How to Change Your Brain's Destiny Before It's Too Late | Dr. David Perlmutter – EP 809

In this episode of Passion Struck, John R. Miles sits down with neurologist and bestselling author Dr. David Perlmutter to reveal how the brain’s immune system responds to our everyday choices—and what we can do now to protect our brain health for life.

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

• 0:01John R. Miles?

  Hey friends, what if your biggest problem isn't that you're not doing enough, but that you've spent too long proving that you are enough? You can be successful, needed, and surrounded by people and still feel completely unseen. That's the problem I explore in my new book, The Mattering Effect. I show you how we become hyper-visible for what we produce, while quietly becoming invisible to ourselves, and introduce the matter framework to help you reclaim meaning, autonomy, trust, time, energy, and reciprocity. Stop auditioning for your worth, start living from it. The Mattering Effect is available for preorder now at matteringeffect.com. What if the cells designed to protect your brain can actually become the ones that damage it? When Dr. David Perlmutter joined me on Passion Struck,

• 0:47John R. Miles?

  he explained how the brain's own immune system can shift from protecting your neurons to damaging them, and why the choices you make every day may influence which direction they take. Take a listen to this.

• 1:01Speaker 01

  We're going to call those the microglial cells, and they are very sensitive to metabolism. When our metabolism is doing what it should do, keeping our blood sugar in check, our weight in check, our blood pressure where it needs to be, reducing inflammation, then these brain immune cells are supportive. They're nurturing our synapses, they're nurturing the blood-brain barrier, they're doing their best to keep our neurons functional and firing appropriately. But they can shift on us, they can turn their backs and become what I call in the book, the evil twin, same cell. It can shift when they are challenged by inflammation or metabolism issues in the body, and now they are destructive.

• 1:43John R. Miles?

  It's your friend John, and welcome to Passion Struck. I'm so glad you're here. Whether you're a longtime listener or someone who just discovered the show, thank you for pressing play today. Maybe you've built the life you were supposed to want, but you've quietly wondered why it still doesn't feel like enough. If that's you, you're in the right place. Every week, I sit down with the world's top scientists, researchers, and thinkers to uncover what it actually takes to build an intentional life that matters. Thanks for joining me, let's get into it.

• 2:23John R. Miles?

  Welcome back to episode 809 of Passion Struck. We're continuing our series, The Adaptive Brain: How Your Mind Learns, Changes, and Heals. So far, we've been exploring all the different forces that shape who we become. But today's conversation takes us somewhere we haven't gone yet, inside the biology of the brain itself. Because here's something I didn't fully appreciate before this conversation. Our brains aren't just responding to our thoughts and experiences, they're responding to the physical environment we create for them every single day. What we eat, how much we sleep, how much we move, our metabolism, our inflammation, even the health of our mouth and our gut

• 3:07John R. Miles?

  can send signals that influence what's happening inside the brain. And the center of this story are cells most of us have probably never heard of, microglia, the brain's immune cells. Joining me today is Dr. David Perlmutter, a board-certified neurologist, New York Times number one bestselling author, and longtime advocate for understanding the connection between lifestyle, metabolism, and brain health. His new book, Brain Defenders, brings decades of research together around a fascinating idea that the brain's immune system may be one of the key mechanisms determining whether our brains remain healthy or move toward decline. And what I found especially interesting

• 3:51John R. Miles?

  is that David doesn't frame this as something that only matters when we're older or already experiencing cognitive problems. He argues that the trajectory of brain health begins much earlier with the metabolic and lifestyle choices we're making decades before symptoms ever appear. And he believes we have more influence over that trajectory than we often realize. That makes this conversation so much more than dementia or Parkinson's. It's about agency. It's about understanding that the brain we're going to have years from now is being shaped by the environment we're creating for it today. So let's dive in. Here's my conversation with Dr. David Perlmutter.

• 4:33John R. Miles?

  Thank you for choosing Passion Struck and choosing me to be your host and guide on your journey to creating an intentional life that matters. Now, let that journey begin.

• 4:47John R. Miles?

  I am so honored today to welcome Dr. David Perlmutter to Passion Struck. David, it's so great to meet you.

• 4:54Speaker 01

  John, good to see you face to face, my pleasure.

• 4:58John R. Miles?

  I have been studying your work for years. And David, you've spent your career challenging wisdom in a lot of ways, from Grain Brain to Brain Maker to Drop Acid. But reading your brand-new book, which I have right here, Brain Defenders, I had the sense that this isn't simply your next book. It feels like it's a culmination of decades of research and clinical practice. And did writing this book change the way you personally thought about brain disease? Or did it finally give you a scientific framework to explain what you've believed for years?

• 5:35Speaker 01

  I think it did both. And it was the process of writing this book that really made me realize what you just said, John, and that is, over decades, where we focused on things like the damaging effects to the brain of a high carbohydrate diet, for example. We talked about that in Grain Brain. Back then, we didn't have the term ultra-processed foods. We just called them highly-processed carbohydrates. The role of the gut bacteria, the microbiome, in terms of brain health. More recently, looking at uric acid, looking at relationships, how they affect the brain. All of this information converged to create this book because, as it happens, everything converges on the brain's immune system

• 6:17Speaker 01

  that is the final arbiter of whether the brain's going to be healthy or not. I didn't know years ago that would happen. And it's very validating that we now have this fundamental overriding mechanism that explains all the inputs. And I think for what we're going to talk about today also explains why there's benefit to so many of the good things that we choose to do in terms of helping us chart a better brain destiny, in terms of things that influence our metabolism, our level of exercise, the foods we eat, the sleep we get, the relationships we have. All of this converges and influences the immune system. And that's the whole ball of wax as it relates to what's going to happen to your brain in the future.

• 7:03John R. Miles?

