Don't Wait for Alzheimer's — A Neurologist's 30-Year Plan to Protect Your Brain

By the time memory begins to slip, the changes affecting the brain may have been developing for decades. But the trajectory isn’t fixed, and many of the factors driving it are within our control. In this episode, I sit down with my longtime friend and mentor Dr. David Perlmutter, six-time New York Times bestselling author whose new book, Brain Defenders, rethinks what it really takes to protect the brain as we age. You’ll learn: Why protecting your brain should begin long before memory problems appear How your daily choices influence whether the brain’s immune cells shift into a protective or damaging state Which numbers to know now, including fasting insulin, blood sugar, and waist-to-hip ratio How food, exercise, sleep, gut health, and environmental toxins shape your brain’s future What emerging research reveals about slowing—and even improving—cognitive decline I’ve always appreciated how David’s work replaces fear with something far more useful: a clearer understanding of how the choices we make today can help protect our memory, independence, and quality of life for years to come. View Show Notes From This Episode Sign up for Dr. Hyman’s Brainshaping Academy to learn how to nourish the biological systems that support your mental, emotional, and cognitive health https://drhyman.com/products/brainshaping?utm_source=dr_hyman_show&utm_medium=newsletter&utm_campaign=may_27&utm_content=link Get Free Weekly Health Tips from Dr. Hyman https://drhyman.com/pages/picks?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Sign Up for Dr. Hyman’s Weekly Longevity Journal https://drhyman.com/pages/longevity?utm_campaign=shownotes&utm_medium=banner&utm_source=podcast Join the 10-Day Detox to Reset Your Health https://drhyman.com/pages/10-day-detox Join the Hyman Hive for Expert Support and Real Results https://drhyman.com/pages/hyman-hive This episode is brought to you by Paleovalley, Pique, Perfect Amino, BON CHARGE, Cozy Earth, and Fatty15. Shop nutrient-rich foods and supplements at paleovalley.com/hyman and save 15% off your first order. Elevate your daily wellness ritual at piquelife.com/hyman and enjoy 20% off plus free gifts. Help fill protein gaps at bodyhealth.com and use code HYMAN20 for 20% off. Explore red light products at boncharge.com/hyman and enjoy 15% off with code HYMAN. Upgrade your sleep setup with cozyearth.com and enjoy 20% off with code HYMAN. Head to fatty15.com/HYMAN today and use code HYMAN for 15% off your 90-day subscription Starter Kit.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  When we recognize that 40 to 50% of adults in America who live to be age 85 will have a diagnosis of Alzheimer's disease. At 65 years and older, risk is 1 in 9 or 11% of people age 65 or older have dementia. It is almost a fully preventable situation that people shouldn't fear, that people should feel empowerment as it relates to making the right choices.

• 0:30Dr. Mark Hyman?

  One of the biggest mistakes people make with protein is thinking it has to be complicated. The truth is consistency matters more than perfection. Having simple ways to add protein throughout the day can make a huge difference. That's one reason I keep Paleo Valley's grass-fed vanilla bone broth protein on hand. Yep, I add it to smoothies, but what I really like is how versatile it is. You can mix it in a coffee or use it in baking when you want an easy protein boost that actually tastes good. And with Paleo Valley's sweet and savory options, it's easy to work bone broth protein into all kinds of everyday foods and drinks. It's made from 100% grass-fed and grass-finished beef bones and provides collagen-rich protein that fits easily into a whole food lifestyle. Now, when healthy habits are simple, you're much more likely to stick to them. And this is one that's been easy for me.

• 1:16Dr. Mark Hyman?

  Keep protein simple, go to paleovalley.com/hyman to save 15% off your first order today. One of the questions I get all the time is, what's the healthiest way to boost your energy? Here's the truth, many people depend on coffee to get through the day, but for a lot of people, it can become part of the problem. Coffee can contribute to jitters, energy crashes, cravings, disruptive sleep, and increased stress on the already overworked system. And that's why I've been enjoying Sun Goddess Matcha from Peak for years. At a time when demand for high-quality matcha has created shortages around the world, Peak continues to source some of the purest ceremonial-grade matcha available. It delivers a calm, sustained energy thanks to its natural combination of caffeine and L-theanine, helping support focus and productivity without that roller coaster that so many people experience with coffee.

• 2:00Dr. Mark Hyman?

  And what I also love about matcha is it's packed with powerful antioxidants that supports healthy aging, metabolic health, and radiant skin. And for an even more powerful longevity ritual, I add Peak's Carrera Marine Collagen. Carrera combines premium marine collagen, biotin, and pearl powder to support skin elasticity, hydration, hair, nails, and the whole body vitality. Together, they create a simple morning ritual that helps you feel energized today while investing in your long-term health. To experience Sun Goddess Matcha and Carrera for yourself, visit peaklife.com/hyman to exclusively receive 15% off for life. That's P-I-Q-U-E, life.com/hyman. David, welcome back to the podcast. So good to see you again. And I know you're coming in from British Columbia, which is exciting.

• 2:43Dr. Mark Hyman?

  And I think you're taking well-deserved rest before the launch of your new book, Brain Defenders, which I'm very excited about. How to harness the power of your immune cells to protect your brain for life. We're going to get all into that and go deep on this because it's really an important topic. You know, David, I think, you know, we've known each other for, I don't know, 30 years now. And you were one of my mentors. You originally taught me so much about the brain. And I was recollecting about the original book that you had written that helped me understand Parkinson's, mitochondria. And you were the first one to talk about this idea of the brain on fire.

• 3:19Speaker 00

  That's right.

• 3:20Dr. Mark Hyman?

  And you had this really crappy slide.

• 3:23Speaker 00

  All of our slides were crappy back in the day.

• 3:27Dr. Mark Hyman?

  At the conferences, and it really stuck with me. And that so much of what's wrong in the brain, whether it's neurodegenerative diseases or mood disorders, the whole spectrum of brain dysfunction is in some ways tied to dysregulation of immune function and immunity and inflammation of the brain. And your new book goes really deep on this. So maybe you can kind of start out by helping us understand a few things. Why are you focusing now on this whole framework of immuno-metabolism, the mitochondria and the immune system interacting in the brain as the root cause of so much of what we're seeing that's wrong in today's brains?

• 4:06Speaker 00

  Well, Mark, this represents, I think, for me, a significant convergence of everything that we've been talking about for such a long time. And it's incredible because it really unifies the mechanisms that we've talked about. You mentioned the brain on fire. This embraces the idea that neuroinflammation is a central player in what makes a good brain go bad. But beyond that, well, then where does the inflammation come from? And it comes from exactly what you described, those microglial cells, these brain immune cells, innate brain immune cells. Who knew that the brain had its own immune system? And, you know, we tend to think about, well, that's what makes a good brain go bad.

• 4:49Speaker 00

  And the reality is, these cells are, I hate to say designed, but what they're, what they do on a good day is maintenance and good things. They maintain our synapses, they maintain the function of the neurons, they maintain the blood-brain barrier. So it really broadens the scope of what we would classically consider to be immune function. When you ask somebody, what does the immune system do? And the response is going to be, well, that's what comes into play when there's a challenge, by a bacterial infection, viral infection, surveillance for cancer cells, whatever it may be. But the reality is that, you know, these firemen in the firehouse are doing a lot of work to maintain the fire engine when there's no fire. And I think that tends to broaden our understanding of this immune system.

• 5:34Speaker 00

  It has a good side and a downside. And to be very technical about it for our discussion today, these microglial cells can exist either in a very supportive, we call it the M2 rule, where they're shoring up these barriers and keeping our synapses working. Or they can shift to being destructive, what I call in the book, the evil twin, the M1 configuration, where they are going around and destroying the synapses, creating that neuroinflammatory environment where the neurons can't work well anymore and the blood-brain barrier becomes more permeable, letting bad things into the brain. And that said, the most empowering part of our discussion today

• 6:18Speaker 00

  is that the shift from being supportive to being destructive is under our control. And, you know, for me, that really represents a whole heck of a lot because it explains everything we've been talking about for so long. It explains why, you know, in brain brain, why a higher carb diet, and we'll unpack this today, is associated with activation of these microglial cells. It explains why permeability of the gut, for all, you know, of all things, from having changes in our gut bacteria leads to increased inflammation that will activate these microglial cells and shift them to becoming, again, the evil twin.

