Feel Better, Live More with Dr Rangan Chatterjee - The Daily Habits That Protect Your Brain At Any Age: The New Science Of Dementia Prevention with Dr David Perlmutter #674

Episode Date: July 14, 2026

Most of us assume that memory loss and cognitive decline are just part of getting older. In this episode, a world-leading neurologist says that’s simply not true. That, far from being inevitable, Alzheimer's and other neurodegenerative diseases result from decades of metabolic damage – which we have the power to prevent and even reverse. I’m speaking with Dr David Perlmutter, a board-certified neurologist, six-time New York Times bestselling author, and one of the world's leading experts on brain health. And in this fascinating conversation, we discuss the single biological mechanism that sits at the heart of virtually every neurodegenerative condition, from Alzheimer's and Parkinson's to long Covid and depression, and why understanding it changes everything about how you approach your lifestyle. David’s key insight is that our brain's own immune cells, called microglial cells, have the power to make or break our future brain health. Keep them in their protective state through diet, exercise, and metabolic testing, and we can safeguard our brain for life. Feed them with ultra-processed food and they will shift into a destructive state that drives neuroinflammation. We discuss how, exactly, ultra-processed food damages the brain, why metabolic health is the key to cognitive longevity, and why the diagnosis of Alzheimer's is really the end stage of a process that began decades earlier. The choices you make right now, in your 30s, 40s and 50s, are already shaping the brain you will have in your 70s and beyond. If this all sounds science-heavy, rest assured David approaches it, just as he does in his new book, Brain Defenders, with clarity and plenty of practical takeaway. He outlines the specific blood biomarkers he believes everyone should be tracking, including fasting insulin, homocysteine and uric acid, for a remarkable window into your long-term brain health. We discuss why knowing your numbers is one of the most empowering steps you can take, how to go about getting tested, and how to act on what you find. There is a great deal of fear around dementia, and understandably so. But what I hope you take from this episode is something David emphasises: we needn’t be scared because we have agency. The research is clear that lifestyle choices have a profound impact on your risk, and it is never too early, or too late, to start making them. This is one of the most distinct and important conversations I’ve had about the future of your brain, and I think you will find it incredibly useful, thought-provoking and, above all, hopeful. The Thrive Tour: Transform Your Health and Happiness, a live show: Book Your Tickets https://drchatterjee.com/live   Thanks to our sponsors: https://heights.com/livemore https://thesleepreset.com/podcast https://boncharge.com/livemore https://exhalecoffee.com/livemore   Show notes https://drchatterjee.com/674   DISCLAIMER: The content in the podcast and on this webpage is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your doctor or qualified healthcare provider. Never disregard professional medical advice or delay in seeking it because of something you have heard on the podcast or on my website.

I think people need to grasp the fact that Alzheimer's doesn't just happen, you know, it's not a genetic thing by and large. It is a manifestation of our lifestyle choices and beyond food, that's for sure. The point is that should be empowering news for people, that this disease which people fear more than cancer is something over which they have a significant degree of control in terms of being basically the architect of their brain's destiny. Hey guys, how you doing? I hope you having a good week so far. My name is Dr. Rongan Chatterjee, and this is my podcast. Feel Better, Live More.

So, this will be the last episode in the current series of my podcast. And if you're a long-time listener, you will probably know that every summer we stop releasing weekly episodes for around six weeks. Now, there are many reasons for this, but the main one is,

because the summer is the time of year where my family and I try to prioritize undistracted time together. My wife is the producer of this podcast and so very involved like myself with the production of every episode. And so for us, we've discovered that this summer break is really important and something that we prioritize.

In fact, I would say that the more summers we do this fall, the more I realize that what we do is somewhat of a revolutionary act in a world that gives so many people the message that they can't stop. Now, I'm well aware that many of you really look forward to each week's episode and that this podcast has earned a place in your weekly schedule, and I am really, really grateful for that. But please don't forget that there are over 600 episodes in the back catalogue

and pretty much all of them are just as relevant today, as they were when they were first released. So perhaps this summer, you can take our little break as an excuse to delve into the back catalogue and listen to some episodes you may have missed first time around or perhaps revisit some of your favourites. And honestly, I think so many of these conversations are worth a second listen.

If you do go back and listen to an episode you've already heard, I could pretty much guarantee that you're going to hear different things. and that the ideas within the conversation will land with you in a different way. Because what we hear and pay attention to will depend on what else is going on in our life. After all, we don't see the world as it is, we see the world as we are.

Now, our plan, as always, is to relaunch the next season at the start of September. Okay, so on to brain health, which is the topic of this week's episode. Whether it's watching a parent struggle with memory loss or noticing that we're not as sharp as we used to be, the fear of cognitive decline is something I hear about all the time. Yet for far too long,

the message from mainstream medicine has been a disempowering one. That there's not much you can do about dementia. It's largely down to your genes so that one day, maybe, we'll find a drug to cure it. Well, today's conversation directly challenges that. My guest is Dr David Pilmutter, a board-certified neurologist, one of the world's most prominent experts on brain health, and the author of multiple best-selling books,

including his very latest, Brain Defenders, harness the power of your immune cells to protect your brain for life. In our conversation, we discussed the single biological mechanism that sits at the heart of virtually every neurodegenerative condition, from Alzheimer's and Parkinson's to long COVID and depression, and why understanding it changes everything about how you approach your lifestyle. David's key insight is that our brain's own immune cells, called microglial cells, have the power to make or break our future brain health,

keep them in their protective state through diet, exercise and metabolic testing, and we can safeguard our brains for life, feed them with a surplus of ultra-processed foods, and they will shift into a destructive state that drives neuroinflammation. We explore how exactly ultra-processed food damages the brain, why metabolic health is the key to cognitive longevity, why the diagnosis of Alzheimer's is really, the end stage of a process that began decades earlier

and the specific blood biomarkers that David believes everyone should be tracking, including fasting insulin, homocysteine and uric acid. There's a great deal of fear around neurodegenerative conditions like dementia, and understandably so. But what I hope you take from this episode is something that David emphasizes.