  I have really been interested in the topic of dementia for well over a decade now because for me, I saw my grandfather suffer from dementia, and it was really painful to see. His occurred because he had heart blockage, and he experienced a series of mini-strokes that ended up causing him to have oxygen loss to the brain, which resulted in him experiencing dementia. But here you have this gentleman who was just brilliant. He was an airplane pilot, ended up running all R&D for Kraft Foods, and just had this brilliant mind. And I remember towards the end of his life,

• 7:46John R. Miles?

  he could remember things from his early childhood, but really couldn't remember anything within five minutes of you talking to him. And as I first studied it, it seemed what a lot of the research was looking at was the damage after it's already occurred. And it seems like what your book is really talking about is the preventative behavioral aspects that we can deal with long before we ever experience where he had ended up. Is that a good way to think about it?

• 8:18Speaker 01

  John, you said something very important just now, and I want to reiterate it. You said, one of the sentences was, "He developed dementia because..." You're talking about your grandfather. And that's a question that we never ask. What do you mean? Why did somebody develop dementia? In your grandfather's case, he had a lot of vascular disease, okay. There's always vascular disease in the Alzheimer's brain as well. But I think we need to take that step, important step back, and ask, what is the because? And we know the causes of Alzheimer's, and it's not primarily genetic. And the important thing about understanding the causes of Alzheimer's is twofold. Number one, it lets us leverage that understanding so we can be preventive, as you described.

• 9:01Speaker 01

  And second, it really lets us understand what we can do to be therapeutic even today, once a patient has this situation already established. We're talking about 7.6 million Americans now having been given that diagnosis. And I fully understand what you went through with your grandfather. I went through that with my own father, a brilliant brain surgeon, and watched this happen to him, and it's devastating. So that's really what this is about. We live in a world where we are convinced to live our lives however we choose, and that there's a wonderful drug or suite of drugs available to fix our maladies, whatever they may be. The reality is, we don't have any meaningful treatment for Alzheimer's disease,

• 9:45Speaker 01

  John, as you and I have this conversation. That is, in the face of the fact that there are FDA-approved Alzheimer's treatment, but I just said that we don't have any meaningful disease, treatment, as it were. That is really reiterated by a recent study called a Cochrane Analysis, looking at the FDA-approved Alzheimer's drugs, which target a protein in the brain called beta amyloid. We've been given this story that the cause of Alzheimer's is the accumulation of beta amyloid in the brain.

• 10:21Speaker 01

  If that were the case, then getting rid of the amyloid should be problem solved. It turns out it is not the case. This Cochrane analysis looked at 17 different studies, 20,342 individuals involved in the studies, over 18 months, and found that, number one, the drugs were virtually ineffective at all in terms of slowing the downward progression of this disease. And number two, about one in four individuals suffers either a bleed into their brain and/or a brain swelling, or even death. So in terms of looking at risk and benefit ratio, these drugs categorically fail. And yet, what did you just talk about? The idea of preventing the disease in the first place?

• 11:04Speaker 01

  We absolutely understand the inroads to Alzheimer's disease, and it's all about our body's metabolism. It's about our blood pressure, our blood sugar, insulin functionality, and inflammation. All of those issues converge on what this book is about. Getting back to your original topic, they all converge on regulating the brain's immune system. We're going to call those the microglial cells. And they are very sensitive to metabolism. When our metabolism is doing what it should do, keeping our blood sugar in check, our weight in check, our blood pressure where it needs to be, reducing inflammation, then these brain immune cells are supportive.

• 11:47Speaker 01

  They're nurturing our synapses, they're nurturing the blood-brain barrier, they're doing their best to keep our neurons functional and firing appropriately. But they can shift on us. They can turn their backs and become what I call in the book, the evil twin. Same cell. It can shift when they are challenged by inflammation or metabolism issues in the body, and now they are destructive. This is the fundamental underpinning, not just of Alzheimer's, but all neurodegenerative conditions are united by this upstream mechanism, which is a shift of the brain's immune cells, what I call the brain defenders, to being brain destroyers. That's the fundamental of this book, and that is the fundamental principle that underlies

• 12:32Speaker 01

  virtually all neurodegenerative conditions, really including other things like long COVID, PTSD, major depressive disorder, and of course, Alzheimer's, Parkinson's, MS, PSP, multi-system atrophy. These are all united by this one shared mechanism. So, understanding the brain's immune system, the pivotal role that it plays in determining your brain's destiny, and perhaps most important for our time together today, what we can do to keep those cells on our side, supportive, brain defenders, is really what this is all about.

• 13:07John R. Miles?

  David, can I just take one step back? Because I'm guessing 90% of my audience has never heard of microglia before. What are these cells that you just mentioned? And why have they become so central to everything that you just described?

• 13:25Speaker 01

  It is absolutely emergent science. It is absolutely cutting edge. But I will tell you, the focus on the microglial cells, the brain's innate immune cells, is vast at this time. It is at the forefront of all of the highly regarded neurology literature. Every month when a new journal comes out, it's really what is being featured. And so, these are the brain's immune cells. They make up about 10% of the cells in your brain. People are surprised that, they think your brain is packed full of neurons, end of story. Well, the reality is, there are a bunch of different types of cells in your brain. There are supportive cells that help brain be connected via its structure and its function

• 14:10Speaker 01

  as well. The microglia, the brain's immune cells, when we say immune cells, people are thinking, well, these are the cells that might go into action when there's an infection, or trauma, or a stroke, or something. That's when the immune system gets activated. But they do a heckuva lot more than that. They are involved in nurturing the brain and keeping our neurons functioning, in nurturing the synapses, where one brain cell connects to the next. And so, it's a broader interpretation and understanding of immunity as it relates to the brain. And what is so fundamentally important is that what shifts these brain cells to become destroyers of the brain, again, a fundamental mechanism involved across the spectrum of

• 14:55Speaker 01

  neurodegenerative conditions, is a change in their metabolism. And the take-home message is that the metabolism of these cells mirrors your body metabolism, your blood sugar, your insulin functionality, your level of inflammation, your body weight, your blood pressure. All of these issues influence whether those microglial cells, those brain immune cells, are going to allow you to have a highly functional brain for the rest of your life, or they will pave the way for brain decline, which is so incredibly common in the Western world.

