So what are the kinds of other positive stressors other than food that we can use to upgrade our immune systems and immuno rejuvenate ourselves? Well, first is, hormesis.

So hormesis is, is like I said, this idea that what doesn't kill you makes you stronger. And, some of them are pretty simple to do. For example, temperature extremes, hot and cold. So you can do a sauna for thirty minutes at 170 degrees, a regular sauna for thirty minutes, and you can go in and out, cotton cold, hot and cold, that doing that four times a week has enormous benefits for your health and longevity. Cold plunge.

If you get one, great. You can just fill up your bathtub with cold water and get a buck big, horse trough and fill with ice and water and go in that. You can even just take cold shower. That also helps rejuvenate your immune system. Not overeating and actually having a diet that is is time restricted can be very important.

So don't eat three hours before bed. Give yourself at least, you know, sixteen hours, maybe twelve, fourteen if you're, you know, thin and you can't tolerate a longer period. But most people can deal with a sixteen hour overnight fast. That's eating dinner at six and having breakfast at, you know, ten in the morning. So it's not it's not terrible.

And it's powerful to actually drive the activation of autophagy, mitophagy, and killing some of these zombie cells, rejuvenating your immune system. Do stuff that's also challenges you in other ways, whether it's, you know, learning a new sport, whether it's, you know, bike riding or tennis or horseback riding. You know, do something that kinda puts you out of your comfort zone and makes you learn new stuff. I picked up tennis when I was 45 and it was I'm still learning and I'm still improving and growing. So it's it's amazing.

And also, try something crazy like public speaking. I do it. It's it's pretty easy for me, but if you're not used to it, it creates a stress in your system. It may actually be a good stress. So try lots of fun stuff.

Try, do some fun and challenge yourself a little bit, both, in terms of the life activities you can do, in terms of optimizing your diet, in terms of making sure you get all the right nutrients, from polyphenols and from phytochemicals that are great for your gut microbiome, prebiotic fibers, and omega three fats. So that's a great way to really think about reshaping your immune system to actually deal with the ravages of aging and inflammation, but also to boost it so you can actually fight infections and cancer. Sixty percent of your immune system is right underneath the lining of your gut. So Yeah. It's there because you're exposed to foreign molecules from food and bugs, and your immune system is the first line of defense.

And so when that system gets disrupted and you get what we call leaky gut, it creates a lot of inflammation. And so changing your diet has a huge impact on there. Working on your inner garden, your gut microbiome plays a big role.

Dr. Leonard Calabrese
Yeah. You know, I'm glad you brought that up. And and diving into the science just a a little bit, I mean, the the microbiome, which is connected to every organ system in our body, and you've talked about it extensively on this show, is critical in both the development and the function of our immune system. I mean, you know, if you're born with a sterile gut, and you you you you're immune you're immunodeficient, and we know that from animal models, we know it from people. We know a lot about, and you just, you know, I, you've had Doctor.

Hazen on the show, studied this in the most, you know, robust scientific way possible. You know, we know what healthy microbiome kind of looks like, you know, diverse and rich. Mhmm. You know, we've yet to dial it into this organism, that organism. So, you know, we know that good diets that people that eat real food, you know, usually have a more diverse, and rich microbiome, and that supports immunologic health.

Mhmm. I'm reluctant to tell people, you know, Carl Sagan used to say, you know, that extraordinary claims require extraordinary data.

Dr. Elroy Vojdani
Evidence. Right.

Dr. Leonard Calabrese
And so, you know, we we don't know how to reduce it to that crystallized eat this, do this one thing. It's probably much more complicated than that, but we do know that prudent diets versus sad diets have a huge effect on the immune system. And in

Dr. Mark Hyman
the framework of functional medicine, we often people on elimination diets, which is eliminating inflammatory foods and anti inflammatory diet. Things like gluten and dairy can be an issue. Processed food, obviously, eating more whole foods, plant rich foods is really key. So that's sort of what you're

Dr. Leonard Calabrese
saying. Absolutely.

Dr. Mark Hyman
Yeah. Yeah. Alright. So next topic would be, you said exercise.