We need to be scared because we have agency. The research is crystal clear. The choices you make right now are already in real time shaping your future brain and it's never too early nor too late to start making them.

So I wanted to start off by asking you what is the effect of a high ultra-processed food diet on the health of our brains? Well, that's a great place to start. So what we know with respect to these ultra-processed foods is that they lead to metabolic mayhem. And I think, you know, you and I can unpack all of the pathways with which this metabolic mayhem is destructive in the brain.

But, you know, the bottom line is there's a metabolic underpinning for Alzheimer's disease. when you look at what people eat, there's a relationship to evaluating what people eat and their risk for a disease for which we have no meaningful pharmaceutical treatment. And interestingly, in the Journal of Prevention of Alzheimer's, let me pause right there. Think of it, a journal of prevention of Alzheimer's. For me, that's a huge step, that they would dedicate an entire medical journal to the notion of Alzheimer's prevention when, you know, so much in our world, world is really focused on the treatment of particular diseases. Anyhow, in January of a 2025 published an article that really evaluated over a 12-year period of time in 1,375 people followed them for 12 years as part of the Framingham Heart Study and basically followed what they ate. And what

they found was really quite important, I think, for our discussion today. That for every one serving of ultra-processed foods, whatever they were, these patients had an associated increased risk of Alzheimer's of 13%. And for those who were eating 10 or more servings per day of these ultra-processed foods, which here in America make up 60% of adult calories. Think about that. But if people consume 10 or more servings per day,

their risk for Alzheimer's went up about three-fold. Now, is this meaning that ultra-processed foods are causing this risk? You know, this is a retrospective study. It's a correlation, not causation. But if you ask me, and I think you are asking me, yes, and I'll break it down as to why I think these ultra-processed foods are so darn threatening. So, you know, I've been thinking about this for an awful long time in writing about it and lecturing about it because I think people need to grasp the fact that Alzheimer's, doesn't just happen, you know, it's not a genetic thing by and large. It is a manifestation of our lifestyle choices and beyond food, that's for sure. The point is that should be empowering

news for people, that this disease, which people fear more than cancer, is something over which they have a significant degree of control in terms of being basically the architect of their brain's destiny. Yeah, thank you, David. There's so many empowering messages that I think exist in 2026 about brain health compared to even 10 years ago in 2016, right? There's so much science, there's so much research. And the reason actually I started of this conversation asking you about ultra-processed foods is because I think there's been a growing awareness for some time that heavy ultra-processed food intake, it's not a good thing for health. I think a lot of people know that there's a relationship

between your rate of intake and obesity and things like type 2 diabetes and maybe your risk of heart attacks, but I still don't think it's common knowledge that the overconsumption of these types of foods has a detrimental impact on the health of our brains. And your new book, which I thoroughly enjoyed reading over the past 24 hours,

Brain Defenders, in the chapter on diet, I'll be honest, there was some pretty alarming statistics. You quote some research, David, that was published in JAMA neurology in 2022, where they followed more than 10,000 individuals for an average of eight years, and this is what you wrote in your book. Compared with the participants who ate the least amount of ultra-processed foods, those who consumed higher amounts experienced a staggering, 28% increase rate of global cognitive decline, meaning all areas of decline, including memory,

language, and attention. That is a staggering increase in risk, isn't it? It really is. And again, you know, critics would say, well, that's correlation. It's not causation. And I understand that you cannot say that, you know, the ultra-processed foods are causing dementia based on the study. I can say it, and I believe it, but from a strict scientific perspective, this is a correlation. But when we add these studies together in the aggregate, the study I just quoted you on ultra-processed foods, I don't think is in my book because it's quite recent. But having said that, you know, I think we understand that when type 2 diabetics manifest a 3 to 4x increased risk of developing Alzheimer's, and even pre-diabetic, we see the, we see the

relationship to insulin resistance and even mild elevation of blood glucose. And then we see what people absolutely understand, and that is the relationship of consumption of these ultra-processed foods to type 2 diabetes. And as you mentioned obesity, and obesity has a risk for Alzheimer's as well, everything really kind of falls into place. The puzzle pieces are absolutely falling into place still in a world that would like us to believe that we should live our lives come what may, and then when we develop an issue, there'll be a magic drug to fix it. That's the messaging in the Western world. I mean, I don't know how it is in the United Kingdom, but here in America, we have television commercials for one drug after another, and it's interesting because when you