• 6:59Speaker 00

  We now see that we can, research-wise anyway, image the brain in living humans using what's called a TSPO scan. This scan images when the microglia are activated to their destructive state. So a positive TSPO scan shows activation of the microglial cells. And we see that the TSPO scan is positive, as you would expect in Alzheimer's, in Parkinson's, in multiple, multi-system atrophy, progressive super nuclear palsy, major depressive disorder, post-traumatic stress, and even long COVID.

• 7:40Speaker 00

  So really, this whole notion of activation of the brain's immune cells, called microglia, throws an incredibly large net. And that is giving us all a level of empowerment now that we've never had access to in the past.

• 7:57Dr. Mark Hyman?

  You know, I think, I think there's a whole new way of thinking about the brain. I think we've kind of lost this essential idea in medicine, which is that we can help the brain. We know we can prevent heart disease by lifestyle. We know we can prevent diabetes by lifestyle. I mean, we even know in some ways cancer can be prevented by reducing toxin exposure and helping with your metabolism and a lot of other things. But brain health is just something that we, we think of as this black box and that traditional medicine doesn't know what to do with. It's like, okay, well, I hear so much of this from my friends who have family members with Alzheimer's. And they go, well, I don't want to know my test because there's nothing I can do. There are this fatalistic view that the brain is fixed

• 8:41Dr. Mark Hyman?

  or it progresses towards disease with this inexorable path that can't be altered. And in this, with some point about your work and the things that you highlighted, you know, decades ago and that you continue to work on, is that the brain is changeable, that the brain can be influenced by what we're doing, by our microbiome, by our diet, by exercise, by sleep, by our nutritional status, by reducing exposure to environmental toxins, by helping our mitochondria work better. There's so many pathways to actually improving brain function and not only just slowing, preventing neurodegenerative diseases like Alzheimer's or Parkinson's, but actually intervening and reversing many of them. And that's kind of a, kind of a heretical thing to say in medicine.

• 9:22Speaker 00

  It's what you just said. You're right. It's considered heretical. But as our colleague Dale Bredesen has mentioned many times, we all know of cancer survivors. Do we know of any Alzheimer survivors? And now we're starting to see that happen. And it's really based upon what you just described, and that is these metabolic inroads. And that is what you originally teed up for our conversation today, this concept of immuno-metabolism, immuno being what we're talking about, these microglial cells in the brain, the brain's immune cells, and their metabolism. So when these immune cells shift their metabolism, when their metabolism changes, then they shift in becoming the evil twin.

• 10:06Speaker 00

  They shift from being supportive to being destructive. It's all predicated on their metabolism that changes. Their mitochondrial function is declining suddenly and rapidly, and that induces this shift to becoming what we call M1 and destructive. And here's the take on bullet point message, and that is that the metabolism of the microglial cell mirrors the metabolism of your body.

• 10:34Speaker 00

  Wow, that is incredibly empowering. So if I dedicate my lifestyle choices to improving my body's metabolism, to keeping my weight down, to keeping my blood sugar in check, to keeping insulin functionality where it needs to be, to keeping my blood pressure where it should be, then I am actually working lovingly with my microglial cells to really become the architect of my brain's destiny. And, you know, in my case, having a family history of Alzheimer's, it's what I need to do. And I am certainly not alone in that. When we recognize that 40 to 50% of adults in America who live to be age 85 will have

• 11:17Speaker 00

  a diagnosis of Alzheimer's disease, tells me a couple of things. Number one, that's a flip of a coin, and I want to make sure it lands on the right side for me and for everyone I'm interacting with. And number two, we should absolutely consider this to be an epidemic. That segment of our population is the most rapidly expanding. And when you look at those statistics in terms of Alzheimer's risk, I mean, at 65 years and older, risk is 1 in 9 or 11% of people age 65 or older have dementia. I will say here on your podcast, it is almost a fully preventable situation that people shouldn't fear, that people should

• 11:59Speaker 00

  feel empowerment as it relates to making the right choices. It's an awful situation for certainly the patient and for the loved ones as well. Having been through that, you know, I, again, I want to dedicate everything I do to giving people this information that this does, we can rewrite your brain's destiny.

• 12:18Dr. Mark Hyman?

  I think that's important, David. This is such an important concept, that we can do stuff to keep our brains healthy, functioning, and mentally sharp. And the question is, you know, I'm 66, you're a little bit older than me, not too much, and you're like, little ahead of me, like my big brother.

• 12:32Speaker 00

  71.

• 12:33Dr. Mark Hyman?

  71, you're my big brother, you know, like, how do we keep our brains healthy for the next 20 years? So, we're thinking about it for ourselves, but it's, it's really an important concept of what causes brain damage, what can I do differently now to make sure I stay mentally healthy and my brain stays healthy and I have no neurodegenerative diseases over the next 20 years? And what should I be measuring and looking at in my own biology to track what's happening? And this is important for us to sort of unpack, I think, because, you know, we know that the changes happen in the brain decades before you ever forget your keys, or somebody's name, or, you know, get lost in a grocery store. These are things

• 13:15Dr. Mark Hyman?

  that happen, you know, in their 30s, 40s, 50s, before you see any changes in people's 60s, 70s, and 80s. Can you help us understand, what are those things we should really be thinking about in terms of what is causing brain damage? And how do we stop that? How do we, how do we stop this fire in the brain that you've been so elegantly describing for decades? And this, this kind of, how do we optimize our metabolism, reduce inflammation, and all these core concepts? Because we know now so much more than we did even when we all started this 30 years ago, that it's, it's really doable.

• 13:46Speaker 00

  Well, I think the most important step is that you embrace the idea that you are in charge. If you don't do that, then, you know, you're not going to pursue the other things that we will now talk about. So, really, job one is, I am the architect of my brain's destiny. Okay, Dr. Perlmutter, Dr. Hyman, what do I do? That's your question. And the reality is, it's not difficult, it's not really that sophisticated. If, what makes a good brain go bad across the entire spectrum of neurodegenerative conditions, yes, we're fearful of Alzheimer's, but there's a long list of other, of other things that can make a good brain go bad, that's for sure. I mean, you know, people don't realize that Parkinson's

• 14:29Speaker 00

  is also influenced by metabolism. If you have type 2 diabetes, your risk of Parkinson's is increased by 85%. So, this notion that metabolism is important is, you know, the answer to your question, we've got to do everything we can to remain metabolically intact. In our 40s and 50s, we have a big buffer there cognitively, such that we don't really see the cognitive changes in the brain until, you know, maybe we're in our 60s, maybe we are in our 70s and are forgetful of our keys, Wi-Fi codes, grandchildren's names, et cetera. We're way down the continuum of brain decline when that stuff starts to

• 15:11Speaker 00

  happen. And you're exactly on point, that the issues that sow the seeds for the brain's degeneration happen when we are a lot younger, in our 30s and in our 40s. That's who I'm hoping are listening to our conversation today, because that's when we really begin to establish our personal set points as it relates to metabolism. That said, to answer one other part of your question, then what are those markers? And they are very straightforward, simple markers that you've talked about for years. How important is your fasting blood sugar for your brain's destiny? It is fundamental. Know your fasting blood sugar. And that is something, as need I tell you, you don't need a doctor's prescription to understand

• 15:56Speaker 00

  your fasting insulin level, your A1C.

• 15:58Dr. Mark Hyman?

