← The Dr. Hyman Show
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- [00:00]
Dr. Mark Hyman
Coming up on this episode of the Dr. Hyman Show.
- [00:03]
Dr. Will Cole
60% of your immune system is right underneath the lining of your gut. So 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 a 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.
- [00:25]
Dr. Josh Axe
Did you know that over 75% of people are deficient in magnesium? That's a problem because magnesium is essential for over 600 functions in your body.
- [00:33]
Dr. Mark Hyman
Including energy production, stress regulation and deep sleep.
- [00:36]
Dr. Josh Axe
Here's the catch. Not all magnesium is created equal. Most supplements only contain one or two forms. But magnesium Breakthrough by Bioptimizers gives you all seven essential forms in one capsule.
- [00:47]
Dr. Jeffrey Bland
So your body gets exactly what it needs, where it needs it.
- [00:50]
Dr. Josh Axe
I take magnesium breakthrough every night and I've noticed a huge difference in my sleep, stress and muscle recovery.
- [00:55]
Dr. Jeffrey Bland
It's a game changer.
- [00:57]
Dr. Josh Axe
Right now Bioptimizers is offering my listeners a special discount. Just go to bioptimizers.com hyman and use.
- [01:03]
Dr. Mark Hyman
Code HYMAN10@ check out. Don't wait. Your body will thank you plays a big role.
- [01:09]
Dr. Josh Axe
Now, before we jump into today's episode.
- [01:11]
Dr. Will Cole
I'd like to note that while I.
- [01:12]
Dr. Jeffrey Bland
Wish I could help everyone via my.
- [01:14]
Dr. Josh Axe
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.
- [01:22]
Dr. Jeffrey Bland
Well, you.
- [01:23]
Dr. Josh Axe
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, Dr. Hyman Plus. And if you're looking for curated trusted supplements and health products for your health journey, Visit my website Dr.hyman.com for my website store and a summary of my favorite and thoroughly tested products.
- [01:47]
Dr. Peter Attia
What are the things that help us have immune resilience? And what are the things that have changed in our environment or our life.
- [01:53]
Dr. Jeffrey Bland
Or lifestyle that have actually made our.
- [01:54]
Dr. Peter Attia
Immune systems be dysregulated?
- [01:56]
Dr. Chris Kresser
Yeah, 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 kind of balancing all the different sides, making sure that 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.
- [02:31]
Dr. Peter Attia
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. 80% 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, 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 gut's now linked to everything from psychiatric disease to cardiac disease to diabetes, metabolic health, cancer and obviously autoimmune disease and allergic disorders and asthma and 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 disease and it's not something that traditional medicine does a very good job of thinking about diagnosing or treating. And I've been involved in academic centers with these long Covid clinics and it's kind of embarrassing, honestly. All right. To see how little they know and.
- [04:01]
Dr. Jeffrey Bland
How little they're doing.
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Dr. Peter Attia
And yet there's so much that's known that we can actually do something about.
- [04:07]
Dr. Jeffrey Bland
We were just chatting a little earlier.
- [04:09]
Dr. Peter Attia
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 possible orthostatic hypertension syndrome. And we're seeing other autoantibodies against different tissues. And it's kind of scary and there's techniques to actually fix it and heal it. 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.
- [04:43]
Dr. Jeffrey Bland
And it's used for a lot of immune diseases.
- [04:45]
Dr. Peter Attia
So talk about if we had this problem with immune resilience, what are we seeing with that? We're seeing the rise in autoimmune disease. And can you kind of help us connect the dots between the decline in our immune resilience, the rise in autoimmunity, and then what's happened with this long Covid phenomena?
- [05:05]
Dr. Chris Kresser
Yeah, absolutely. So 25 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'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 center 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 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 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 prolonged congestion, you know, lots of secondary infections. You know, just. You're just seeing the immune system just completely failing. So 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 15, 20, 25 years down the road in a population that's dramatically suffering, and, you know, the current medical infrastructure has zero answer for this. You know, it's. It's. What other biologic medications can we come up with to try to, you know, kind of suppress, hinder, suppress, Right? And now we're getting to the point where, you know, we have patients with 3, 4, 5 autoimmune diseases and every biologic under the sun can't control what's going on with them. So it's a huge problem, it's progressive, and the only way that we're going to get out of it is to acknowledge that and to start making conscious choices that limit those continuous exposures to our gut.