take a look at what the drugs are doing, many of these drugs are what we call monoclonal antibody. or antibodies that are directed against inflammatory proteins used in a lot of autoimmune and inflammatory conditions. And it's quite clear that metabolic disturbances increase these autoimmune and inflammatory conditions through something called immunometabolism, meaning there's a direct relationship between our metabolic health and how balanced our immune system really is. I gave a lecture on that this past weekend in Chicago. How does immunometabolism, this notion that our metabolism plays out in our immune system,

how does that manifest in the brain? And it is exactly what brain defenders is all about, the fact that we have in our brain's immune cells called microglial cells, and they can be friend or foe. They can be supportive of our blood brain barrier and help us make new neurons and new synapse connections between the neurons, or they can shift and become the evil twin, where they destroy our synapses. They reduce our rate of growing new neurons,

and they damage the important blood-brain barrier. That shift between being the good twin or the evil twin is dictated by their metabolism, and their metabolism reflects our total body metabolism. Now, I've just said a lot, but let me collect the two outlying dots. they are that our body's metabolism determines whether our brain's immune system is going to support a good, wonderful, healthy brain, or is going to set the stage for our brain to be destroyed

based upon our metabolism. And here's the empowering part about what I just said. Our metabolism, each of our metabolisms, your metabolism is based upon choices that you make every day. So that's darn empowering that you have the choice to make lifestyle changes, to increase the value of your metabolism to ultimately affect your brain's destiny. So, you know, I know we have a lot of time together today to chat about a lot of different things. But having said that, what a message. I mean, that flies directly in the face of what we are being messaged. What we're being messages, as I mentioned earlier, just live your life however you want. and we will fix it. That doesn't work. We need to have the ball hit across the net to our side of the

court so that our destiny really depends on how we return that serve. Yeah, David, I've been thinking a lot about brain health over the past few months. I've had multiple conversations on this podcast with people like Professor Dale Bredesen, Dr. Tommy Wood, all kinds of professionals and researchers like yourself who are showing us from multiple angles that there is plenty we can do about this. This is not our fate, even if our mom and our dad or our auntie had Alzheimer's, it doesn't mean it's going to happen to us.

Now, what's really interesting, though, as I talk about this with my friends and colleagues, and perhaps this is my age, I'm, you know, in my mid to late 40s, David, but a lot of people I speak to will say back to me, I'm worried about my mum. I'm worried about my dad at the moment. It very much feels, so this is reaching epidemic levels, right?

The amounts of people who are struggling with cognitive decline as I get older is becoming so common that I believe many people think it is the norm, but it's not, is it? It certainly doesn't have to be the norm. Yeah, I mean, you know, people laugh away the idea of senior moments. And instead of Alzheimer's disease, they call it old timers disease. Well, I will tell you, I'm not planning on being there.

And I know Dale Bredesen's not planning on being there. And it's interesting, let me take you back a moment to what you just said. And you said, you know, my friends in my 40s are telling me about they're worried about their parents. My statement is that your friends in your 40s should be worried about themselves. because we know that the seeds are sown for Alzheimer's in terms of the metabolic threats to the brain in our 30s and in our 40s. So this is when we really need to start concentrating on an Alzheimer's prevention program. Because the metabolic changes that occur in the brain happened two, three, four decades prior to the clinical manifestations. When I say clinical manifestations, I mean the issues that people begin to recognize, loss,

sense of smell being something that happens very early, a loss of certainly memory, cognitive function, executive function, et cetera. But those things are late players, you know, they're late to arrive at the party. And, you know, my outreach now, you know, my outreach has really been to those people who are suffering and, you know, and hopefully their family members might, you know, get clued in on what I'm talking about. But I realize now that to really have an impact, because of the very epidemic that describe, we've got to be targeting individuals at a lot younger age and make them realize that, yes, what you just said is true that this is an epidemic in older people, but the way to prevent it is to target those individuals earlier in life. We know that, at least here in America,

that we have 30 million Americans adults with prediabetes. And, you know, the staggering thing about that fact is that 90% of them don't know it. So I really welcome and applaud the idea that there's direct-to-consumer laboratory testing now available here, and that means that people can't blame their doctor and say, well, my doctor told me I needed a fasting blood sugar every year, and it was pretty good, and he or she says, we'll see what you're doing next year. No, the people can be, again, in charge and can get their own fasting blood sugar, but be beyond that, get much more detail as it relates to the metabolism.

A fasting blood sugar is interesting, especially if it's really high, you know you've got a problem. But a predictor of fasting blood sugar elevation, even before it's elevated, is a fasting insulin test. And I'm very deeply involved in getting that message out that we should all know our fasting insulin levels and our hemoglobin A1Cs. And if you really wanna take it to the next level,

where a continuous glucose monitor, believe it or not, even if you're not diabetic, these are available without prescription. And not only shows us what our blood sugar is in the morning when we awaken, but also gives us a sense as to the dynamics of our blood sugar control during the course of the day, during the times during which we exercise,

what happens during a meal, after a meal, et cetera. These are very valuable inputs for us in terms of understanding our metabolism. And I would say if we want to raise in our metabolism that keeping blood sugar where it needs to be is absolutely job one. Why do I say that? Because all the other lifestyle inroads play out in terms of blood sugar, not getting enough sleep, exercise, stress. I don't know that lack of social connection is necessarily threatening blood sugar, but I bet it is. I'm certain if we were to look at

for a study about that, we would see it because a lot of people talk about it as it relates to reduce risk of Alzheimer's vis-a-vis, you know, the Blue Zone Studies, etc. And I think it's sort of, yeah, okay, you know, social connection is important. But let's talk about sleep and exercise. That's usually the conversation, but, you know, it's one of the important pillars. So I want to make sure we don't overlook that. Yeah, thank you. I completely agree.