  I know, I know, another doctor talking about protein, but stay with me for a second, because what matters isn't just how much protein you eat, it's actually whether your body can actually use it. As we age, we naturally lose muscle and become less efficient in absorbing and utilizing protein. There's actually a term for this, anabolic resistance. And that's why I add Perfect Amino to my smoothie every morning. Gives you all nine essential amino acids in a highly adorable form that supports muscle protein synthesis and health, maintain muscle and bone health as you get older. And unlike many whey proteins can spike insulin levels similar to sugar, Perfect Amino's does it. Plus, it can help you hit your protein goals without adding a lot of unnecessary calories. So if you want to learn more, head to bodyhealth.com and use the code HYMAN20 for 20% off your

• 16:42Dr. Mark Hyman?

  first order. That's bodyhealth.com and use the code HYMAN20. Most of us are walking around in a state of chronic stimulation. Your cortisol is elevated, your nervous system is stuck in go mode, and we wonder why we can't sleep or focus. And one thing I've been using that I generally look forward to at the end of the day is the infrared PMF wrap from Bone Charge. PEMF, otherwise known as post electromagnetic field therapy, delivers gentle electromagnetic frequencies into the body that mimic what you naturally absorb spending time on the earth. Combined with red and near-infrared light, it's one of the few recovery tools that works while you're absolutely doing nothing. I throw it on for 30 minutes on reading or winding down, and I notice I sleep

• 17:24Dr. Mark Hyman?

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• 17:44Speaker 00

  Want to take it a little deeper? Let's look perhaps at your C-reactive protein. And as I describe in the book, there are a suite of very brain-specific blood tests that we can get, like PTOW 217, which we could talk about. But the main players are those blood tests that I mentioned that look at your blood metabolic markers, know your blood pressure, and buy a very, very sophisticated and expensive tool called a tape measure, and put it around your belly, and put it around your waist, and then do the math and determine your waist to hip ratio. And, you know, this is an extremely valuable way of

• 18:28Speaker 00

  understanding what is your risk? How does that relate? Well, when your belly is big, you have more visceral fat and you're increasing inflammation. Those microglial cells in your brain that are in charge of whether your brain will be healthy or not, call it like it is, are very receptive to inflammation coming from anywhere in the body. When inflammation chemicals, called cytokines, are produced anywhere in the body, like from a leaky gut for all who knew, right? Those chemicals can make their way to the brain through the blood-brain barrier that becomes less and less functional as we age. Those microglia

• 19:08Speaker 00

  see inflammation and they shift to becoming the evil twin. Now that they're shifted to becoming the evil twin, they go around the brain and destroy synapses. The main issue in the Alzheimer's brain that leads to decline in cognitive function is the loss of connection, one neuron to the next via the synapse, that's the connection. So, at a microscopic level, it's a loss of connection. At a macroscopic level, Alzheimer's patients lose connections with themselves, with people around them, and with their entire environment. So this loss of connection is really, you know, kind of the central issue that is involved in

• 19:51Speaker 00

  the Alzheimer's brain. But, you know, we lose connection in Parkinson's as well. We lose connection of these cells that make dopamine in the part of the brain called the substantia nigra, projecting to other motor areas. And it's the same mechanism. That was demonstrated by Dr. Langston in the 1980s, when he first saw these patients who used a designer IV drug that was contaminated, the microglia were activated in their brains immediately, and destroyed those cells that made the dopamine. And immediately, they got Parkinson's. And he studied their brains 13, 14 years later, and these microglia were still at it, still destroying tissues. So, this is, you know, Science Technology Magazine

• 20:36Speaker 00

  called this the number one discovery of 2025, the incredibly central, centralized role of microglia in brain degeneration. And

• 20:48Speaker 00

  Gratefully, it's great to have another explanation, finally, that takes us away from this idea that, for example, Alzheimer's is caused by, ask anybody, they'll tell you what causes Alzheimer's, the accumulation of beta amyloid in the brain. I think my blood pressure just went up saying that because I'm really getting tired of hearing it and reading. I read it last night in some news report that what can we do to lower beta amyloid? That is absolutely not the cause of Alzheimer's disease. I say that in the book, provide the data, explain how the whole amyloid hypothesis was flawed. But when we look at that discussion through the lens of these new amyloid targeting drugs,

• 21:32Speaker 00

  they are not working. If beta amyloid is the cause of Alzheimer's, then you would think getting rid of the beta amyloid might do some good. A Cochrane analysis was published about two months ago. This was an analysis of the 17 top studies that evaluated the effectiveness of the drugs that do indeed lower beta amyloid in the brain. The study that involved 20,342 individuals, each study lasting about 18 months, looked at two things, risk and benefit. That's what we always do, right? To determine, are we going to write a prescription for something, an intervention? What's the risk and what's the benefit? What they found was the benefit

• 22:14Speaker 00

  was zilch. That's not the word they used. The word they used was trivial. They don't work. And the risk was really high. 20 to 25% of these people on these drugs develop brain hemorrhages, brains and/or brain swelling, or even death. And for a drug that doesn't work. So that's a powerful argument against putting people on these $40,000 a year intravenous infusions every two weeks. And the response when I, when I challenged doctors who are doing this therapy is, well, we've got to do something.

• 22:51Dr. Mark Hyman?

  There's nothing else to do.

• 22:52Speaker 00

  Yeah, we've got to do something, got to offer something. Well, you're offering something that is very threatening and has no efficacy. So that, that raises the hair on the back of my neck. And so what do you do in a situation like that? You write a book.

• 23:07Dr. Mark Hyman?

  Thank God. I mean, one of the things I think, you know, you hinted at a little bit, which I think is important to double back on, is this really important idea that all the conditions that happen to the brain, Alzheimer's, Parkinson's, ALS, MS, long COVID, pharamalager, chronic fatigue, mood disorders, psychiatric disorders, they're all related. They may manifest differently in different people based on their particular unique genetics or predispositions, but the fundamental mechanisms underneath all these things are very similar. And they have to do with our, our inputs, right? The things that we have control over, our diet, our lifestyle, exercise, stress, sleep, all that, environmental toxins,

• 23:50Dr. Mark Hyman?

  our microbiome. And then the downstream effect is very similar dysfunctions around inflammation, around mitochondrial dysfunction, metabolic dysfunction, you know, oxidative stress. These are all things that we actually have been talking about for decades in functional medicine. And we're down in, into the, you know, into the kind of weeds of things, looking at these diseases, rather than kind of zooming out and saying, okay, what do they have in common? What can we do to optimize our overall health, but particularly our brain health, you know, from this lens? And that's what we should be focusing on. And I think, you know, the, you know, this is a very powerful modality. I read a patient who had pretty significant dementia. We really helped her in so many ways. She had heavy metals. She

• 24:35Dr. Mark Hyman?

  had methylation issues. She had gut issues. We fixed a lot of things. And she kind of did really well for quite a while. Then she had a decline because her husband died. It was a big loss for her. And I said, well, why don't we just try a ketogenic diet? And this might have been 20 years ago. Because, you know, I was reading about the literature and mitochondria and inflammation and insulin resistance to the brain and type 3 diabetes, which would be Alzheimer's. And I was like, let's try it. And it was, it was amazing. You know, the family was wealthy enough to have a chef. They gave her the food and it was like she woke up. And, you know, it lasted for quite a while. And it just, it just alerted me to the fact that even in people who are fairly down the road, there are things that can be done to really help this. And as you mentioned, you know, Dale Bredesen is talking

• 25:19Dr. Mark Hyman?

  about the Alzheimer survivors. You know, who's an Alzheimer survivor? Nobody, right? But there are now people, and I've had them in my practice as you have, that when you aggressively treat these factors, the causes, you optimize the immune system, you optimize mitochondria, metabolic function, that these people do better. And it's quite remarkable.