- [07:42]
Dr. Peter Attia
So healing the gut is a big part of healing from autoimmune disease, for sure. That's been something I've done in my practice in functional medicine for 30 years in 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 having Covid, they did a study of over a million half people and was published in Nature.
- [08:05]
Dr. Jeffrey Bland
Out of the, you know, one and.
- [08:06]
Dr. Peter Attia
A half million people that they studied, in this study that was published in Nature, they found a 46% higher chance of getting an autoimmune disease, which is astounding. After having Covid.
- [08:15]
Dr. Chris Kresser
Absolutely.
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Dr. Peter Attia
So why, why is that happening?
- [08:18]
Dr. Chris Kresser
That's happening again because I think of the dramatic loss of immune resilience that we have as a population. So, you know, 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 6 to 12 month window after the infection. More and more studies are coming out showing that everything from rheumatoid arthritis, lupus, type 1 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 12 to 24 months or more. You know, 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.
- [09:46]
Dr. Jeffrey Bland
Yeah, no, it's so true.
- [09:47]
Dr. Peter Attia
And the symptoms for Long Covid are just astounding like this. 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, brain fog, autonomic dysfunction.
- [10:04]
Dr. Chris Kresser
And the scariest part of it, I don't know what you've seen recently, but I think the early batch of Long Covid was, was predictable. Those who were gonna get really severe or hospitalized forms of COVID they were gonna have really big struggles afterwards. Now it's like 45 year old dad walks into the clinic, metabolically healthy, not smoking, not a heavy drink, 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.
- [10:31]
Dr. Peter Attia
So is Long Covid and autoimmune disease in and of itself or is it just one of the aspects of it?
- [10:36]
Dr. Chris Kresser
Well, in the research that my dad and I have done on Long Covid so far, we've found specific autoimmunity, 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. 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.
- [11:03]
Dr. Peter Attia
Yeah, I mean, that's an important thing. I want you to unpack that, because what we're seeing with Long Covid is that dormant infections kind of rise up from the dead 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.
- [11:19]
Dr. Chris Kresser
Absolutely. So there are a large group of viruses that we, as adults, by the time we're adults, we've been exposed to, we've been infected with HHV6, 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 genius in their long term evolution against us. They have figured out how to evade complete immune eradication by hiding in tissue after the acute infection. But with a normal immune system, they stay in dormancy. They wouldn't dare step out into the wild and get eradicated by the immune system. But what we're finding is that the virus.
- [12:08]
Dr. Peter Attia
If you have a herpes cold sore.
- [12:10]
Dr. Chris Kresser
Exactly.
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Dr. Peter Attia
It only comes out when you're under stress.
- [12:12]
Dr. Chris Kresser
Exactly.
- [12:12]
Dr. Peter Attia
It's not there all the time, but the virus is there just sleeping. It wakes up when there's some kind of insult.
- [12:18]
Dr. Chris Kresser
Correct. Right. 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 their clinical symptom set 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.
- [12:53]
Dr. Peter Attia
And are there good diagnostics immunologically to help map out what's going on with these patients? Because, you know, long Covid is a bucket. But it's truly probably many, many, many different kinds of problems and each individual responds to the install with different manifestations and may need different kinds of treatments.
- [13:12]
Dr. Chris Kresser
Let's go over the buckets, if you don't mind.
- [13:13]
Dr. Peter Attia
Yeah, yeah.
- [13:14]
Dr. Chris Kresser
Right. So 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 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'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 going to have some unique spectrum. Of those five, though the majority will have, let's say three or four of them. So we don't have diagnostics for the mitochondrial part. Maybe on the research side there are.
- [14:21]
Dr. Peter Attia
Some things, but they're hard to get.
- [14:23]
Dr. Chris Kresser
They're very hard to get. Germany and like the seahorse analysis, I.