Social connectivity is absolutely huge. And I think you raised a really good point, David, about this idea. that we should be paying attention to our brain health in our 40s, not just in our 70s when things start to go wrong, or we forget our grandchild's name or whatever it might be. I think I want to come back to that point. Testing for short. Before we go into those areas, though,

one of the things I enjoyed the most about your new book Brain Defenders is that you really set the stage at the top of the book about this one fundamental mechanism that potentially underlies virtually all neurodegenerative conditions. You've already mentioned the microglia immunometabolism, but I really want us to just really understand that because this kind of balance between M1 microglia and M2 is something I hadn't come across before.

And once you get that in your head, you can look at every single lifestyle intervention through that lens and go, what is this doing to M1 and M2? That's what the book's all about. You hit the nail on the head. It's exactly what we're talking about. And, you know, the polarization

of these microbial cells from being M2 supportive to being M1 destructive is a theme now that we're actually seeing elsewhere in the body. We've known that macrophages, the immune cells in the rest of the body, go through the same sort of shift

when they are metabolically challenged. We even know that chondrocytes, that are involved in either nurturing or destroying our joints, have an M2 supportive or M1 destructive configuration. So, you know, but when we see through the lens that you describe, the take-home message is empowering, because we control the levers that determine whether these microgleal cells are going to be on our side

or setting the stage for brain destruction. And I'm thinking of a slide that I use when I, in my presentations. In fact, with who you mentioned, Dr. Dale Reddison, three days ago in Chicago. And it is a type of brain scan that is called TSPO. And it's actually a brain scan that allows us to image activated, threatening M1 microglia when people are alive in vivo.

And when I show the image in Alzheimer's, you know, the brain lights up. But then I list the diseases in which this. T-SPO imaging is positive. In other words, microglia have been shifted to being the evil twin. And the list is really every major neurodegenerative condition you can think of, including Parkinson's, frontotemporal dementia, multisysmatory,

progressive supernuclear palsy, long COVID, PTSD, major depression. You know, there are a lot of things included that are manifestations of this shift in the immune system. And, you know, that's said, it sheds light not just on the neurodegenerative issues, but in the mood disorders as well, which we've known for many years

are characterized by increased inflammation in the brain, but now we understand why there's destruction, why there's destruction of the synapses, for example, in particular parts of the brain like the prefrontal cortex, because we're turning on these immune cells that are damaging the synapses. Yeah. Just to check, I've got this clear so far, Dave Eds. the microglia are the brain's resident immune cells.

When they become damaged for a variety of reasons, insulin resistance, toxins, infections, whatever it might be, they change shape and function. Ultimately, that causes a disruption in mitochondrial function, and that then leads to neuroinflammation, which sits at the heart of many of these different kinds of neurodegenerative of conditions. Is that an oversimplification or have I roughly... No, I'm going to actually simplify even further.

Okay. When there's a shift from M2 to M1, as you correctly stated, there's a phenotypic shift, a shift, in other words, they change their shape. There's a functional shift, as you describe, and there's a metabolic shift away from using the mitochondria to produce energy to another type of energy production that we call glycolysis. but importantly, one of the major inroads or threats that shifts the microglia is inflammation. The chemicals of inflammation called cytokines target the M2 microglia and shift them to becoming the evil twin. Those inflammatory cytokines can come from anywhere in the body.

When you get your arms around that, you realize then, oh, they can come from a leaky gut, When we have bowel disturbances, for example, that leads to increased inflammation in the body. These chemicals make their way to the brain and now help us understand why there is such a constant correlation between neurodegenerative conditions like Parkinson's and bowel disorders. Further, and here's where the story gets really interesting, these inflammatory cytokines are produced once those microglies shift to becoming the evil twin. So once we shift from being supportive and loving M2 microglia to the threatening M1 configuration, it, as you mentioned, increases neuroinflammation. What does that neuroinflammation do?

It further targets those good M2 microglia and shifts them over to being zombies. Think about that. So this explains now, we understand why a football player who no longer is playing football but yet has been diagnosed with CTE, chronic traumatic encephalopathy, gets worse over time, why Alzheimer's patients worsen over time, why Parkinson's patients continue to worsen over time, long after they've had their head trauma, long after they've had their exposure to a toxic chemical. We can talk about that a little bit later. I think we're teeing up an awful lot to talk about. But that said, it's because this spreads through the brain like a cancer.

These M1 threatening microgleal cells target the support of M2 microgleal cells and with time become dominant. So what you said is very true. But I think the important thing is that there is a shift in their metabolism away from the mitochondria doing the heavy lifting as it relates to energy production to a different form of energy production called glycolysis. So in a very real sense, we should be targeting mitochondria as we talk about in brain defenders if we want to do something very, very important. And that's the take-home message of our time together today. and that is that the microglia can shift back to being good. And that's our mission.