• 15:31John R. Miles?

  What is actually happening? I know the cells are constantly deciding whether to repair tissue or to mount an immune response, but what are they actually sensing inside the brain every day which causes those two responses to happen?

• 15:48Speaker 01

  They sense a lot of different things, which is really so interesting. They're just in surveillance mode constantly. If they see, for example, a breakdown of a bacterial product, a protein from a bacterium, or the DNA from a bacterium, that'll set them off. That'll send them to being what we call the M1 threatening configuration. If they see inflammation that comes from anywhere in the body, like even from the gut, that'll trip them into being brain destroyers. If they see excessive free radicals, if they see oxytocin, for example, the love chemical, the love hormone, that will tend to shift them back to being nurturing, brain supportive. So they're constantly being targeted by various types of stimuli.

• 16:33Speaker 01

  Excessive blood sugar will set them off. Changes to proteins brought on by excess blood sugar will set them off. So they're constantly in receptor mode, where they're looking at the environment, and that environment determines whether they're going to be supportive or destructive. And really, what's, I think, fascinating and empowering is that we can control that environment. I mentioned, for example, bacteria and the breakdown products of bacteria. We're at a new stage of our understanding of the brain's microbiome. Did you hear what I just said? Everybody's heard of the gut microbiome. The brain has its own microbiome. It has bacteria or components of bacteria.

• 17:16Speaker 01

  It has viruses that live within it, so it's not sterile. And certain bacteria can actually target these microglial cells and cause them to stop being supportive and become destructive. Let me give you an example. There's a mouth bacterium that lives in the gums called, crazy name, Porphyronis gingivalis. It turns out that with poor dentition, poor periodontal health, that bacterium can make its way to the brain and can immediately set off inflammation and trigger these microglial cells into their destructive mode. So, that is a simple argument in favor of having better oral care. Flossing, we don't like to floss, but we should floss.

• 18:01Speaker 01

  Brush our teeth a couple of times a day. Use a water flosser. Get our teeth cleaned professionally every six months. These are important things to do to keep periodontal disease at bay, because we know there's a very powerful association between periodontal disease and risk for Alzheimer's. The mouth-brain connection. Who knew, right? We've heard of the gut-brain connection, it's almost cliche at this point, but the mouth-brain connection. And as we learned from a publication yesterday, hot off the press, a liver-brain connection, that the liver secretes various types of chemicals that can either be supportive or destructive for the brain. Why is exercise associated with a dramatic risk reduction for the development of Alzheimer's?

• 18:45Speaker 01

  Because there's a muscle-brain connection. When we exercise, our muscles create chemicals called myokines, myo meaning muscle, kinds means they move around, they go to the brain, they do good things, they target metabolism. And as we now know, when the brain metabolism is improved, our brain immune cells, these microglial cells, are on our side. They're loving, they're nurturing, and they're keeping our brains away from becoming degenerative organs, keeping us at a lower risk for brain degenerative disorders. What I'm saying is, very much, we are the architects of our brain's destiny, based upon our lifestyle choices that we make every single day.

• 19:26John R. Miles?

  We'll be right back with more of my conversation with Dr. David Perlmutter. As you're listening today, I'd like you to think about one question. What kind of environment are you creating for your brain? One of the ideas I found most compelling in this conversation is that we often think about brain health as something that happens to us. But David offers a very different perspective. He argues that our brains are constantly responding to the signals we give them through our metabolism, our sleep, our movement, our food, and the way we live. That idea connects with something I've been exploring in my upcoming book, The Mattering Effect, coming this October. Because just as our physical environments shape the brain, our social environments shape us too.

• 20:10John R. Miles?

  The people we spend time with, the cultures we're a part of, and the messages we receive about our worth can influence how we think, feel, and behave. The larger lesson is one we've been returning to throughout this series. We're not passive observers of the life we're living, we are constantly creating the conditions that shape what comes next. If you'd like to go deeper into today's conversation and pick up the companion workbook, you can find them in theignitedlife.net on Substack. It's designed to help you take what you're learning here and turn it into practical changes in your own life. You'll find links to my book, David's book, and The Ignited Life in the show notes. Now, a quick break for today's sponsor. Thank you for supporting those who support the show.

• 20:58John R. Miles?

  You're listening to Passion Struck on the Passion Struck Network. Now, let's get back to my conversation with Dr. David Perlmutter. David, I'm going to shift the whole interview because I was going to go through a lot more of the backstory, and I think you're right. I think we need to talk more about the discoveries here. What does this mean for us in our everyday lives? I just, for your own background, am someone who has unfortunately experienced a number of traumatic brain injuries, some sports-related, some combat-related, some childhood injury-related. But as a result of that, I have really been trying to study my brain health for a number of years. And

• 21:41John R. Miles?

  one of the most important things I discovered when I was originally thinking I needed to focus on amyloid plaque was sleep, trying to clear that plaque out. But sleep benefits us regardless if we're doing it for that purpose or for the purpose that we're discussing right here. What actually happens to these cells we've been discussing while we're sleeping? And how quickly does poor sleep begin changing brain inflammation?

• 22:10Speaker 01

  I'm going to answer the second question first. How quickly does poor sleep affect inflammation? One night. Wow. It's that dramatic. We see significant increase in markers of inflammation in the body, increase in blood sugar, reduction in insulin functionality after one night of non-restorative sleep. That has behavioral implications in terms of our ability to make good decisions the following day. Wrote a book about that called Brainwash. But it happens that quickly. So, brain is fundamentally important for the microglia to be functional and stay on track in terms of doing good things for the brain.