- [14:27]
Dr. Peter Attia
Use igl Lab in Germany that does a detailed mitochondrial assessment is mitoswab. It looks at mitochondrial stuff, but it's organic acids. But it's definitely hard.
- [14:35]
Dr. Chris Kresser
You and I know that stuff. Right. But not every physician out there in the United States. Right?
- [14:40]
Dr. Jeffrey Bland
Yeah.
- [14:40]
Dr. Peter Attia
These are sort of more functional medicine diagnostics that are not used in traditional medicine, but they're available.
- [14:45]
Dr. Chris Kresser
They're real for sure. The viral reactivation stuff, I think rather straightforward. Antibodies, IgM, IgG, antibodies to different targets of Epstein Barr virus, HHV, 6, CMV. There's no diagnostics for Covid persistence, if that is in case what's going on. I mean, you can look at 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 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, myeloologodendrocyte, glycoprotein, the blood brain barrier is a very common target that was demonstrated in mouse literature.
- [15:31]
Dr. Peter Attia
So you're basically seeing autoantibodies, basically your own immune system, attacking aspects of your brain, your brain tissue.
- [15:38]
Dr. Chris Kresser
The most important defense of your brain, which is the blood brain barrier disrupted in football players, boxers, Alzheimer's, Parkinson's. So 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.
- [16:03]
Dr. Peter Attia
And so these are lab tests that.
- [16:05]
Dr. Jeffrey Bland
You can do to help sort of.
- [16:06]
Dr. Peter Attia
Sort things out and tell which type of the sort of five buckets people go in.
- [16:10]
Dr. Chris Kresser
Yeah. You know, make an attempt to try to, you know, on this kind of early leading edge side of things, identify how much of each one of them they're dealing with.
- [16:19]
Dr. Peter Attia
I mean, you publish a lot on this. You publish in Nature, which is a major journal, and other journals looking at autoimmunity and the exposome and Covid.
- [16:26]
Dr. Jeffrey Bland
And I think, you know, it might be helpful for us to sort of.
- [16:29]
Dr. Peter Attia
Dig into sort of how do the sort of this persistence of long Covid symptoms, you know, what's the underlying biology that's happening here? Is it an overactivation of cytokines? 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.
- [16:52]
Dr. David Perlmutter
Yeah.
- [16:53]
Dr. Peter Attia
You know, how does it all set up put together for people?
- [16:55]
Dr. Chris Kresser
It's tough because it's multiple pieces. But if I was going to break it down to what I think the core of it is, the acquired mitochondrial damage and the associated lack of autophagy, to me is really core there. So mitochondria are 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. 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 you can see.
- [17:44]
Dr. Peter Attia
Brain's on fire.
- [17:45]
Dr. Chris Kresser
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.
- [18:00]
Dr. Peter Attia
That exists, you already have mitochondrial issues.
- [18:02]
Dr. Chris Kresser
Massive mitochondrial issues to begin with. Right. So that's why we're seeing a bigger problem with it here, both in the short term and the long term.
- [18:09]
Dr. Peter Attia
So just unpack that 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 into energy in the form of ATP that our body uses to fuel everything. So when you basically think about that, 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 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.
- [18:40]
Dr. Chris Kresser
Absolutely.
- [18:41]
Dr. Peter Attia
Because not a lot of people talk about the connection between the immune system and the mitochondria. What do we know about that?
- [18:46]
Dr. Chris Kresser
It's clear. So if mitochondria can run either on something called oxidative phosphorylation. Sorry for the fancy words, but you know, to.
- [18:56]
Dr. Peter Attia
It's burning carbs.
- [18:57]
Dr. Chris Kresser
Yeah, right. Burning oxygen and carbs. But that's an efficient form of, you know, converting food into energy.
- [19:06]
Dr. Peter Attia
It's kind of like a diesel truck.
- [19:08]
Dr. Chris Kresser
Yeah, right. Less fuel, more miles. 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 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, 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? It says, okay, we've got something we need to fight. It puts itself into fighting mode, which is a pro inflammatory mode. The nervous system, the glial cells know when macrophages, which are a kind of primal defense cell, are in this white blood cell or in this fight, and they will convert themselves into glial activation and put themselves into this neuroinflammatory fight response, all from the powerhouse of the cell. But that makes perfect sense.