Yeah. Most of the messages are deeply empowering the messages. It's never too late. Having said that, going back to your chapter on diet when you were quoting some of the research that exists out there on the relationship between diet and brain health, I mentioned one of the studies that you wrote about. there was another one you spoke about, this 2024 study published in Neurology,

led by a researcher from Harvard Medical School, where they investigated the relationship between ultra-processed food consumption and brain health outcomes. And yes, as many other studies, that study concluded that there was a significant association between higher ultra-processed food intake and an increased risk of cognitive impairment. But I'll tell you what was really striking for me, David. A couple of paragraphs later, you write that, interestingly, when some of those patients adopted the Mediterranean diet,

the DASH diet, that dietary approach to stop hypertension, or the Mediterranean DASH diet, after the initial survey, the brain-altering effects of UPFs persisted. This means switching to a healthier diet can't always reverse the damage done. You just mentioned that, didn't you, that we want M2 microglia. If, for a variety of reasons, they start to shift to M1,

that's problematic for our brain, but then it's a feed-forward cycle where those M1 microglia themselves start to cause more M2s to go to M1. Could that be one of the reasons why when we change our diet, let's say after 20 or 30 years of a poor diet, that actually some of those brain altering effects might have persisted. Yeah, and I think, you know, when we look at what has been the goal of

pharmaceutical intervention for Alzheimer's disease, their goal, I mean, an ideal world would have been improving in cognitive function. But then they settled on, well, let's just see if we can stabilize people so they don't decline. You know, that's a reasonable goal for a patient with early Alzheimer's, but they even failed at that. I think that the idea of reestablishing cognitive function and improvement is going to require a much more comprehensive approach. We outlined a lot of things in the book that need to be added.

Diet is certainly one important pillar. A diet is really critical as it relates to reducing inflammation. But if we want to really boost the growth of new brain cells and the formation of new synapses, we have to target exercise as well such that we will increase the production of brain-derived neurotrophic factor in the brain or fertilizer, if you will, that helps also nudge these microgleal cells back from being M1, destructive to being M2 supportive. You know, if you look at Dr. Dale Redison's work, he talks about 36 things that need to be at least considered, if not targeted, to bring about actually improvement in brain function.

So, you know, the mission here is to indicate that there are multiple inroads that threaten these microglyle cells. We know that their metabolism is key. So metabolic health is certainly important. Inflammation is very important as well. Infections need to be considered. Toxic issues like metals, et cetera, need to be considered. All of these things attack the M2 microglule. So there are receptors on these microglia that then instigate the tissue.

change in their internal metabolism that leads to their shift to becoming M1. But I think your point is well taken. And Dale Bredesen makes it very clear that we need a multi-pronged approach if we're going to do more than stabilized, but if we're going to lead to improvement. Now, as we say that, that is something that can be achieved. I actually quote his work in the book and present a couple of his case studies, where, in which patients clearly improved and demonstrated not only improvement in their cognitive function, but improvement in the size of their brain's memory center, the hippocampus, on brain imaging.

That is black and white. These are read by independent radiologists who didn't know that there was an intervention and clearly described enlargement post-treatment of the hippocampus in these treated individuals. So the idea that the brain can't improve and cognitive function can't improve, I think is outdated. I think it takes a lot of work. But I think the beauty of what we are talking about now is it takes us away from hoping and relying upon something

called monotherapy. Western medicine is built upon this idea of one drug for one illness. And in Alzheimer's, it just doesn't hold up. And, you know, in Parkinson's, it doesn't hold up. We don't have any medications right now to treat Parkinson's disease. And that may be surprising for some of your viewers, but the reality is all of the medications that are approved for Parkinson's treatment are treating the symptoms.

They're treating the smoke. They're not treating the fire. I think these medications are excellent. I think that the ability of using Livo Dopa to help an individual with their rigidity in Parkinson's and some of the anticholinergics as relates to addressing. the tremor are valuable, allow people to continue on with their lives, but the disease continues to progress underneath that symptom-based approach readily. And maybe this sounds a little bit divergent, but in 2024, a fascinating study, and I talk about it in the book, was published in the New England

Journal of Medicine, 135 Parkinson's patients were randomized to receive a GLP1 OZempic-like drug. or a placebo for one year, and the results were dramatic. The group receiving the placebo continued to decline, as we would see in Parkinson's, but the group receiving the GLP-1 drug stabilized, in fact, slightly improves on what is called the Unified Parkinson's Disease Rating Scale, a standardized way of assessing how a Parkinson's patient is able to function in their daily life. So this is the very first time. Well, I'm going to actually say it's a second time.

I'll tell you the first time in a moment that the actual underlying metabolic issue in Parkinson's was addressed and look what they found. Now, I'll tell you about the first was actually our study in the 1980s using intravenous glutothion published in the journal Movement Disorders. Intravenous gluteothion was given also to improve mitochondrial metabolism. and our patients demonstrated pretty dramatic improvement on the very same scale used in the more recent GLP1 study. Let's be clear. I'm not saying that, you know, OZMPIC is the treatment for Parkinson's. That's not the take-home message from what I just described

because this GLP-1 was specifically chosen because of its ability to make its way into the brain. And in fact, now it's not available on the market here in America because it's been associated with some changes in the pancreas. But that said, what do GLP1 drugs do? Well, they don't just lower our appetite. They don't just control our blood sugar, the blood sugar control being why they were originally developed,

and now we're seeing a variety of other outcomes in people taking the GLP1 drugs. But one study that I did describe in brain defenders just mentions how in type 2 diabetics, mitochondrial function is improved in people using these GLP-1 drugs. That is huge. Because mitochondrial dysfunction is at the heart of what is going on in the Alzheimer's and Parkinson's brains and in all neurotogenic conditions.