• 22:49Speaker 01

  Now, let me go back to the brain trauma issue because it's a very big inroad to activating the brain's immune system. When we experience a brain injury, this activates the microglial cells. That's actually a good thing because these things go about helping to clean up the debris and re-establishing health. The problem becomes when these cells remain in their activated form for longer than they should. They should revert back to being healing cells. They should revert back to building better synapses, nurturing the neurons, and repairing the blood-brain barrier. But they often do not when they are challenged

• 23:30Speaker 01

  by other things like what? Like metabolic challenges. For example, in large studies of a brain injury, the risk of a poor outcome is dramatically increased if you happen to have been a type 2 diabetic at the time of the injury. Your hospitalization will be longer and your degree of impairment will be greater if you're a diabetic across all levels of injury in comparison to not being diabetic. Why? Type 2 diabetes is a profound metabolic challenge to the brain's microglial cells. They don't shift back as readily to

• 24:10Speaker 01

  being in their healing environment. So, the main task in terms of recovering from a head injury is shifting those microglial cells back to being supportive as opposed to being destructive. Their function, whether they're supportive or destructive, depends on their metabolism, how their mitochondria are working, for example. It's why things that target the mitochondria, like hyperbaric oxygen, for example, are so effective in treating brain injuries, treating head injuries. It's why when an individual has a brain injury, we want to use the ketogenic diet, for example, because that brings the brain's metabolism and the metabolism of these brain immune cells back online. It's why with a head injury,

• 24:55Speaker 01

  we want to control blood sugar as best we can. It's why we want to reduce other sources of inflammation as best we can. Who knew that in a head injury patient, it was important to target the gut-brain connection, to evaluate the function of the microbiome in the gut to help reduce inflammation, to set the stage for better outcome, better recovery. We certainly know that we've been doing that in individuals with long COVID. It's an exactly similar scenario. We want to do everything we can to improve metabolism of the microglial cells so they will revert back to being brain supporters, or what I call in the book, "brain defenders."

• 25:40John R. Miles?

  Just a follow-up question on traumatic brain injuries. I know as I was going through my treatment for this, given that a number of these happened in combat situations, the doctors had a very difficult time trying to determine, was it PTSD that was causing the long onset of symptoms that I had, or was it strictly related to brain trauma itself? Why do those two conditions overlap so much? And does what we're talking about here play into it at all?

• 26:16Speaker 01

  The answer is 100%. When we examine patients with a variety of disorders using a very sophisticated type of research tool called a TPSO PET scan, this is a scan that is able to determine the level of activation of these microglial cells, these brain immune cells. When they're active and being destructive, the TSPO scan lights up. So, the TSPO scan is positive, as you would expect, in Alzheimer's, in Parkinson's, in MS, but it's also very positive in PTSD and also in head trauma and even in long COVID. So, the point is

• 26:58Speaker 01

  that these are issues in which there is this fundamental shared mechanism, that once these microglial cells become activated, we have a variety of manifestations, things like PTSD, major depressive disorder, and frankly, even increased risk for Alzheimer's and even Parkinson's. One would wonder, for example, why head trauma would put you at risk for Parkinson's? What could your relationship possibly be? Well, look at Muhammad Ali. That's called pugilistic. That means a boxer. Of Parkinson's, when you activate those microglial cells, it can have a variety of manifestations. In Parkinson's, a motor

• 27:37Speaker 01

  manifestation. In PTSD, an emotional manifestation, a psychiatric manifestation, a mood disorder, major depressive disorder, and even Alzheimer's. As you had mentioned briefly, that you were concerned about, now that you'd had multiple experiences of head trauma, you were concerned about beta amyloid. Obviously, you were thinking about the fact that you were at risk for, increased risk for developing Alzheimer's disease by virtue of your head trauma. That's well documented, not anything you're the only one who thought about. Why does it happen? It happens because of activation of the microglial cells. So, your original question to me is, why this book? Why now? Because it unites all of these seemingly disparate

• 28:22Speaker 01

  issues that we've pondered for so many years to a fundamental understanding that what's going on in Alzheimer's, in PTSD, what's brought on by head trauma, what causes Parkinson's, fundamentally, is this activation of the brain's immune cells away from being supportive to being destructive. It opens up a lot of potential, I think, to throw a very wide net in terms of paving the way for better brain health moving forward.

• 28:53John R. Miles?

  David, I remember having a conversation with my grandparents. They had been smokers, like many people of their generation had been for many years, probably a decade plus. And then, the surgeon general's warning came down on the impacts that cigarette smoke could have on each of them, and they both pretty much quit cold turkey overnight, never smoked again. Where I'm going with this is, a number of years ago, I started to do more and more research on alcohol, and I started to realize that alcohol was having a profound impact as well, and it's getting more and more documented. But one of the biggest areas

• 29:34John R. Miles?

  I was concerned about was the impact that it was having on my sleep because it was causing me, I'd go to sleep, and I was using it to help me with my PTSD, but what would end up happening is, 2, 3 o'clock in the morning, I'd wake up completely awake, and so it was having a negative impact, not only on that, but on other areas of my life. So, I have been alcohol-free now for over three years, and I was talking to Daniel Amen about this because it's like... I feel fully charged now, fully awake every day that I get up. It's so drastic a change in how I feel.

• 30:18John R. Miles?

  But alcohol is something you explore in the book as well, and maybe you can touch on it.

• 30:23Speaker 01

  Yeah, it's funny because I did an interview for Newsweek just yesterday. It actually came out yesterday morning. They said, what are the things that this neurologist, the six things that you would never do? And alcohol is one of those. Not that I wouldn't have a glass of wine from time to time, but alcohol is an issue at multiple levels. A, it is a direct neurotoxin. It is toxic to neurons. No matter how you slice it, i.e., whether it's Scotch or red wine. We used to say, well, the epidemiology studies demonstrated that one glass of red wine for women, two glasses per day, actually was associated with a reduced risk for Alzheimer's disease. I think that's been reassessed and has been demonstrated to be really, no pun intended, self-serving.