• 25:40Speaker 00

  Yeah, you bring up a really good point. I don't want to miss this while it's still in our minds. And that is, that you mentioned mitochondria multiple times, and that is the metabolism of these microglial cells. And ultimately, when the microglial cell shifts from being supportive to being destructive, it actually is characterized by a loss of mitochondrial function. The M1 destructive microglial cell does not use mitochondria to any significant degree. It's using glycolysis. So its energy production is much less efficient, much less ATP produced. So in a very real sense, all of those neurodegenerative conditions

• 26:21Speaker 00

  that you listed are mitochondropathies are based upon failure of their mitochondria. You can get there from mold exposure, from having insulin resistance, from head trauma, from exposure to environmental toxins, from PM 2.5s in the, in the air that we breathe, which is certainly very important right now, vis a vis the incredible fires that we're seeing across North America. And, and you're right. And when we target the mitochondria, we get, we get responses like you've described and I have seen, and certainly Dale Bredesen has described as well.

• 26:56Dr. Mark Hyman?

  Well, there was something really new that you said in your, in your book that I thought was so striking, that I hadn't really thought about before, which is that the microglia basically are the immune cells in your brain. And they have mitochondria. And I never thought of how the mitochondria in the immune cells affect the function and health of the, of the immune cells. And that was a kind of an aha for me, like, wait a minute, the metabolism, aka mitochondria, of the immune cells, when it goes awry, is what's causing so much of the brain inflammation and the brain on fire that we've talked about for so long. And it's contributing to all these neurodegenerative and neuropsychiatric disorders. Is that right?

• 27:37Speaker 00

  Immunometabolism. What a term.

• 27:39Dr. Mark Hyman?

  So talk about this. I think this is a new, a new idea. I mean, Jeff Blandis talked about it, one of our friends and mentors, but like, tell us about what, what is this? And is this kind of a new idea? And how do we start to think about it? How do we start to act on it and even diagnose it?

• 27:54Speaker 00

  It's important because it's certainly not just these microglial cells in the brain, but it's immune cells throughout the body that are dysregulated when their metabolism goes awry. And let me make one point that I think is really important. This is bidirectional. That when these immune cells are targeted by glycated proteins, elevated blood sugar, toxins, inflammatory cytokines, it will then shift their metabolism. It will reduce their mitochondrial function. At the same time, as mentioned a moment ago, when mitochondrial function is challenged for other reasons, then the immune cell will be targeted as

• 28:36Speaker 00

  well and shift to being less supportive. So it's a bidirectional support system. Immunometabolism support, you know, goes both directions. And the manifestations of dysregulated metabolism of our immune cell is seen throughout the body. But the central and pivotal role as it relates to the brain, I think, is so powerful because we can influence it deeply by targeting metabolism, targeting the things that I mentioned, you know, the markers of metabolism that we can easily measure. When we do that, we are absolutely targeting our, our brain's immune cells, these microglial cells, to be back on our side and back to being supportive.

• 29:17Speaker 00

  And as we've talked about, this is the upstream mechanism, well above the accumulation of alpha-sulfur nuclein or beta amyloid or other proteins that people tend to want to focus on, even phosphorylated tau. The phosphorylation of tau happens, which is, for your viewers, phosphorylated tau, P tau 217, which is the blood test you can get, you know, doing function health, for example, you can go and get your P tau 217 measured, is a very valuable indicator of loss of synapses. If you really want to know what it's telling you, the higher the level of this P tau 217, a blood test, that is an indication of loss

• 30:00Speaker 00

  of synapses. It is therefore, and what is causing loss of the synapses, activation of the microglial cells. So this is a very important, and now arguably, a more specific blood test, you know, in distinction, a contradiction to the simpler blood test that you and I talked about earlier. So in a very real sense, you're, you're evaluating what in the heck's going on in your brain's immune system when you look at that test. But as I mentioned earlier, it can be as simple as measuring your waist-to-hip ratio.

• 30:35Dr. Mark Hyman?

  Yeah, I think this is important. Let's kind of double down on this because I think this is a really, this is really new information for people, which is, up till now, we didn't really have a good way of like checking your blood sugar of your brain. In other words, what is your, like, diabetes? Oh, my blood sugar is high, I've got diabetes. Or my blood pressure is high, I've got high blood pressure. But we didn't have a biomarker or a set of biomarkers that we could look at that would be impacted by lifestyle.

• 30:58Dr. Mark Hyman?

  You know, we could check your APOE4 gene, which gives you a risk of Alzheimer's, but those are genes that can't be changed. You can change the expression of them. But now we have biomarkers that are really revolutionary, I think. It's like, it gives us an opportunity to start to look at people's blood work very early and see what are the progressions and what are the changes and how do we modify those? Because it's not just finding this lab work and going, oh shit, you know, I got this problem. It's like, oh, wow, I have this problem. My blood sugar is a little high. Maybe I should stop eating bread and sugar. You know, maybe my P tau 217 is high. Maybe I should change my lifestyle. Maybe I should eat better. Maybe I should reduce my insulin resistance so I can improve my metabolic health. Maybe I should look at my microbiome and help that.

• 31:43Dr. Mark Hyman?

  Maybe I should look at my toxic load and things that might be triggering this. Maybe I should exercise more. Maybe I should focus on my sleep a little better. Maybe I should think about nutrients I could take that would help my mitochondria or help my regulate my immune system or my microbiome. So it gives you an opportunity to think about creating a plan for yourself that's very proactive instead of reactive. I mean, by the time you are in end-stage Alzheimer's, there's not a whole lot you can do. But early on, you can see a lot of things changing. And then I've been actually using these tests. And in Function Health, we now offer a full suite of tests that include, as your basic panel, a lot of things you were mentioning. Insulin resistance markers, insulin A1C, particle size, hormone levels, toxin levels, nutritional levels, home assistant, all the

• 32:28Dr. Mark Hyman?

  things you'd want to look at as a foundation. But we also offer an advanced sort of brain panel, which allows us to look at P tau 217, amyloid AD 4240, looking at neurofilament light chain, which is often, you know, damaged when the brain's damaged from traumatic vein injury and other injuries, and G-fap, which is another protein. So there's a lot of things you can look at. And so I think for me, it's a really empowering moment in neurology. And, you know, I mean, I'm going to make fun of you. You're a neurologist, but the joke we had about neurologists in medical school was diagnose and adios. Basically, you would just, you would be great at diagnosing things, but there was nothing you could do about it.

• 33:06Speaker 00

  It is so true. And, you know,

• 33:08Dr. Mark Hyman?

  And now it's not like diagnose and adios is diagnose and olá, como estás? Let's go.

• 33:14Speaker 00

  Well, for me, it's, I want to be intervention long before we diagnose. And, you know, I think what you just described is really fundamentally important, that the standard of approach in medicine has been to treat illness once it has manifested. And what you're describing is the approach of keeping people healthy in the first place, which is more valuable. I mean, I would, I would submit, it's absolutely the latter. And, you know, we describe our healthcare system in America. It's nothing to do with health. It's treating illness. And so this is very much preemptive, preventive approach that you were describing, and it's very, very empowering. And I remember back in the day, this thought came, came to mind

• 33:59Speaker 00

  again, early on in the PSA blood tests, prostate specific antigen, insurance wouldn't cover it unless you had a diagnosis of prostate cancer. Early on in the PSA, before your time, sunny boy. But anyway, and I thought, how ridiculous is this? And then there was a notion of breast cancer prevention. And, you know, wear the pink ribbon, all this. And breast cancer prevention was really emphasizing the way to prevent breast cancer is to let women get mammograms all over the place, you know, every year have, or whatever the interval was, have a mammogram. Mammograms don't prevent breast cancer. Excuse me. They

• 34:39Speaker 00

  early detect breast cancer. So I think that what you're describing, and in fact, that suite of blood tests that you described, you know, the agglial fibular, the GFAP, the neurofilament light, NFL, the looking at phosphor related tau, P tau 217, we described them in the book because they're available to people and they do give you a sense as to where you begin the process. And, and, you know, people talk about, well, what about your genetics? And what if I do carry the APOE4 allele and I know therefore, if I'm heterozygous, I have a five-fold increased risk. If I have two of them homozygous, my

• 35:19Speaker 00

  risk for Alzheimer's may increase 12-fold. Should people even know that? And my answer is, you bet 100% because that will be much more encouragement for you to do what Mark Hyman and I are talking about today. And that is get busy and get your metabolism, get your metabolic house in order, and you can absolutely rewrite your destiny. And that's what this is all about. And, and it, does it fly in the face of modern medicine, how medicine's practiced here in America? Yes, indeed, it does. I mean, you know, we see how the deck is stacked and that's okay. I mean, Robert Kennedy, senior once said,

• 36:00Speaker 00

  some people see things as they are and ask why. That's what we're doing right now. Others see things as they could be and simply ask, why not? And that's what we're doing as well. Why not? Why not give people the tools to set the stage for a healthy brain now and not have to suddenly awaken at age, at my age, 71, and notice some cognitive issues and then hope for a cure? Do I hope for a cure, a pharmaceutical cure for Alzheimer's? 100%. If that existed, if GLP-1s turn out to be effective, I'm going to sign up for that. You bet. I will, I will be recommending that. And I talk about that in the book.