I gave a talk at what's called the Institute for Functional Medicine, IFM, I know you're familiar with that group, 20 years ago where I said Alzheimer's is an acquired mitochondropathy. It means, you know, by and large, it's not inherited. We could talk about what that means in a moment. but a problem with our cells' energy-making machinery, our mitochondria. And again, we mentioned earlier, when the mitochondria become dysfunctional, that shifts our microgle cells from becoming supportive to becoming destructive. So we need to then take a step back and ask ourselves, again, thinking about what I just said about the GLP-1 drugs targeting mitochondria, again, I'm not saying this is our answer.

I did say in the book, and for those who read the book, the language I used was pretty strong. I'm open to it. I am absolutely open to it. I mean, you know, a lot of what my work is all about and yours too, really are the lifestyle issues that are, people are getting wrong and people can improve because that's very empowering. That's the take-home mess. People do these things and can have better health. But, you know, as are you, I am open to anything that fulfills the notion of risk-benefit ratio. And if the benefit of GLP-1 drugs in an Alzheimer's patient seem to be very favorable in the face of not such a significant risk, I'm all in. You bet I am.

That's going to be part of the toolbox. I think it's our duty as physicians to keep an open mind and put in our toolbox whatever satisfies risk-benefit ratio. That said, we will see what happens with GLB1s and the brain. We know that recently the study on oral ozempic, semaglutide, was published in Alzheimer's patient's interventional trial and did not meet its endpoints in terms of improving or slowing their rate of decline. That said, perhaps it was because it was oral and semi-glutide coupled that didn't make its way to the brain. But we will see. You know, researchers are hard at it, not just certainly looking at GLP-1s, but at a variety of ways of targeting not only mitochondria, which will help our microglial cells, but the microglial cells themselves.

Yeah. So many things you've touched on there, David, just to summarize to make sure everyone's sort of in the same place as we are in our heads. number one, metabolic health is crucial. You mentioned that maybe these GLP-1 agonist trials are demonstrating that actually when we address metabolic health and of course you can address metabolic health with lifestyle as well as with drugs, actually the impact on brain health is profound. You mentioned that often if we want to optimize our brain health,

there are multiple things we have to do, not just one thing, not just two things, but we have to address it from multiple different areas. You also mentioned about Dale's work. And, you know, I've like you, been a friend of Dale's for many years, and I went, I think it was in 2016, I went out to America to Palm Springs. And I worked with Dale for about 10 days on this deep immersion with patients. And I met some of his patients who have had their cognitive decline reverse,

and we worked on patients together for a few days. It was very, very inspiring to look at that research. This is 10 years ago now. So this is not as new as people think, this idea that actually there is something that you can do about Alzheimer's, particularly early stage Alzheimer's. You also mentioned, David, that there are cases of reversal, or at least reversal of symptoms. Of course, it's much easier to do that at the earlier stages. In the later stages, you know, it can get harder.

but I have seen it, David, like you have with patients, an early cognitive decline. And yes, we want to get involved way before that stage. But even at that point, there are things that you can do that make a meaningful difference in that person's life and their family's lives. We're going to talk about these things.

We have touched on diet and how important it is to take out ultra-processed foods as much as we can from our diets. So I guess the question I have for you, David, is, how have your dietary recommendations evolved over the years? And are there some sort of core principles that you can share with people to say, listen, if you want to keep your brain well for as long as you possibly can, this is what you should do when it comes to diet? I've done my very best recently to simplify the notion of dietary recommendations because

there are so many diets. There's probably a diet for every letter in the alphabet. whether it's paleo or primal or mind diet or med diet or green med diet. And I think it's very challenging for patients to think they need to adopt a certain diet and follow it to the letter in order to achieve an outcome. So this time around, and this is book number 16, I look not at the diet, but at the outcome. And I said that really I don't care what diet you want to, what name you want to attach to your diet. let's look at what that diet should do.

And to be very simple about it, because I think that's what people really need. Because when you try to adopt a certain diet and you have to have an app or follow-up book, it's very challenging. So I said, I want you to be on a diet that keeps your blood sugar under incredibly tight control that offers up your body a lot of dietary fiber,

in other words, is mostly plant forward, a diet that is colorful. so we're going to get lots of different polyphenols, and that emphasizes not only adequate amounts of protein, but good fats as well. Leave it at that. And I describe what adequate amounts of protein are in terms of grams per kilogram,

ideal body weight, and I also described in depth, as you saw, what are the good fats? That's it. So I wanted to open the door to people to embrace their ethnicity in terms of their food choices or not, whatever they choose.

Thinking about that, the idea of a Mediterranean diet, when you travel around the Mediterranean, you really see that they're not doing the Mediterranean diet anymore. I just got back from there, and it's, you know, this, we originally called it the standard American diet, the sad diet, which became the Western diet. Face it, it's the global diet now.

You know, just dramatically emphasizing ultra-processed foods, you know, your theme for our time together today. So this is a global issue, and it explains why there's 53 million Alzheimer's patients in the world right now, and that number will triple by 2050. So you call it it out as an epidemic, and it is. And it's something over which we have control. The fact that it's increasing so rapidly argues against it being genetic, because our genetics have not changed.