• 31:07Speaker 01

  The reality is that no alcohol is the best choice that you can make. The direct effects of alcohol being a toxin, number two, as you've characterized, the effects of alcohol on sleep are significant. We talked about why that is so important from an inflammation perspective, from a metabolism perspective. And number three, alcohol has bad effects on the gut microbiome. That increases inflammation in the body, which these cells in the brain, the microglial cells, respond to. So Dan Aman, I've had many a dinner with Dan Aman, and he is correct that the best choice is none as it relates to alcohol. And if somebody does have a drink once in a while, I think that's not a huge issue.

• 31:49Speaker 01

  But the idea of consuming alcohol on a daily basis, I think, is a clear and present danger as it relates to brain health and is one of the fundamentals here. I think that ultra-processed foods represent a dramatic risk to brain health, as does what we call sedentarity, being sedentary, not moving around. These are huge issues. We talked about sleep, and we need to talk about diet, but these are the pillars of brain health. And we live in a world, I think, John, that really wants us to believe the messaging that we can do anything we want with our lives. Drink whatever you want, don't exercise, eat the stuff that is advertised. And when we're suddenly having some cognitive issues, which is late in the game,

• 32:33Speaker 01

  well, there'll be a wonder drug for you. That drug doesn't exist. We do not have any meaningful pharmaceutical treatment for Alzheimer's disease as you and I had this conversation at this time. And again, this Cochrane analysis that came out this year, looking at the effectiveness of the drugs that target exactly what you mentioned earlier, beta amyloid, found that the drugs that are FDA-approved to reduce beta amyloid in the brain absolutely reduce beta amyloid in the brain. No doubt about it, they're monoclonal antibodies, but do they have any significant effect on the downward course of Alzheimer's? They do not. This is the gold standard approach to studying. A question in this case, the question is, do the drugs work for Alzheimer's?

• 33:19Speaker 01

  They evaluated 17 different studies, 20,342 individuals. They found that the drugs don't work and that they are significantly dangerous as it relates to brain bleeding and brain swelling. So what are we left to do? Well, I think, as we've talked about already, we are in a situation where we know we can prevent this disease significantly. And even more importantly, we now see interventional trials, meaning treating Alzheimer's patients with lifestyle intervention that targets the brain's immune system and having results that are unparalleled. There's certainly no drug that even comes close. May I quote one study for you?

• 34:03Speaker 01

  Done by researchers Rudolph Tanzi and Dean Ornish at Harvard. A study, only 51 patients, small study, I agree. But these are patients with Alzheimer's disease, underwent a 20-week program. What did the program involve? We're going to change your diet, we're going to get you to exercise, and we're going to reduce the stress in your daily life. And what did they find? These are patients in 20 weeks' time that would have otherwise continued to decline. That's what is expected once the diagnosis of Alzheimer's is made. 70% of these patients either stabilized or had improvement in their cognitive function.

• 34:45Speaker 01

  And this was not a drug, and it is not patentable, and it doesn't require FDA approval. Think about that. This isn't something you'll hear about on TV as an advertisement for a product that somebody can own. So how these lifestyle interventions work is because they change the function of these immune cells. Getting back to our original question during this interview, what is the big deal? And the big deal is that these are the keys to the kingdom, and it's under our control, which is so very exciting.

• 35:20John R. Miles?

  David, I want to make this real for a listener. So I thought I would just do a hypothetical. Let's imagine we have someone listening to us today. They're 40 years old, they're busy, they have kids of different ages, they're sleeping poorly, they're eating too much ultra-processed food, they're stressed out, their work is, and family obligations are prohibiting them from exercising as much as they need to. And they're hearing you and I talk. Where would you suggest they start? Not with trying to overhaul everything, but with one thing.

• 36:03Speaker 01

  I think the one thing, the place to start would be to embrace the understanding

• 36:11Speaker 01

  that you are controlling your brain's destiny. That's step one, because if you don't get that step, nothing else will follow, right? And you bring up an incredibly valuable point, and that is that Alzheimer's, the cognitive dysfunction that people begin to experience in their mid-60s and 70s begins in the 30s and 40s. Because that's when the metabolic issues that you just wonderfully described begin to take root and begin to affect these cells in the brain that are going to either support a wonderfully functional brain or pave the way for the brain to decline. It's in our 30s and 40s that these metabolic issues begin to challenge what we call the microglial cells.

• 36:55Speaker 01

  So that's who needs to be listening. Because frankly, when individuals have already been experiencing cognitive issues and become forgetful of Wi-Fi codes, grandchildren's names, phone numbers, et cetera, we're well down the continuum. And I prefer not to use that term continuum. Continue means it's going to continue. Let's just get, abandon that term, mea culpa. I'd say that the fundamental take-home message is to really clean up your metabolic house and in your 30s and 40s, in your 20s, in your teens, when you're a newborn, perhaps even in utero. When does it begin? We know that inflammation is increased in children born by C-section,

• 37:39Speaker 01

  as is autoimmunity, in comparison to children born, newborns by vaginal delivery. So when does it begin? But again, I would say that, yes, you are on target, targeting the 30 and 40 and 50-year-olds. When we look at the overall health of that segment of the population here in America, it's very worrisome. We know that in American adults, that 60% of calories are derived from ultra-processed foods, dramatically associated with increased Alzheimer's risk by virtue of the effects of these foods on blood sugar, insulin functionality, and inflammation. So it's changes that have to happen.

• 38:22Speaker 01

  So I think, though, to be fair to you, what was that one hook? And to get this person on the road to a better lifetime brain experience? And I'm going to answer it in a bit of a cagey way, because I was asked this question in a couple of books ago. And what, and I, to me, it is whatever on-ramp works for that person. Because whatever that on-ramp is, will pave the way for the others to follow. Just the fact that I've started exercising, no. Just the fact that I've changed my diet, no. Just the fact that I'm paying strict attention to getting a good night's sleep. Whatever it may be, will then set the stage for wanting to do the rest of the program.