• 36:41Speaker 00

  I, you know, my mission is not to really think outside of the box. It's really to make the box more inclusive. And I am open to a drug intervention. You bet I am. And having mentioned GLP-1s, I think there is some promise there. But for now, let's do the metabolic work.

• 36:58Dr. Mark Hyman?

  Yeah, I think it's so important. And the name of your book is so important, Brain Defenders, because it talks about how do we defend our brain? Like, what are the things we can do to defend our brain? And right now, I think people don't really know, like, you know, if I, I shouldn't smoke and I should manage my blood pressure and I should, you know, not eat too much saturated fat and I should exercise to prevent myself from getting a heart attack. But if you ask people, what should I do to prevent getting Alzheimer's? It would be pretty much a black box for people. So I'd love to sort of spend a bunch of time

• 37:27Speaker 00

  You hear much of what you just said. Go ahead.

• 37:30Dr. Mark Hyman?

  Well, it's those things too. Yes. It's like, the good news is, God treats, anything treats everything. You know, it's kind of like, kind of a joke. But if you look at the fundamental reasons we get sick, there's only a few. It's what we eat. It's our lack of activity. It's stress. It's lack of sleep or poor sleep. It's environmental toxins. It's changing our microbiome. It's our genes combined with all those things to determine who we are. And, and those things are highly modifiable. And we can't change our genes or we can change the expression of those genes. And so let's talk about like the fundamental things that people can do other than looking at these, these causes, right? Looking at the blood tests, which helps you see where you are. What are the things that people should

• 38:12Dr. Mark Hyman?

  be doing to help their immune metabolism, to help their brain immune system, to help their metabolic health, both with their body and their brain? Because I, I mean, the brain and the body are the same. Like, it's not like we have, we talk about the body, mind, mind, body. This is one thing. It's not like two things. So I think that we kind of get all confused about that. But I think we really need to think about, you know, what are those things that people can, can do very practically that have the most impact on the brain? And maybe you can kind of walk us through what you, what you discovered around how to optimize immune metabolism related to the brain.

• 38:45Speaker 00

  You bet. And, and again, you know, so many things came to mind when you, in that setup. And first, you know, back in the day, there was a heart smart diet. Remember the heart smart diet? As if, well, I don't have heart disease. I have another situation. So I shouldn't go on that diet. No, it's a body systemic good diet to be on because it's involved with keeping blood sugar where it needs to be and lowering inflammation. And those are the keys. Those are the keys for brain health too, when we talk about diet. But the big, number one, most important thing is to embrace the idea, again, that you are in charge, that your decisions matter in terms of your brain's destiny. All right.

• 39:27Speaker 00

  Now, where are those, what are the decisions? And I'm not going to rank them, but I'll just go through them. Let's first talk about exercise. You know, when we look at the data that looks at levels of, let me preface this by, by the, a study appearing in the Lancet in 2024, that looked at 14 modifiable factors and indicated that attention to these 14 modifiable factors is associated with about a 50% reduced risk for developing dementia. And by and large, these modifiable factors are the things we've already talked about that affect metabolism. Interestingly, as a kind of a sidelight, they did not mention

• 40:10Speaker 00

  diet. They did not mention nutrition. So I, along with Dr. Robert Lustig, wrote a letter to the Lancet, led to the editor, saying, hey, you know, must have been oversight. Here are the references that describe diet, you know, the mind diet, various diets intervention, Mediterranean, and their effects on Alzheimer's risk. And we got a letter back from Lancet saying, well, thank you very much, but we're not going to publish your letter to the editor. So I don't know what's going on with that. We'll leave that. But let's, let's first talk about exercise. So, you know, the data that relates regular exercise with reduced risk of cognitive decline is vast. And, you know, that really came to us in, in actually

• 40:55Speaker 00

  the late 1980s from a Dr. Kirk Erickson, who randomized a group of just over 100 individuals. One group stretched, one group aerobically exercised.

• 41:06Speaker 00

  After one year, he did two things. He did a cognitive assessment and he actually did three things. He measured their B D N F. We'll talk about that in a minute. And he actually measured the size, using an MRI, of their memory center in the brain. And he was first to demonstrate that this intervention, this program that you put people on, was associated with an increase in size of the brain's memory center, a preservation, in fact, an improvement of cognitive function, just because these people exercise. You know, the epidemiological studies looking at people based on their self-reported exercise has shown strong relationship to reduction with more exercise of a risk of cognitive decline.

• 41:51Speaker 00

  And as we look at interventional trials, your friend Rudolph Tanzi at Harvard, along with Dean Ornish, published a study last year demonstrating an interventional trial on 51 individuals, not a huge trial, over a 20-week period of time, demonstrating that when they changed people's diets, allowed them to exercise regularly, or invited them to exercise regularly, reduced their stress. These are individuals with Alzheimer's disease diagnosed, that their cognitive function didn't slow in its decline. By and large, it stopped declining completely.

• 42:34Dr. Mark Hyman?

  That's crazy.

• 42:35Speaker 00

  And in fact, this is in 70% of their interventional people. In many of them, it had actually improved. I'm gonna let that one hang for just a minute. So, you know, getting back to exercise, the question I think that you and I are often asked is, okay, I get that being sedentary is bad for my brain, you know, sitting around, not doing things. And it's important to exercise. One question is, well, what's better then for my brain? Is it aerobic or is it resistance? Is it, you know, the weightlifting or the bands or whatever machine you might use at the gym? Or aerobics? And that was actually looked at in a journal called Clinical and Health Psychology in 2025.

• 43:18Speaker 00

  A study that looked at, was a review of 36 interventional trials, where they put people on these programs. And it was close to 6,000 individuals. And their conclusion was, is it aerobics? Is it resistance training? Their conclusion was, it is both. It's the combination that seems to work best. And, you know, as you and I know, these types of interventions work a little bit differently. That when we do resistance training, we're building muscles, which is really important because muscle tissue is an endocrine gland secreting various chemicals that ultimately positively influence brain health. So the muscles make chemicals that go elsewhere in the body, therefore it's an endocrine gland,

• 44:01Speaker 00

  more involved in, you know, regulating metabolism. The aerobic part of the story improves blood supply, improves insulin functionality. So it's the combination. And what Zhang and the other researchers in that report noticed was that the best bang for the buck, in other words, the best response, was in individuals who were 65 or older, you and me. And also, those individuals who already had some cognitive impairment.

• 44:34Dr. Mark Hyman?

  Yeah.

• 44:34Speaker 00

  For brain preservation, cognitive preservation, and even as a therapeutic intervention, exercise is really, you know, one of the fundamental legs of the stool.

• 44:45Dr. Mark Hyman?