Dr. Leonard Calabrese
Exercise. So I've been interested in exercise and immunity for decades, actually. It's probably one of the first areas of behavior and immunity that I became interested in. And, it's a complex area to talk. So over the past many years, I try to invite world leaders in all of these areas to my center to visit.

Last year, we had David Nieman, who's one of the, undisputed leaders in this field. And, you know, I do believe in what we call the j curve of exercise, that, people who are sedentary, people who are sedentary are immunocompromised. And we know this, both from the laboratory and the risks of, you know, the kind of the canary in the coal mine that we measure usually is, respiratory illnesses, and how many is normal and how many do you get.

Dr. Mark Hyman
Now being a couch potato is bad for your immune system.

Dr. Leonard Calabrese
It is definitely bad for your immune system as well as virtually every other system in your body, but I'm looking from the lens of immunologic strength.

Dr. Mark Hyman
And we just talked about heart disease and things like that, but this is a

Dr. Leonard Calabrese
whole new view. Doctor. Yes. This is it. The thing that you can do to demonstrate immunologic enhancement is moderate exercise, and you know, moderate exercise is still a moving target.

And, you know, if we look at the guidelines which have been recently revamped, only in the past couple of months, you know, walking is an incredible form of immunologic strength building. And, we, actively endorse in what we talk to about our patients is, just like with the diet, tell me where you're at in this spectrum of exercise. Are you the couch potato and you work in a cubicle, and you're sitting there all day long, you're doing nothing? Or are you, you know, training for ultra marathons at the other end? No matter where you are, we try to move people down a bit at a time.

And, Betsy and I, my nurse practitioner, world's best nurse practitioner, we talk to our patients about instant recess. That's what we call them. We say, you know, if you're totally sedentary, just get up and start moving. And now, I'm copying you, so in my immunologic summits for the past two years, I invite our head yoga teacher from the Cleveland Clinic, Judy, who comes, and we do yoga at all the sessions. So it's the first time I did this at a scientific meeting.

These guys are like, what? What's going on here? Doctor. Doctor. Kempfrey.

Doctor. Kempfrey. And now, it's like so popular. So anyway, we start moving, the needle down to moderate exercise. There still is some data and there's some controversy that's recently been added into this.

You know, the middle path is very strong for health and wellness, right? And, you know, you can too much of something is often as bad as not doing it. Yeah. And there have been a lot of epidemiologic evidence that show people who are ultra exercisers

Dr. Mark Hyman
Yeah.

Dr. Leonard Calabrese
Can actually do harm. And it

Dr. Mark Hyman
Like marathon runners.

Dr. Leonard Calabrese
And and beyond. Now we have people Ultra marathon. Ultra marathon runners. You know, and it's I don't think it's coincidental, and I'm sure you've seen this in your practice. I've seen many people who have developed, you know, what we would recognize now as chronic fatigue syndrome, who had started out as very high endurance athletes, and then something has fallen apart, and you just wonder in your head of whether this was a predisposing factor, but we get people moving.

So there was a very interesting study done at the University of Colorado in the last, about eighteen months where they experimentally took a group of people who work at a sedentary, job, cubicle, sit there all day long, and they randomized them, to you get to go to a gym and come in a half hour late, and you do thirty minutes on the treadmill, versus, you, who all you have to do is for five hours during the day, get up and walk around five minutes out of each hour, five minutes out of each hour. And then they measured a number of outputs. And while they didn't do immunologic function, they looked at, vitality, well-being, mood, etcetera. The people who won were the people who were just getting up and moving. Walking around.

Yeah. You know, you don't You need

Dr. Mark Hyman
a step counter, the 10,000 steps.

Dr. Leonard Calabrese
All of that stuff that Mike Roysen talks about and that our whole enterprise engages in, you know, it's I think it's good for your body, it's good for your brain, and it's clearly good for your immune system. So it's just a a small bit of data. And, similar to what we talked about from the nurses health study in on diet, there have been several large epidemiologic studies to show that people who carry the predisposition to rheumatoid arthritis, who are more physically active, will have a lower incidence of actually developing the disease over a lifetime. So you've got two two areas that, you know, that there's clearly enough data for so many reasons.

Dr. Elroy Vojdani
Yeah.