• 39:08John R. Miles?

  I think it's the same way you approach any life change. I often tell people that I often think about life as on five, you're sitting on a bunch of stools. What's on those stools could be whatever priorities you want to put on them. For me, I put my emotional health, my physical health, my mental health, et cetera, my relationship health, et cetera. But typically, for most people, some of those pillars are strong and some of those pillars are weak. So you basically have to look at your pillars and pick one to start working on. And then what I have found, and in my own life, and what ends up happening to everyone is, once you pick one and start working on it, you naturally gravitate to the other pillars.

• 39:52Speaker 01

  Exactly. I just need one on road.

• 39:55John R. Miles?

  Exactly.

• 39:57Speaker 01

  But interestingly, you didn't mention cognitive health. You said emotional health, spiritual health, physical health. But like many, people don't think that they can influence their cognitive health. You've talked to Dan Aman, you know, that's just not true, that our choices are fundamental as it relates to cognitive health. Risk of being demented in America at age 65 is one in nine. That's 11% of people 65 or older is demented. That is sobering. And getting back to when do we begin the program? John Kennedy said that the time to fix the roof is when the sun is shining. And that's why I'm grateful to

• 40:40Speaker 01

  have this time with you today, because I want this message to get out. You went through it with your grandfather. I went through it with my father, and it's awful. And I don't want to put my kids through that. And again, for the Alzheimer's patient, ultimately, they transition to a point where they don't really understand what's going on. It's the loved ones that are so impacted by it. And we can do better. This is an emotional issue. It's a financial issue. We're spending $360 billion in America today to care for Alzheimer's patients. And when you look at that number, and you look at, there was a recent Lancet report in 2024, that said, if we could look at 14 different lifestyle variables and address

• 41:24Speaker 01

  them, that the number of Alzheimer's patients would be reduced by 50%. My mission would be, I'd be happy at 10%. I'd be happy at 1%. If 1% of people won't have to go through what I went through, in terms of being a family member, loved one, to me, that's a good day's work. I certainly want to go for higher than that. But it's just, it's so black and white clear, that the brain is fully responsive to the choices we make each and every day. And John, I get what you're saying, that these are busy people, and they have kids at home, and soccer practice, and I got home at 6 o'clock, I'm late, and I

• 42:08Speaker 01

  eat something on the run. Start somewhere. Train for an event. Pay attention to your sleep. Cut back on the packaged foods. Do your best to exercise. Even weekend warriors derive significant benefit from exercising even two days a week. So there are opportunities. I want exercise to go, not from finding the time, but to making the time.

• 42:31John R. Miles?

  David, if the evidence is so compelling, and so many new articles are coming out every single week, why hasn't it changed clinical practice yet?

• 42:41Speaker 01

  It has, but not to any significant degree. And I think that it's very difficult to morph the standard of clinical practice in America, and really in Western countries, away from the 15-minute interaction and a prescription being written, and then move on to the next patient. That's the most efficient way of having a high put-through in your practice, knowing that you've then got to do all the charting and all the bookkeeping later in the day. The prescription pad is the coin of medical commerce. And that's the way it's done, to spend the hours that it takes in giving people this information, which is far more important and far more valuable, in my opinion, is not remunerative.

• 43:25Speaker 01

  It is not remunerative as it relates to pharmaceutical remuneration, and is difficult. And to be fair, most medical doctors do not have much training as it relates to lifestyle interventions. I, for one, had zero training during my medical education as related to nutrition. Not one hour. You do, if you're a chiropractor, you get a lot of nutritional training, and I think that's so valuable. If you go to veterinary school, a veterinary school, you get a ton of information about what people should be feeding to their cats and dogs, whatever type of vet you become. I tell the story of, many years ago, our

• 44:05Speaker 01

  dog was losing its fur. We took Tico, our dog, to the vet, my wife and I. And the first question she asked us was, what are you feeding Tico? And I was stunned. I thought, why do I never ask that question to my patients in my office? Because people would look at me funny, right? Why would you be asking what I ate? I'm here to take care of my headaches. Well, your headaches may be from the foods that you're eating. Who knew? So it is, medical practice is a situation of old habits dying hard.

• 44:35John R. Miles?

  As I'm hearing you talk more and more, what I'm hearing is, the headline really isn't about sleep, or food, or alcohol, or exercise itself. The headline is really that our brains are constantly responding to the environments we create for them.

• 44:53Speaker 01

  Absolutely.

• 44:54John R. Miles?

  So that's the right way to think about it?

• 44:57Speaker 01

  That's right. And you'll see articles about sleep, and separate articles about exercise, about various supplements. Vitamin D's been in the news this past couple of weeks for good reasons. And I think articles are written about these unique hacks, I hate to use that term, but things in particular that you can do. And the mission of this book is to present as many of them as I could, in the most understandable presentation I could muster, such that people can do as many of them as they feel comfortable. And I recognize that you can't do all of them. We can change the brain's trajectory. Each of us can do that. We have the tools. It's a question, as you, I think, characterized

• 45:36Speaker 01

  earlier, of implementation. But I think that the idea of implementation becomes more powerful and more meaningful when you understand the scientific underpinning for why it is that I'm going to increase my exercise, or I'm going to not be drinking cola and fruit juice. Why? Because of the sugar content, and how that's threatening the brain's immune cells, and how research has demonstrated, yes, that consumption of fruit juice, we've all been told, drink a glass of OJ or apple juice each day. But those who drink have higher levels of fruit juice consumption, have a higher risk of developing Alzheimer's disease, significantly higher, and stroke for that matter.

• 46:18John R. Miles?