- [21:03]
Dr. Peter Attia
It's a domino effect.
- [21:04]
Dr. Chris Kresser
Yeah, but it's the most important part of you. Of course that's gonna happen.
- [21:11]
Dr. Mark Hyman
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- [21:39]
Dr. Jeffrey Bland
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 because 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's this low grade chronic inflammation that we now refer to as inflammaging, the inflammation that occurs as we age and 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, um, 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, 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, immunorejuvenation is a relatively new concept. It was really sort of framed by my mentor, Jeffrey Bland. Dr. Jeffrey Bland, the father of functional medicine, was a student of Linus Pauling and 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, in the work that Jeff's doing, he's taught me most of what I know in medicine. So we have 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, immunorejuvenation essentially trains your immune system to work better at every level. Your immune systems turn over fast, your white cells turn over fast. You build a new immune system regularly. Everything comes from your BL and bone marrow, right? So your padic 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 develop these cells called zombie cells that, 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're kind of in a challenging moment in history for human immune systems. We are dealing with things we never had to deal with before. And the worst is our diet, which is a highly inflammatory diet, our processed food diet, high sugar and starch diet, high refined oils, la enough phytochemicals and medicines in food, and anti inflammatory compounds in food and omega 3 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 were also having increased spread of globalization of microbes through like we saw with COVID in 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 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 immunorejuvenation 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 our cells 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 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 Pacman, little things called lysosomes. Gobble up all the old cells or damaged cells or damaged proteins and digest them and break them down into component parts and then reuse them like recycling. And it's quite 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 a lot of the ways we can do it actually is through food and through the right nutrients in food and through the right phytochemicals in food. So we also have to actually understand how to also rejuvenate our mitochondria. Because our mitochondria are the energy factories of our cells. They're the places 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 mitophagy is 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 rej 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 is 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 they are in various kinds of foods. One of the most important foods for immuno rejuvenation is something called Himalayan tartary buckwheat. Now this is 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 Cor 10 we've seen reverse biological age and some preliminary data they've shown that using Himalayan Terry 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 problem. But the right amount of exercise actually helps build immunity. Also make sure you get the right omega 3 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 pro resolving mediators which are basically like breaks on the immune system and they also take out a lot of the important things like astaxanthin which is important for inflammation. It is an antioxidant that is found in a lot of the omega 3 fat containing fish like salmon. So want to make sure you have the right Omega 3s. 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 a lot of them out there. We've talked a lot about it on the podcast, but we want to make sure including pre and probiotic foods. Also get rid of all the junk, right? The processed food, fried foods, sugary foods, junk foods. These are 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 stre, it 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 and repair systems. So it's really important and I think there's a lot of ways to do this. So, and 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 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 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 Dr. 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 hesperidin. All these bioflavonoids that are, that are found in food that can really rejuvenate our immune system. And they, they, they're found in abundance in this Himalayan tari buckwheat. The second is eating the, the right am omega fats, omega 3 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 3s from it and keeping the pro resolve and mediators preventing the degradation is purified. There's no toxins in it, it's cold processed so it retains all its benefit. And it's quite a different omega 3 fat. The next is your microbiome and this is supporting your microbiome through pre and probiotic foods. And actually Himalayan tari buckwheat has these amazing microbiome supporting fibers that are quite amazing. And basically you want to make sure you get these from all sorts of foods. Not just obviously Himalayan tartary buckwheat, but omega 3 fats from fish, polyphenols from plants, fibers and premium probiotics 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 30 minutes at you know, 170 degrees, a regular sauna for 30 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 or 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.
- [35:26]
Dr. Josh Axe
Not overeating.
- [35:26]
Dr. Jeffrey Bland
And actually having a diet that is, is time restricted can be very important. So donate three hours before bed, give yourself at least, you know, 16 hours, maybe 12, 14 if you're, you know, thin and you can't tolerate a longer period. But most people can deal with a 16 hour overnight fast. That's eating dinner at 6 and having breakfast at, you know, 10 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 kind of puts you out of your comfort zone, 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 3 fats. So that's a great way to really think about reshaping your immune system to actually deal with the ravages of aging and inflammaging, but also to boost it so you can actually fight infections and cancer.