Dr. Leonard Calabrese
Cardiovascular health, emotional well-being, and immunologic strength.

Dr. Mark Hyman
So what happens to your immune system when you exercise? Not not like the ultra marathoners, and I I know you've written about this where you see even even clinical studies looking at ultra marathoners versus regular folks, their immune system is different, their oxidative stress is more. What what is actually happening when you exercise your immune system?

Dr. Leonard Calabrese
It's actually still, relatively poorly understood. If you divide it into two two, types of studies, one are the studies where you can do it in a lab and come in and, you know, get on the do an exhaustive stress test or cycle till you've hit the oxidation wall, and, you're you're, you know, hit your aerobic capacity. There, it's not surprising, that all types of things happen to your immune system. You have trafficking of immunologic cells. You have elevations of inflammatory cytokines.

Those are the mediators that cause inflammation, and redistribution of lymphocytes like T cells and B cells. I've always said, well, I would expect that. That's just stress, and your immune system is moving to stress. The more important question is, if you take a person who's sedentary and a person who has moderate activity and a person who is an ultra marathoner, do their immune systems differ by what we have traditionally measured? T cells and b cells and inflammatory cytokines and the like?

And the answer is, there's very little difference that we can detect. And my response to that is is that, you know, we have very poor tools. Yeah. We're just now, you know, we're We're

Dr. Mark Hyman
looking with we're looking with an eyeglass instead of a telescope.

Dr. Leonard Calabrese
We're looking at the same techniques that we looked at, you know, forty years ago, where in the next five years, we'll be looking with, you know, what we recognize as ohmic technologies, where we're looking at the entire cloud of data, of how your genes are functioning, and, how your proteome and metabolome, so, some of that work is starting to be done right now, and, I I I look forward to seeing more of it.

Dr. Mark Hyman
That's pretty exciting. So it's eating, right, exercise. Let's talk about stress because I think the data is pretty clear that stress is not good for your immune system, but that the act of managing stress or actually doing things that help reset your stress response actually can help your immune system. And it's really the the conversation about molecules of emotion.

Dr. Leonard Calabrese
It it it really is. I think that this is the most exciting area going on in immune behavioral science right now, and the data that are being generated are, you know, pretty impressive. So let let's just talk about, let let me back up and and give you just a magic minute on on triggering the immune system. So, you know, we have this immune system here. It's designed to defend us from all types of dangerous signals.

We traditionally think of that as, external signals such as, you know, infections, and it certainly does all that. There is another set of danger signals that we are just now, starting to understand, and you brought up the term psychoneuroimmunology. And A mouthful. It is, it is, and it's your psyche, your nervous system, and your immune system. And, you know, we don't know what stress levels were, you know, 200, five hundred, five thousand years ago, but we do know that today living in this world, stresses are different.

You know, you got you know, you're carrying your phone in your pocket. I had to turn it off when I came in here, and I'm probably already getting nervous about how many emails are stacking up while I'm, having this nice conversation with you. The, you know, the exigencies of of modern life are are are complicated. Add to that the environmental stresses. You know, we're living in a world where, you know, the temperature is rising, pollutants, are bombarding our body.

Those are danger signals. Yeah. And so, there is a tonic level of stress there that I think is probably new in the industrial age. Processing that is our brain, by and large, And the brain can send signals to the body, that promote inflammation. You know, inflammation is good when you cut your finger.

It's bad when you have it for ten years. So, the immune system is triggered, by stress, to generate, accelerated inflammation, which contributes to all these immune mediated inflammatory diseases that we're talking about, contributes to acceleration of aging, and that includes aging of the immune system, and we have this great term called immunosenescence, you know, your immune Doesn't

Dr. Mark Hyman
sound good.

Dr. Leonard Calabrese
It does not sound good. Right. So so all of this is going on

Dr. Mark Hyman
dying of your immune system is what it means in English.

Dr. Leonard Calabrese
That's right. So, with that as a background, the question is, you know, what the heck do we do about it? Yeah. And all the And that

Dr. Mark Hyman
the science is really good about what happens to your immune system under stress. It's not

Dr. Leonard Calabrese
it's not

Dr. Mark Hyman
just an idea, oh, stress is bad for you. It's actually mapped out pretty well.