  Great. Well, I worked out in the gym this morning at 7:00 and I went for a hike up the mountain. So like I got my, I got my exercise in. My brain feels good. During the summer, when I'm moving between work and everything else, life throws at me. I notice pretty quickly which clothes actually stay comfortable and which ones don't. That's exactly why I've been wearing Cozy Earth's All Day Tee so much lately. It's made with viscose from bamboo and still feels great even after a busy day. I've noticed the same attention to quality with their pajamas and their sheets, too. Everything from Cozy Earth just feels lighter and more comfortable. And honestly, when something feels good enough that you stop thinking about it completely, you realize how much those small daily comforts actually matter. Now, this summer, Cozy Earth's All Day Tee and Rib Knit Pajama Set have become two of my favorites.

• 45:30Dr. Mark Hyman?

  Find yours at cozyearth.com/hyman and receive 20% off. Let me tell you a secret about doctors. We're skeptical of most supplements and we should be. Many of them are backed by strong science and a surprising number of supplements don't actually contain the ingredients they claim to have. So it means something when I tell you that I take it every day and recommend it to my patients. From the moment I looked at the research, it was different. Over 150 peer-reviewed studies, 60-plus patents, an excellent subco-trust score of 9.8, more than a decade of subaliment, and the product itself is simple. One active ingredient, C15, that strengthens your cells to support healthy aging. Don't take my word for it. Look at the science. It's all published at discoverc15.com. And that's what convinced me to take it every day.

• 46:15Dr. Mark Hyman?

  And that's what'll convince you too, I think. Head to fatty15.com or slash hyman today and use the code HYMAN for 15% off your 90-day subscription starter kit. So David, let's talk about a few other things around diet and what is so crucial to understand for people as they bring a healthy diet. And I think we've talked about this a lot, but I think it'd be good to just crystallize your thinking about this in 2026.

• 46:39Speaker 00

  What I endeavor to do in Brain Defenders is simplify. Because as you well know, there are so many diets out there, whether it's Mediterranean, Mediterranean Plus, added greens, the MINE diet, you know, diets named after people, Paleo, Primal, whatever it may be. And I wanted to look upon diet, not so much in terms of what you should be eating day in and day out by being prescriptive about that, but rather what is the effect of the diet that you choose? But with some stipulations. And I think most importantly, it's a diet that's going to control your blood sugar. And I will say that we've got to get some metrics here. And I'm all in favor of wearing a continuous glucose monitor, not all the time, but from time to time,

• 47:24Speaker 00

  to get a sense as to what is this diet I have chosen for myself doing in terms of controlling my blood sugar? Because my blood sugar is fundamental in terms of controlling my microglial cells and therefore charting my brain's destiny. So get a sense as to the foods you're eating. Make choices that are reflecting a better control of your blood sugar. That said, I like a more plant-based diet. Doesn't have to be fully plant-based, but a diet that is colorful, meaning a lot of different colors of fruits and vegetables on the plate, giving you the polyphenols, giving you importantly, the dietary fiber, that fat we described should be healthful fat,

• 48:09Speaker 00

  not fat that is threatening to your body, to your brain, as if the brain were not part of your body. So I really did my best to simplify. We talk about why it's good not to eat later in the evening to increase that window of fasting and all of the things that people are very familiar with. But it's the outcome that is measurable of your dietary choices that I think doesn't, the outcome doesn't get as much attention as it needs. And that's what I focused on in this book.

• 48:38Dr. Mark Hyman?

  Yeah. And also, I think, you know, one of the things that people are understanding now about neurodegenerative disease in general, whether it's Alzheimer's or Parkinson's or even things like MS, they're often related to changes in the microbiome and gut dysfunction. And maybe you could kind of talk about that because you wrote a whole book about that. But I think it's worth sort of double-clicking on that again for people to understand how important keeping your microbiome healthy is because that's what's determining a lot of inflammation in your system, making control and affecting some resistance. If there's bugs in there that are not friendly bugs, it can affect you by producing toxic metabolites that affect the brain. So can you kind of talk about,

• 49:21Dr. Mark Hyman?

  a little bit about the microbiome and the brain in that context?

• 49:25Speaker 00

  You bet. And you're right. You know, I wrote a book years ago called Brain Maker. And to be fair, some of my colleagues were not, you know, the eyebrows went up. What do you mean? You know, the microbiome affecting the brain? That's the gut. That's, you know, the brain's in Chicago and the gut is somewhere south of Los Angeles. And so, yeah, it was an interesting time. But now I think the mechanisms have been, you know, much more fully fleshed out, delineated that we can understand, you know, the fundamental relationship between what's going on in the gut, even beyond the microbiome. But let's just talk about that for a moment. So I think one of the fundamental tasks of the microbiome, aside from the metabolites that these bacteria and other organisms produce,

• 50:10Speaker 00

  is maintenance of the lining of the gut. And as my friend Mark Hyman used to say, probably still says, you know, it's the garbage dump in the gut. That's the term you use. And things should stay in the gut that remain in the garbage and they shouldn't make their way into systemic circulation. Remember, you used to say that.

• 50:28Dr. Mark Hyman?

  I definitely did at some point.

• 50:31Speaker 00

  No, I think I remember when you did say that. But the point is that there's a lot of stuff in the gut that needs to remain there. And it stays there because we have really good protection. We have a strong barrier that keeps that stuff from making its way into the systemic circulation. The maintenance of that barrier is predicated on diversity and good functionality of our microbes in the gut, called the microbiome. When that is challenged by any number of issues that we can discuss, then they are less able to do that job, less able to maintain that barrier function. Things get out from the gut into the systemic circulation and even into the gut lining, the outside of the gut, and challenge immune cells.

• 51:14Speaker 00

  What do these immune cells do now that they are challenged with various chemicals like LPS? People may have heard of that, lipopolysaccharide. They increase their production of these inflammatory cytokines. If we go back to our original conversation early in this interview, we remember that cytokines, these inflammatory chemicals, make their way to the brain and stimulate our microglial cells to shift from being supportive, brain defenders, to being destructive. That connects an awful lot of dots between the microbiome being changed and ultimately paving the way for Alzheimer's, Parkinson's, other neurodegenerative conditions.

• 51:56Speaker 00

  To the extent that there is now publication, publications allowing us to recognize that we can almost fingerprint the gut microbiome and relate it to risk for neurodegenerative conditions of very specific types. That's how far we've come in studying the makeup of the organisms and more importantly, what they are producing. In other words, the technical term is the metabolomics of what is going on in the gut. But let me just extend this a little bit further. The most powerful influence on the makeup and functionality of the microbiome are the foods that we choose to eat.

• 52:38Speaker 00

  So now we've added one more dot, one more step, fundamentally relating our food choices to our brain's destiny. Now, it's through, now the lens of the microbiome that you teed up so eloquently. And having said that, it then allows us to understand why it is, one nuance, of the clear and present threat posed by our consumption, widespread consumption of these ultra-processed foods. We live in a country where, in adults, 60% of calories are coming from these Frankenfoods, is the term you've used in the past, these ultra-processed foods that represent a clear

• 53:21Speaker 00

  and present danger to your brain's destiny. Consumption of these foods, one study that was published in the Journal of Prevention of Alzheimer's, can you imagine a journal of prevention of Alzheimer's? Be still my beating heart. And this study that came out last year followed a group of 1,111 individuals over a period of 12.7 years and basically asked these folks during this 12.7 year, during the period of time that we're going to study you, what do you eat? So they kept a food frequency diary. What did they find? They found that those individuals who consumed, as an average, one serving per day of ultra-processed

• 54:04Speaker 00

  foods experienced a 13% increased risk of Alzheimer's disease, a disease-

• 54:10Dr. Mark Hyman?

  Just one serving, whoa, that's not much.

• 54:12Speaker 00

  That's a handful of chips. That's 13% increased risk of Alzheimer's, a disease for which there is no pharmaceutical treatment available, as you and I have this conversation. Further, they found that in those individuals who consumed 10 or more servings of ultra-processed foods a day, now that's in the, in the context of a country where 60% of our calories is coming from-

• 54:35Dr. Mark Hyman?

  Yeah.

• 54:36Speaker 00

  So that's not out of, that's 10 servings of chips.

• 54:40Dr. Mark Hyman?

  That's probably on the low end.