  David, I always like to turn this around. You've been talking a lot to the audience about the changes that they could do in their life. How has that research that you've been talking about throughout the interview changed what you're doing in your own life?

• 46:35Speaker 01

  I think for me, what's been so powerful is the new knowledge that I have in terms of how each of these things that I have been doing for a long time, how it ultimately converges on the immune system. It encourages me, it also encourages me to keep an open mind about things, because new things are being presented each and every day. I have a Google search on certain things that allow me to be as up to date as a person could be with new announcements about new findings every single day. My program does change. It is absolutely flexible and open to new suggestion. I, many years ago, subscribed

• 47:16Speaker 01

  to a fully vegetarian diet. That has changed. I don't do that now, though my diet is plant forward, i.e. mostly plants, but I do eat animal products. So I think that's important. And I've been called out for that. And people say, well, Dr. Promoter, you told us several years ago, one thing, and now you're saying something a little bit different. And my hope is that people ultimately be at a place of understanding that when messaging changes, it changes because the scientific underpinning has changed. As you asked earlier, alcohol. I was of the camp that said, one glass of wine for women, two glasses of wine per day for men. That's what the science shows. Well, the science doesn't show that anymore. So

• 47:57Speaker 01

  I've changed that messaging. For me, the idea is that my program, my keep myself physically and cognitively intact, I think will keep changing as the science dictates.

• 48:08John R. Miles?

  One thing I did want to spend a little bit of time with you on is, I remember about 15 years ago, I went to my primary care provider and I told him that I was really big on taking supplements. And he looked at me and he said, John, you are completely wasting your money. The, the reason I was taking them is because of the inflammation that I had on my brain, I had researched things like magnesium and its importance to my sleep. I had researched omega threes and its importance in treating some of the inflammation that I had, along with

• 48:49John R. Miles?

  other things. And you spend an entire chapter on these supplements. For someone who's hearing what my doctor said to me as a starting point, why did you choose to devote a whole chapter on this?

• 49:02Speaker 01

  Well, what does the word mean supplement? Supplement means in addition to, and is there a requirement for having something in addition to the foods that you eat? And my answer is yes, there is. Why? Because our food quality isn't the way it used to be. And the level of confrontation of our bodies by our toxic environments needs higher levels of certain components to combat what we are now exposed to. And I don't mean to be disparaging towards your doctor 15 years ago, but one would wonder how much training she or he had as it relates to nutrition and the judicious use of supplements. The science that underpins the relationship, for example,

• 49:47Speaker 01

  of low vitamin D level to increased risk of Alzheimer's is sound. Most recently, as in about two weeks ago, a fascinating report was published demonstrating that low levels of vitamin D are associated with a significantly increased level of an Alzheimer's marker called P tau 217 we talk about in the book. We don't talk about this relationship because it wasn't even announced at that point. I didn't have that information. So, does that say to me that there's a place to take vitamin D? Yes, if you have a low vitamin D level. So, what you just heard me say is, I'm not making a blanket recommendation, everybody on the planet should

• 50:30Speaker 01

  take vitamin D. What I am saying, though, is that if your vitamin D level is less than it should be, then you need to get your vitamin D level up to an optimal level. And somebody telling you that you don't need supplements, that statement shouldn't be made until you check. What is your vitamin D level? What is your intracellular magnesium level? What is your homocysteine level? That's a marker of the functionality of B vitamins in your body. Higher levels of homocysteine are associated with Alzheimer's risk. My homocysteine levels were elevated because of a little bit of a genetic quirk that I happen to possess, as

• 51:09Speaker 01

  does about 25% of Americans. Therefore, I need more vitamin B complex of a special type called methylated B. I would never have known that if I didn't check my homocysteine level. My vitamin B12 level is where it needs to be for good brain function, based upon blood testing. So, I think that supplementation is very important. There are some supplements that are now a little bit edgy, but have been determined to be helpful with respect to the brain's immune cells. They are something called dihydromericetin and rosemary acid. Those are a little bit out there, but they hold great promise, in my opinion, to help, A, reduce

• 51:50Speaker 01

  inflammation, and B, help the shift of the immune, brain's immune cells away from being supportive to being destructive. We don't want that to happen. These supplements hold promise in that regard. And I will say, after that section in the book, we talk about future looking technology, even some really exciting things that are on the near term horizon that target the microglial cells that have already been demonstrated to be effective in Alzheimer's treatment with Alzheimer's human patients that are not drug related. So, what I'm seeing is a massive shift in the research, looking away from the beta amyloid hypothesis, it's

• 52:32Speaker 01

  only a hypothesis, towards the idea that these microglial cells hold great promise, with fascinating research being published now on a virtual daily basis, that is really going to set the stage for us to ultimately keep brains healthy and even treat this devastating condition.

• 52:52John R. Miles?

  And the book goes into a ton of different things, from wearables to different supplements that you should consider taking. What I ended up doing is I ended up firing that primary care physician, and I started to go, go see a DO who ran a whole battery of tests. I

• 53:12Speaker 01

  Home Run.

• 53:14John R. Miles?

  Yes, is a sponsor of mine. So, that's what I use now to help do these things. But it was the first time in my life that anyone had ever tested all these different levels on me.

• 53:26Speaker 01

  Otherwise, you're shooting in the dark. And I am, you have no idea what, how that makes me feel, that you had that shift. And you left that other doctor, I hope you do well. And now you're testing and then fixing what needs to be fixed to bring your levels up to optimal for total body health and yes, for brain health. The brain is very sensitive to lower levels of some of the things we've covered. Low magnesium, low levels of the omega threes, low vitamin D, not enough B vitamins as it relates to homocysteine, low levels of B12. We've known about that for decades. So, good on you. That is just what I'm looking for.

• 54:04John R. Miles?

  David, we've talked a lot about many different things today. The last thing I did want to ask you about is the GLP-1s and what your thought is about them and everything we've been discussing.