- [37:03]
Dr. Will Cole
60% of your immune system is right underneath the lining of your gut. So 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 a 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.
- [37:27]
Dr. David Perlmutter
Yeah. You know, I'm glad you brought that up and diving into the science just a little bit. I mean, the microbiome, 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're immunodeficient, and we know that from animal models, we know it from people we know a lot about. And you had Dr. Hazen on the show study this in the most robust scientific way possible. We know what a healthy microbiome kind of looks like. Diverse and rich. We've yet to dial it in to this organism, that organism. So we know that good diets, people that eat real food, usually have a more diverse, enriched microbiome, and that supports immunologic health. I'm reluctant to tell people. Carl Sagan used to say that extraordinary claims require extraordinary data.
- [38:45]
Dr. Peter Attia
Evidence.
- [38:45]
Dr. David Perlmutter
Right. And so 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 a huge effect on.
- [38:59]
Dr. Will Cole
The frame of functional medicine. We often people call on elimination diets which is eliminating inflammation 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 saying?
- [39:14]
Dr. David Perlmutter
Absolutely, yeah.
- [39:15]
Dr. Will Cole
All right, so next topic would be.
- [39:16]
Dr. Jeffrey Bland
You said exercise.
- [39:17]
Dr. David Perlmutter
Exercise. So I've been interested in exercise and immunity for decades. Actually 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. And last year we had David Niemann 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.
- [40:12]
Dr. Will Cole
Being a couch potato is bad for your immune system.
- [40:14]
Dr. David Perlmutter
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 and we just talk about.
- [40:22]
Dr. Will Cole
Heart disease and things like that, but this is a whole new view.
- [40:26]
Dr. David Perlmutter
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 months, you know, walking is an incredible form of immunologic strength building and we actively endorse. And 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 training for ultramarathons at the other end? No matter where you are? We try to move people down a bit at a time. And Betsy and I, nurse practitioner, world's best nurse practitioner, we talk to our patients about instant recess. That's what we call. And we Say, you know, if you are 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 the first time I did this at a scientific meeting, these guys are like, what's going on here? 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. And, you know, you can. Too much of something is often as bad as not doing it. And there have been a lot of epidemiologic evidence to show people who are ultra exercisers can actually do harm, like marathon runners and beyond. Now we have ultramath, ultra marathon runners, you know, and 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 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 18 months where they experimentally took a group of people who work at a sedentary job cubicle, sit there all day long, and they randomize them to. You get to go to a gym and come in a half hour late, and you do 30 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, et cetera. The people who won were the people who were just getting up and moving, walking around. Yeah, you know, you don't.
- [43:57]
Dr. Will Cole
You need a step counter the 10,000 steps.
- [43:59]
Dr. David Perlmutter
All of that stuff that Mike Roizen talks about and our whole enterprise engages in. You know, 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 small bit of data. And similar to what we talked about from the Nurses health study 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 but two areas that there's clearly enough data for so many reasons. Cardiovascular health, emotional well being and immunologic strength.
- [44:49]
Dr. Will Cole
So what happens to your immune system when you exercise? Not like the ultra marathoners, and I know you've written about this where you see even clinical studies looking at ultra marathoners versus regular folks. Their immune system is different. Their oxidative stress is more what is actually happening when you exercise your immune system.
- [45:05]
Dr. David Perlmutter
It's actually still relatively poorly understood if you divide it into two types of studies. One are the studies where you can do it in a lab and come in and do an exhaustive stress test or cycle until you've hit the oxidation wall and, you know, hit your aerobic capacity. There's 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 that, you know, we have very poor tools. We're just now we're looking with an.
- [46:29]
Dr. Will Cole
Eyeglass instead of a telescope.
- [46:30]
Dr. David Perlmutter
We're looking at the same techniques that we looked at 40 years ago, where in the next five years we'll be looking with what we recognize as omic 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 look forward to seeing more of it.