Dr. Leonard Calabrese
It's it's it's it's mapped out in in incredible detail, and we can look at people who have mood disorders, we can look at people who are caregivers, for patients with cancer or dementia, we can look at people with PTSD, we can look at all of these populations, and there's profound perturbation of their immune response. So how do we move that needle? How can we do that? Well, you know, there are a variety of techniques, but the ones that have been best studied surround the use of mindfulness meditation.

Dr. Mark Hyman
And,

Dr. Leonard Calabrese
I'd like to just take a couple minutes to talk about this with you, because I know that you're a great practitioner. And so, for those in your audience who are, many are well familiar with this, the cognitively based, mindfulness based stress reduction developed by Jon Kabat Zinn twenty five, thirty years ago has been the standard bearer of of, Research. Of research. And, you know, I give unbelievable credit, to his pioneering efforts and all the data that's been generated for this, but as you know, this is pretty demanding stuff. And, you know, day of introduction, you know, you have coursework.

And to

Dr. Mark Hyman
be stressed is hard work. Oh, I always

Dr. Leonard Calabrese
said if I had enough time for CBCT, I wouldn't be stressed. Mindfulness based stress reduction. I'm sorry, mindfulness based stress reduction. So, I've been asking the question for the past, number of years, whether lower doses of mindfulness can, have beneficial effects on all the domains that MBSR, has had effects on. Doctor.

Dr. Elroy Vojdani
So you

Dr. Mark Hyman
need an hour twice a day, maybe there's like a different dose. Doctor.

Dr. Leonard Calabrese
Maybe there's so, you know, we have a program that develops at the Cleveland Clinic, Stress Free Now. And Stress Free Now has been used in multiple settings and we've published in scientific literature, you know, when, you know, hundreds of engineers have taken this, people from call in centers that are all stressed out, that, fifteen minutes four times a week, appears to lower stress levels.

Dr. Mark Hyman
Fifteen minutes twice a week.

Dr. Leonard Calabrese
Fifteen minutes four times a week seems to be a sweet spot, which is, you know, that's doable. We've also developed a program, which you can get on your app, called Stress Free Now for Healers, and I designed this program.

Dr. Mark Hyman
God knows we need it.

Dr. Leonard Calabrese
You know, that we're talking about burnout and all the stresses of this, you know, I couldn't stand the thought of trying to tell some neurosurgeon he asked to meditate for an hour a day to reduce the stress, it probably caught me over the head, right? Right, so we

Dr. Mark Hyman
Nice you up with a scalpel.

Dr. Leonard Calabrese
We're introducing this smaller dose. So now, with this, so we know that it reduces stress, so now we have a study, that is going on. We just launched it, and we're getting scores of people interested in participating. We're doing it within our own system. So we're taking Stress Free Now for Healers, this low dose meditation that can be used on your app, it can be used, at your workstation computer, and, we're gonna take nurses who are undergoing occupational stress, and over a six week period we're going to study them, but the primary endpoint is not going to be reducing their stress.

The primary endpoint is we're going to look at how this affects how their genes function. So we're doing what we call next generation sequencing. We're looking at the entire function of the genome.

Dr. Mark Hyman
Doctor. So very high-tech analysis.

Dr. Leonard Calabrese
Very high-tech analysis. Doctor. And then we're looking at all these interleukins.

Dr. Mark Hyman
Doctor. Of inflammatory molecules. Doctor.

Dr. Leonard Calabrese
Of inflammatory molecules of the immune system, of the immune system, and it'll be the largest study done of its type. None has been done in the healthcare setting, none has been done with this low dose, and we just are so excited about working with this. And I will tell your audience, so if you're interested in following me, this work along and my kind of world view on this, you know, follow me on Twitter

Dr. Mark Hyman
Yes.

Dr. Leonard Calabrese
Lcalabre's d o, and, I would, you know, get my wild and wacky view of the immune system and behavior. But this is where we wanna go. We wanna plumb that. And, Mike Roizen and I have had this discussion that he thinks that we should be looking at six minutes, of mindfulness meditation. I don't know the the answer is, but that's where our studies are gonna be going in the future.

Dr. Mark Hyman
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