• 54:18Speaker 01

  Well, GLP-1s are the peptide de jure. Everyone wants to talk about peptides and feels that there's a place for peptides. And as it relates to GLP-1s, this is without question, the most powerful metabolic target regulator ever conceived. And I'm saying that in a positive way, but I'm going to need a moment to unpack all of this. So, the most powerful inroad to metabolic health, bar none, are these GLP-1 agonist drugs. So, in the consideration that these diseases we are talking about are metabolic at their root, therefore affecting the brain's immune system, which is very sensitive to metabolic issues,

• 55:03Speaker 01

  might there be a place for regulating these GLP-1s or using the GLP-1 drugs as it relates to the neurodegenerative conditions because of their effects on metabolism? The answer is, in my opinion, yes, there is. Let me give you an example. In 2024, in the New England Journal of Medicine was a study published using a GLP-1 agonist drug to treat patients with Parkinson's disease. There were 151 individuals randomized to either receive placebo or a GLP-1 agonist drug for a year. And they followed these individuals on a standard scale. What they found was really quite remarkable, that in the untreated group or the group receiving

• 55:47Speaker 01

  the placebo, they declined as one would expect in one year as a result of their Parkinson's. In the group receiving the GLP-1 drug, their Parkinson's disability did not decline, it actually stabilized and actually slightly, when you look at the graph closely and the numbers, improved. That is the first time in history that Parkinson's disease itself was actually targeted. Yes, we have drugs to treat the symptoms, the tremor, the rigidity. I've been using them for 40 years, right? And they work well. And there's no question, they're incredibly valuable, but we've never targeted the underlying fire. We've only

• 56:28Speaker 01

  treated the smoke. So, I think the GLP-1 drugs hold great promise. I will say, as it relates to the Parkinson's study, about 48% of those people had significant gastrointestinal side effects. So, more work needs to be done. I think there's great promise. As it relates to Alzheimer's, a recent trial called the Evoke and the Evoke Plus trial used an oral form of semaglutide. And it was a one-year study done at multiple institutions, involved 3,800 individuals, and they did not reach their endpoint. These are patients with Alzheimer's disease. There was no meaningful endpoint improvement in or stabilization of their

• 57:11Speaker 01

  cognitive function. However, a measurement of inflammation that you had when you had the function health test called C reactive protein, measures inflammation, was reduced by around 30%. That is important. It means that there is a signal here, and that maybe we need to do this over a longer period of time. Maybe we need to do a study that is using intravenous or injectable form of GLP-1 agonist drug that will cross the blood brain barrier, because remember, this was an oral form. But I want to look at any intervention in terms of risk benefit ratio. Certainly, the, the risk here is far less than the approved

• 57:56Speaker 01

  Alzheimer's drugs, but we don't see the benefit yet in terms of an oral form, but a dramatic benefit in terms of the injectable form, at least in Parkinson's. So, I think there's great promise there. It hasn't entered the mainstream toolbox as yet, but my mission is to embrace whatever's going to help people and not have a meaningful side effect profile. The face of Alzheimer's is a uniformly fatal disease. So, using a GLP-1 agonist drug, if it helps slow it down or even stabilizes it and proven to be effective, I would be in.

• 58:33John R. Miles?

  David, I highly recommend Brain Defenders: Harness the Power of Your Immune Cells to Protect Your Brain for Life. This episode will be coming out during its launch week, and I'm so glad this book is coming out in the world. You've got a great podcast, other awareness things that you're doing. Where's the best place for people to capture all that if they want to go there?

• 58:55Speaker 01

  I'll get there in a second, but let me just say thank you. I appreciate this opportunity. I'm happy the book is getting out to the world. 16 countries already are going to publish it, so it's a global problem. And as the Western lifestyle spreads around the world, we're seeing in tandem rates of Alzheimer's increasing as well. So I guess the best place to find me is drpearlmutter.com, D R Pearl Mutter dot com. The website for the book is there's all kinds of things that people get when they buy the book. The book is called Brain Defenders and the website is called braindefenders.com. So that's where people can get more information. But again, I appreciate your time today, John, and having me on the program.

• 59:35John R. Miles?

  It was my honor. I've wanted to have you on for so long, so I'm glad we could finally do this. Thank you so much for joining us.

• 59:41Speaker 01

  Thank you for having me.

• 59:44John R. Miles?

  I hope today's conversation with Dr. David Perlmutter gave you a new perspective on something we have more influence over than we realize: the future of our brains. Our brains are constantly responding to the environment we create for them. And as David reminded us, the choices we make today shape what comes next. If today's conversation resonated with you, I'd love to hear your biggest takeaway. Share it with me on Substack, LinkedIn, or Instagram. And if you know someone who could benefit from this conversation, please send them this episode. If you haven't yet already, be sure to follow the show on Apple Podcasts, Spotify, or our YouTube channels so you never miss an episode. Because

• 1:00:26John R. Miles?

  this Friday, I'm doing something a little different. Instead of our usual solo episode, I'm bringing you a conversation with actor, entrepreneur, and father Josh Dummel. We talked about something that fits perfectly with our current series: how the environments we create can shape who we become. Josh shared why getting away from the noise of Hollywood helps him feel more like himself, and how becoming a father again completely changed his definition of success. I think you're really going to love this one.

• 1:00:56Speaker 02

  I know that however long I'm going to be here, I'm going to be totally present. I'm going to be totally in the moment. I'm not going to be thinking about anything but making sure that everything is working properly, because life just gets a lot simpler, I think. And I think that's what helps lower the blood pressures. I'm not thinking about all the other stuff, other than just what we're doing right here in the moment.

• 1:01:16John R. Miles?

  Until then, remember, the environment you're creating today is helping shape the person and the brain you'll have tomorrow. I'm John Miles, and as always, stay curious, stay intentional, and stay passion struck.

• 1:01:41Speaker 03

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