- [46:56]
Dr. Jeffrey Bland
That's pretty exciting.
- [46:57]
Dr. Will Cole
So 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 conversation about molecules of emotion.
- [47:18]
Dr. David Perlmutter
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 pretty impressive. So let's just talk about. Let me back up and give you just a magic minute on triggering the immune system. So 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 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.
- [48:11]
Dr. Will Cole
Mouthful.
- [48:12]
Dr. David Perlmutter
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, 500, 5,000 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, are stacking up while I'm having this nice conversation with you. The exigencies of modern life are complicated. Add to that the environmental stresses. We're living in a world where the temperature is rising, pollutants are bombarding our body. Those are danger signals. 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. Inflammation is good when you cut your finger. It's bad when you have it for 10 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 system doesn't sound good. It does not sound good. Right. So all of this is going on.
- [50:07]
Dr. Will Cole
Dying of your immune system is what.
- [50:09]
Dr. Peter Attia
It means in English.
- [50:10]
Dr. David Perlmutter
That's right. So with that as a background, the question is, you know, what the heck do we do about it?
- [50:17]
Dr. Jeffrey Bland
Yeah.
- [50:18]
Dr. Will Cole
And I think the science is really good about what happens to your immune system under stress. It's not just an idea. Oh, stress is bad for you. It's actually mapped out pretty well.
- [50:26]
Dr. David Perlmutter
It's mapped out 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. And 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 of are well familiar with this, the cognitively based mindfulness based stress reduction developed by Jon Kabat Zinn 25, 30 years ago has been the standard bearer of research, of research. And 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 day of introduction, you know, you.
- [51:48]
Dr. Will Cole
Have to be stressed is hard work.
- [51:51]
Dr. David Perlmutter
I always 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. All right, so you don't need an.
- [52:28]
Dr. Will Cole
Hour twice a day. Maybe there's like a different dose.
- [52:30]
Dr. David Perlmutter
Maybe there's. So 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 when hundreds of engineers have taken this people from call in centers that are all stressed out, that 15 minutes four times a week appears to lower stress levels. 15 minutes twice a week, 15 minutes four times a week seems to be a sweet spot, which is. That's doable. We have also developed a program which you can get on your app called Stress Free now for Healers. And I designed this program.
- [53:15]
Dr. Will Cole
God knows we need it.
- [53:17]
Dr. David Perlmutter
You know, we're talking about burnout and all the stresses of this. So I couldn't stand the thought of trying to tell some neurosurgeon he has to meditate for an hour a day to reduce his stress. He'd probably club me over the head, right? So.
- [53:33]
Dr. Will Cole
So icy up with a scalpel.
- [53:35]
Dr. David Perlmutter
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, can be used at your workstation computer. And we're going to 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.
- [54:27]
Dr. Will Cole
So very high tech analysis, very high tech analysis.
- [54:30]
Dr. David Perlmutter
And then we're looking at all these interleukins, inflammatory molecules, inflammatory molecules 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 this work along and my kind of worldview on this, follow me on Twitter. Yes, El Calabrese do and I would get my wild and wacky view of the immune system and behavior, but this is where we want to go. We want to 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 answer is but. But that's where our studies are going to be going in the future.
- [55:27]
Dr. Mark Hyman
If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr. Mark Hyman please reach out. I'd love to hear your comments and questions. Don't forget to rate, review and subscribe to the Dr. Hyman show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on the Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness center, my work at Cleveland Clinic and Function Health where I am Chief Medical Officer. This podcast represents my opinions and my guests opinions. Neither myself nor the podcast endorses the views or statements of my guests. This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding.
- [56:14]
Dr. Jeffrey Bland
That it does not constitute institute medical.
- [56:16]
Dr. Mark Hyman
Or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're Looking for a functional medicine practitioner? Visit my clinic, the Ultra Wellness center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health. This podcast is free as part of my mission mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.
- [56:51]
Dr. Jeffrey Bland
Are you feeling stuck on your health journey?
- [56:53]
Dr. Mark Hyman
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