Our metabolism has changed. And I would add to that our epigenetics have clearly changed as well. As a matter of fact, we could talk about the work, interestingly, of a Dr. Sarah Marzi. She's actually in the United Kingdom. I had her on my podcast recently who's talking about how epigenetic changes are really underlying a lot of what's going on in the brain. We'll put a pin in that and deal with that later. But getting back to what you've been talking about.

So I'm trying my best to simplify these dietary. recommendations such that people can look at their diets in terms of how I am metacizing my body. In other words, what's the outcome of the food I'm eating on my blood sugar? Yeah. That is a leap. That takes you away from chapter and verse following a specific recommendation that a doctor has developed to actually looking at outcome. What is it doing to my blood sugar?

to me, and you might agree, I think that's one of the most important issues that goes awry when people are eating inappropriately. So, you know, really emphasize for people the idea of knowing what your blood sugar is. Even if you can't get a continuous glucose monitor, go to the pharmacy and buy a finger stick. It's available to anybody,

and I know it's not pleasant sticking your finger, but do it once a month and see where you are. But it's really that important. Again, the fiber for the mind. microbiome, the polyphenols, we could talk about that in terms of why that's important for the brain. The right kind of fat gets back to your original question, what has changed? I think one of the biggest change that I emphasize now that really was not emphasized earlier, very, very early in my career, frankly, respectfully, before you were born. And that is, you know, the position on fat.

I mean, there was a time when fat was not the right thing to be eating in any form. And, you know, that was what the science was telling us. And I, you know, in mainstream medical training was parroting that. And that changed obviously and for good reason over time in my outreach that, you know, fat is a fundamental player for metabolism, for inflammation, for structural integrity of the neurons, you know, a variety of things that the right. ripe fats do in our bodies. Yeah.

I really like the guidelines you provided for food there, David, because ultimately, whatever diet you follow, there's a certain outcome that we're looking for, right? You know, one of those outcomes is a well-controlled blood sugar, right? So you can get that outcome in a variety of different ways. So I kind of feel this is a good time to talk about testing. One of the things I really enjoyed reading at the start of Brain Defenders was this idea that there were two wars that we're fighting at the moment. One is, I think, the war as to why are millions of brains around the world, as you say in the book, On Fire.

But then you also said the other war we're fighting is on our attitudes, our attitudes about illness and expectation. And I thought it was a really provocative thoughts, but a very important thought because that's what we're up against, aren't we? we're up against a medical system that has made amazing inroads into certain conditions that many of us have grown up with and absorbed the idea that if you get sick, the medical system will be there to take care of you. And as we're realizing, for many of the conditions that now are affecting a majority of the world's population, these are chronic diseases that take years to build up in your body. As you said earlier on, David,

maybe 20 to 30 years before you get a diagnosis of Alzheimer's, that process has been going on and causing havoc in your body. You know, the diagnosis is the end stage, right? That's right. Of a long process. And that really ties into what you're saying about what diet you want to follow is the diet that gives you a certain outcome on certain biomarkers.

Now, David, one thing early on in my career, I did back in maybe 2012, 2012, 2013, 2014, I would go to America a lot in my vacation time to go to conferences and to learn stuff that I felt I didn't learn at medical school. A lot of the good conferences back then were certainly in America. And what I noticed from chatting to a lot of American physicians is that the American medical system, is fundamentally very different from the UK one. And it's very obvious now as I look back, but what that led to is for many years, David, I was hoping that the NHS, our National Health Service,

would really take on the mantle of prevention. And unfortunately, a few years ago, I realized that, you know what, I actually don't think that's ever going to happen because the DNA of the NHS is to manage disease. And I think often it does that very, very well, and the NHS's idea of prevention is once you hit the age of 40, maybe every now and again go in and get your blood pressure checked and maybe once every five years get some bloods done.

That to me seems like prehistoric prevention compared to what we know. So what I did about a year ago, David, I don't know this yet actually, about a year ago, I thought in the UK, we're in a position where people who are interested in health, might listen to my podcast or your podcast or read books and go, yeah, you know, I need to check my fasting engine. I need to check my homocysteine, my uric acid, the topic of your last book, right?

Who knew? Yeah. Ben, we'll tie this all up in a minute. But actually, they would listen to these conversations or read our books or other people's books. And then they weren't able to get that, certainly in the UK, from their NHS doctor. You just can't get, for most people a fasting insulin or a homocysteine on the NHS. Now, there are private providers where if you were really motivated, you could put together the correct panel. But, you know, there's a lot of work on your shoulders in order to do that. So I teamed up with some amazing tech guys and created something called Do Health,

which I don't think there's anything like it in the UK. And basically, we don't do like a, you know, test hundreds and thousands of of biomarkers, we've started small and test the 11 biomarkers that I believe are the most impactful when it comes to metabolic health. And we give daily and weekly lifestyle advice on what you can do around them, like all of these 11 biomarkers, we know impact your metabolic health, your short-term health and your long-term risk of disease. But at the same time, they are 11 biomarkers that are all amenable to change. Those are the criteria.