• 54:41Speaker 00

  Yeah. Their risk has increased 270%. That's of a disease for which we have no meaningful pharmaceutical treatment, so-

• 54:54Dr. Mark Hyman?

  270%.

• 54:55Speaker 00

  Yeah, basically a threefold increased risk of getting Alzheimer's, which, you know, if you live to be 85, as mentioned, is already a flip of a coin. Now you've really tipped the scales out of your favor. And that's just based on food choices. And so what do the ultra-processed foods do? They threaten blood sugar regulation, they threaten insulin functionality, they are pro-inflammatory, and they mess up your microbiome. Be that be, the discussion we just had, we know that's bad. When, you know, the microbiome is threatened, back to that, it's not only the gut permeability issue, but it's the lack of production of certain metabolites, products of these bacteria

• 55:36Speaker 00

  that make their way to the brain, these short-chain fatty acids that are important for gene expression regulation. What did I just say? That our gut bacteria are regulating our gene expression, our life code? I better take good care of my gut bacteria because they have a big, they have a very important job. They are determining gene expression throughout my body and yes, even in my brain, for crying out loud. So, so yeah, food matters.

• 56:04Dr. Mark Hyman?

  I think you're, what you're saying is so important and people don't realize how, how just dramatic diet can be in prevention and also treatment. And, and you know, you've written a lot about it, I've written a lot about it. I think one of the things that I think would be really worth sort of diving into a little bit is, is something that people don't really think about that much, which is, how do we, how do we think about the immunometabolic effect of toxins? And they're ubiquitous and they're everywhere. We're exposed to so many of them and yet many of us don't really have a way of sort of understanding how to diagnose them or treat them. And, and we feel a little bit confused because it's like, well, what do we do? And I think, I think you and I have both been involved in this field and, and I think

• 56:47Dr. Mark Hyman?

  that having a, a understanding of how to assess environmental toxic load, how it affects the brain, how it affects metabolism, how it affects immune function is really important. I, I think that was one of the biggest ahas I had early on was that toxins can be directly poisonous, but they can also be immunotoxic. In other words, they can trigger immune dysfunction. And there's all phenomena of autogenes, which are autoimmune-inducing toxins. The same can be true for the brain, I think. So maybe you can sort of help us understand that a little bit.

• 57:16Speaker 00

  Well, you know, we don't put this microglial activation in the category of classic autoimmunity, but in a very real sense, it is. These microglia are activated and then go about destroying our own tissue. So in a very real sense, I think it's fair to, to indicate that this is, you know, it's not a classic description, but it is an autoimmune situation. I think, back to your question though, how does a toxic exposure relate to this? And I think the, in a word, fundamentally. So I don't know how, how deep you want to go, but whichever toxin comes to mind, I think let's, let's look at toxins that are directly affecting the mitochondria.

• 58:01Speaker 00

  I recently had the opportunity, I think you did too, to interview Dr. Ray Dorsey. I think you had him on your podcast.

• 58:05Dr. Mark Hyman?

  Yeah, yeah, yeah.

• 58:06Speaker 00

  And he, he made it very clear that he considers Parkinson's, for example, to be a man-made disease as a consequence of, first, the industrial revolution and our exposure even back in the 1800s, when James Parkinson wrote his treatise on, on the, the shaking palsy is what his book was about. And he didn't describe what was, you know, it was a toxic event, but this was when people began to be exposed to these higher levels of toxins and even to this day. And, you know, by and large, the toxins that are at play here are toxins that threaten mitochondrial function.

• 58:46Speaker 00

  When we threaten mitochondria, we threaten the microglia and cause them to shift to becoming the evil twin. It's really that straightforward. We're threatening metabolism and this is again, the term immunometabolism, the relationship between mitochondrial dysfunction and this dramatic life-threatening change of our microglial cells, our brain's immune cells. So what Dr. Dorsey made very clear is that we are exposed to a variety of toxins these days in our environment that directly target mitochondria and therefore can manifest as things like Parkinson's. As you discussed in your interview of Dr. Dorsey, he's really very much fixated on

• 59:31Speaker 00

  this trichloroethylene, which had been used in industrial cleaner, dry cleaning fluid, makes its way into water, you know, and there are places where groundwater is still contaminated by TCE. And, you know, in my, in my lecturing, I've opened up this discussion a little bit further, looking at first, something I alluded to earlier, this MPTP contaminant of this IV drug that people were using in the 80s and getting Parkinson's because MPTP targets the mitochondria. Well, are there any mitochondrial toxins that we may be exposed to these days? And the answer is, you bet there are. Let's talk about something called paraquat. What is paraquat? Paraquat is an herbicide.

• 1:00:16Speaker 00

  It's used to kill weeds around our crops. The good news is that 70 countries around the globe, because it is such a devastating toxic experience, exposure to paraquat, have banned or significantly reduced the use of paraquat in agriculture. The country that is not on that list is the United States. In the United States, our usage of paraquat, a mitochondrial toxin, is skyrocketing. The reason being that, that our weeds in, that are less responsive now to glyphosate. We, so we, they're developing what's called Roundup Resistance.

• 1:00:57Speaker 00

  So we've had to turn to the use of paraquat, a mitochondrial toxin.

• 1:01:04Speaker 00

  Exposure to which is associated with increased risk of Parkinson's to treat the weeds in our modern agriculture. And let me be really clear about this paraquat thing. Paraquat is used experimentally to create Parkinson's in primates in research laboratories. And we are spraying it on our food. Something, uh, something's wrong here. Something's very, very wrong. That we are, you know, it's been said that man is the only animal who will be foul his own nest. So, you know, we're spraying a mitochondrial toxin on the food we eat. Something's wrong with that. Taking it even further, glyphosate itself, the active ingredient in Roundup.

• 1:01:48Speaker 00

  Buy it at the hardware store and, you know, spray it around your vegetables. I'm telling you not to do that. Uh, is similarly a mitochondrial toxin. And we're seeing the politic around glyphosate currently, and we'll see how that ends up playing. But, you know, we live in a toxic world. It's, it's true. And let me just pivot a little bit here to something I think that's really fairly germane as you and I are having this discussion in the summer months where wildfires are rampant in North America. Recognize that, you know, these are by and large forests that are on fire, but, uh, it, it's not like this smoke is benign when it's coming to our cities and we are breathing this.

• 1:02:32Speaker 00

  These particles, these PM 2.5s are powerfully pro-inflammatory, meaning they increase the cytokines in our bodies that make their way to the brain and will shift our brain defenders, microglial cells to becoming brain destroyers. Uh, and, and also, uh, the PM 2.5s themselves can be inhaled and make their way through the nose into the brain directly and can induce inflammation. Takes me to one other topic I want to cover real quickly and then we can unpack whatever else you want. And that is a, what we call a feed forward cycle. That inflammation experienced from any source, be it the permeability of the gut, be it

• 1:03:14Speaker 00

  the PM 2.5 particles that we might inhale, inflammation from any source will shift the microglia to becoming their M1 destructive phenotype, we call it. That is a pro-inflammatory phenotype, meaning that once those microglia shift to being the evil twin, and let's be clear, they can turn back. That's what our work is all about. But once they're in that M1 damaging configuration, they are spitting out more and more of these damaging cytokines in the brain that further target other good microglial cells and shift them to being on the dark side, if you will, like zombies. So it becomes a feed forward process.

• 1:03:57Speaker 00

  So you can induce that shift from, from head trauma, for example. That's why these football players with chronic traumatic encephalopathy, encephalopathy continue to worsen once they've stopped, uh, you know, after playing football. Look at Muhammad Ali, quit boxing, stopped the head trauma, but continues to worsen. Once this process, uh, has taken hold, it's a feed forward.

• 1:04:20Dr. Mark Hyman?

  Hard to stop. It's hard to stop.

• 1:04:22Speaker 00

  But not, but not impossible to stop. Can very well be stopped as you've demonstrated in your patients in whom you've improved their cognitive function, as Dr. Bredeysen has demonstrated, as I'm describing, as Dr. Tanji, uh, and, uh, described in his recent publication, you bet.

• 1:04:38Dr. Mark Hyman?

  And people are doing this. I mean, at our center, Ultra Wellness Center in Lenox, Massachusetts, we do a lot of this and we see these patients and we understand how to assess their nutritional status, insulin resistance, metabolic health, immune health, to look at mold, to look at toxins, to look at the microbiome. I mean, that's one of the big advances of functional medicine is, is really understanding how to optimize the microbiome to what we call the five R program as a reset for the gut. And, and these are just a, a different set of lenses and a different set of tools we use to address these kinds of chronic, often very quite scary illnesses, but, but we can really make a difference. And I think, you know, your work has just been so inspiring for me, or this book is incredible. I encourage everybody to get a copy of it, Brain Defenders.

• 1:05:20Dr. Mark Hyman?

  And, and the subtitle of this amazing book, Brain Defenders, is Harness the Power of Your Immune Cells to Protect Your Brain for Life, which is what you have to do. Um, before we close, David, I'd love to just do a rapid fire set of questions. You up for that?

• 1:05:32Speaker 00

  Are these double valued, two points each? Yes. Go ahead.

• 1:05:37Dr. Mark Hyman?

  Okay. What's the single worst daily habit for your brain health?

• 1:05:40Speaker 00

  I would say lack of connection. Lack of connection to others. Yes.

• 1:05:46Dr. Mark Hyman?

  I like that. And just as a side note, there's a, my new book that I'm sort of working on, I talked about this guy, Steve Cole, who's come up with this whole science of how disconnection and loneliness, uh, actually activates a whole gene expression pattern that drives inflammation. So it's, you're right on target. Um, what's the single best daily habit for brain health?

• 1:06:09Speaker 00

  Connection to others.

• 1:06:10Dr. Mark Hyman?

  Okay, there we go. How about alcohol? Is it ever good for the brain?

• 1:06:14Speaker 00

  It's never good for the brain. Uh, you know, our messaging has changed over the years. Never, it's a, it's a toxic event and it's never good for the brain.

• 1:06:24Dr. Mark Hyman?

  How about sleep? How many, how many hours should people sleep every night?

• 1:06:27Speaker 00

  Ideally, seven to eight, not just quantity, but I think it's important to study your sleep, wear the Apple Watch or the Oura ring and get a sense as to the quality of your sleep.

• 1:06:38Dr. Mark Hyman?

  You kind of addressed this a little bit, but what's more important for the brain? Aerobic exercise or strength training, if you had to pick one?

• 1:06:43Speaker 00

  If I had to pick one, I would probably say aerobic.

• 1:06:46Dr. Mark Hyman?

  And then walking. Is walking enough or do you need to do more?

• 1:06:50Speaker 00

  It really depends on the individual. What does walking do for you? Can you brisk walk and get your heart rate up to where it needs to be? That's the question. But I think walking on an incline is, you know, going to help build muscle mass, which is important as well.

• 1:07:02Dr. Mark Hyman?

  Yeah. If you're a marathon runner, walking probably won't do it, but if you're a couch potato, it probably would start. How about blood tests? What's the most important blood test that people are not getting, but they should?

• 1:07:12Speaker 00

  Fasting insulin.

• 1:07:13Dr. Mark Hyman?

  Agreed. Agreed. Wow. We're on the same page, David.

• 1:07:17Speaker 00

  If Mark Hyman agrees with me, I'm doing well.

• 1:07:20Dr. Mark Hyman?

  What's another thing that makes it bad in the long run for your cognitive health?

• 1:07:24Speaker 00

  Increasing waist size.

• 1:07:25Dr. Mark Hyman?

  Ah, so your belly fat. Yeah, that's a big one. Ways, okay. Is it ever too late to improve your brain health? And is, you know, can you really reverse loss? We talked about it, but what, is it too late? Is there a point at which it's too late?

• 1:07:39Speaker 00

  Well, I, there's certainly a point in which it's too late. I think end stage Alzheimer's is too late, but, uh, as we now see, interventional trials using lifestyle modification have proven effective even in individuals with established Alzheimer's disease.

• 1:07:55Dr. Mark Hyman?

  What's one food that you eat regularly for your brain?

• 1:07:58Speaker 00

  Salmon.

• 1:07:59Dr. Mark Hyman?

  Salmon. Okay. You're catching it up there in British Columbia right now.

• 1:08:02Speaker 00

  I caught one last night when the sun was probably young. Yeah, it was great. With, with an orca in the background.

• 1:08:09Dr. Mark Hyman?

  I love that. How about what's food, food you avoid?

• 1:08:12Speaker 00

  Fruit juice.

• 1:08:13Dr. Mark Hyman?

  Fruit juice. Yeah. No fruit juice. Orange juice is not a health food. And what is one supplement with the strongest evidence that you would take for your brain health?

• 1:08:22Speaker 00

  Vitamin D.

• 1:08:23Dr. Mark Hyman?

  How about GLP-1 drugs? Are they going to be brain health drugs?

• 1:08:26Speaker 00

  My sense is quite likely. I think there is some refinement that's obviously needed. We've seen an incredible interventional trial published in New England Journal of Medicine where Parkinson's was stabilized. I think GLP-1s have a future in brain health, uh, the brain health arena.

• 1:08:41Dr. Mark Hyman?

  Interesting. So it's an evolving story. We'll pay attention. Okay. What's more important for your brain, doing brain games or staying socially connected and intellectually engaged?

• 1:08:50Speaker 00

  I would say socially connected for sure.

• 1:08:52Dr. Mark Hyman?

  And if you're a 40-year-old right now, what are three numbers you want to know that reflect what's happening in your brain?

• 1:08:57Speaker 00

  You need to know your fasting insulin level, uh, your fasting, your fasting blood sugar, and I would say your waist to hip ratio.

• 1:09:05Dr. Mark Hyman?

  Those are good. It's all metabolic health. Okay. Now lastly, finish this sentence, the best way to stay mentally sharp for the next 20 years is?

• 1:09:13Speaker 00

  To change your thinking today, uh, to the extent that you realize that you are in, in control of your brain's destiny.

• 1:09:22Dr. Mark Hyman?

  You are in control of your brain's destiny. That is a, that is a big one. I think people all understand this about their heart or their weight, but they don't understand that their brain health is in their control. And I think that's what so much of your work has been highlighting for the last 40 years. This last book, Brain Defenders, Harness the Power of Your Immune Cells to Protect Your Brain for Life is amazing. It's out now. You can check out David's website, drpromanner.com. He's got a podcast and you'll learn all about his amazing work. Uh, he's definitely one of my mentors and one of my close friends. I'm happy to be in this world with him because without him, I would be much less smart. So thank you, David.

• 1:09:58Speaker 00

  I love you, brother.

• 1:09:59Dr. Mark Hyman?

  I love you too.

• 1:10:00Speaker 00

  Love all that you do. Good to see you.

• 1:10:03Dr. Mark Hyman?

  All right, buddy. Thanks so much. Enjoy salmon fishing in British Columbia. 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.

• 1:10:45Dr. Mark Hyman?

  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 that it does not constitute medical 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 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.

• 1:11:30Dr. Mark Hyman?

  When it comes to supplements, you only want the best for your body, the kind with the highest quality, cleanest, and most potent ingredients you can get. That's exactly what you'll find at my supplement store, where I've hand-selected each and every product to meet the most rigorous standards for safety, purity, and effectiveness. These are the only supplements I recommend to my patients, and they're also what I use myself. Whether you want to optimize longevity or reduce your disease risk, or you're looking to improve your sleep, blood sugar, metabolism, gut health, you name it, drhyman.com has the world's best selection of top-quality, premium supplements, all backed by science and expertly vetted by me, Dr. Mark Hyman. So check out drhyman.com because when it comes to your health, nothing less than the very best will do. That's drhyman.com, D R H Y M A N dot com.