It's only been live for two and a half months, but the feedback, David, is absolutely incredible because, A, it's very, very cost-effective for what it is, but we have basically gone, I think, talking about the sort of stuff you're talking about, right? We're checking stuff like fasting insulin, homocysteine, HBA-1C, ALT, B-12, uric acid, and I won't do the whole list,

But I would say that your book, your last book, heavily influenced my decision to put uric acid in this panel of 11, so first of all, thank you. But I think what it means then is whatever diet you follow, as long as it's generally a whole food, minimally processed food diet as much as you can, if you are getting these biomarkers in the correct range, right, a low fasting insulin,

And HBA1C maybe under, I don't know, 5.3, 5.2, whatever it is. You know, if you're home assisting in the normal range, then actually, you know that whatever lifestyle you're following, the key markers that influence metabolic disease are actually, you know, in good shape. And we've decided to recheck twice a year, well, three times a year. So it's like you test, you do four months of lifestyle change, and then we recheck. Because, of course, this isn't just a one hit.

So, first of all, I want to get your take on that, David. Do you think this is the kind of approach that we now need if we really want to get on top of our brain health? And then I guess secondly, from what I've said, are there any downsides to this kind of approach? Well, let me answer the second question. First, I can't imagine any downside. You know, costs will have to be considered. But, I mean, everything that you mentioned on that short list has huge, play in terms of brain health. And, you know, it impacts metabolic health in the body,

and the brain isn't distant from the body. It's part of the body. It's going to be the same impact on the heart, on the liver, on bone density, which is reflective of metabolic health. Who knew? And, you know, my only time visiting your country was several years ago when we met, And it's interesting because I was asked, I was summoned to visit with then Prince Charles, and we sat at High Grove, I guess it's called, and he asked me the question, what is the reason that our health is deteriorating? And the answer was very simple, ultra-processed foods. And I looked from a straight at it.

I said, that's what's going on. And that's what you need to address. And he said, well, I don't know how I'm going to address that. And I don't think there was really any outcome of that meeting. But I think that's what we're up against. And I think, you know, the food industry has no interest in health. And health care really doesn't spend any time involving itself in food. So this is a huge disconnect that has never been present in humanity.

Yeah. Traditionally, food and health have always been linked. and it's I remember years ago I was somebody accused me of my practices being non-traditional because I was talking about nutrition and the brain. I said that's really non-traditional. And actually, interesting, it was a time when I was supposed to be the chairman of neurology at our local hospital is my turn. Nobody even wanted the job.

And one of the individuals in the group said, well, we can't have Dr. Perlmutter do it because he's doing these non-traditional things like nutrition. And I, you know, I'm thinking, you know, humanity has always valued the food that we eat and its relationship to our health and its relationship, importantly, to our connection to the planet as well, which is really something I think that we no longer value and even recognize. Well, not we, but, you know, generally in the world, there's no connection between the fact that the planet is giving us this sustenance. all food comes from the earth, whether you're vegetarian or not. You know, because ultimately, plants are the source of food,

even for the animals that people eat, with the energy ultimately coming from the sun for all of it. So, you know, I think I was a little bit divergent on my response to you, but I think that it is very challenging. I honor what you're doing because I think what you're doing is simplifying. You know, there are organizations here in America that offer 400, different labs. And it's overwhelming, in my opinion. Yeah, David, you raised a key point there. So I'll be honestly, I never had any plans or desires to launch a health app, right? But I just thought

there are so many people out there who want to know their biomarkers so they can make changes and see what changes are working and which changes are not working, which is why I think tracking. By-markers and re-checking them is so important because, A, you can be making some changes to your diets and not getting the drop that you might want to see in your HBA-1C. I accept. There are other factors like movement and stress and sleep, but it might be that, oh, maybe the diets you're trying at the moment isn't the right one for you. Maybe, you know, maybe you're really insulin-resistant. And actually, you need to drop- That's so personalized. I'm just loving what you're saying.

it's so personalized because maybe that diet isn't the right diet for you. Yeah, maybe you heard about the evidence on the latest podcast you listened to and thought, great, but when that diet interacts with your biology, what is the outcome on these key biomarkers? And so I kind of feel that this is not a slight on the NHS. It's basically saying, look, let the NHS do what the NHS is really good at. Let's create something that I hope is the future of preventative health in the youth. And I specifically insisted on small amounts of biomarkers, right? Because I think it can become overwhelming.

Over time, David, I'm sure we'll add to these biomarkers. But we've started where there's 11 biomarkers, there's damn good evidence for all of them. I think that's a home run. I mean, look what I did in this book. I said one biomarker. I mean, we look at a lot of biomarkers in the book. I talked about homocysteine. and GFAP, P-Tal-217, you know, other things.

But in terms of your diet, I just wanted to control your blood sugar. And having said that, and you make the changes, and your blood sugar is recalcitrant. It's still not coming around. You know, you might need metformin. You might need a medication. So that's the point here. And I think what you alluded to is the notion of personalized medicine

that this person may have adopted a specific diet, and it's not yet controlling her blood sugar. So the uniqueness there is this notion of personalized medicine based perhaps on her genetics and other aspects of her lifestyle as well, the variables like exercise, sleep, et cetera. That is just not enough, and she would not know it's not enough unless she is testing. Exactly.

We have that ability now. We should welcome it. and use this information that we have. And we can, through guidance like you're offering, be stewards of our own health and really adopt more salubrious lifestyle choices based upon the input from this information. So I think what you're talking about is an absolute home run.

David, I've heard you previously talk about the fact that your home assistine was previously elevated and that you take B vitamins to manage that. I know you write about homocysteine in the book as an important biomarker we should all be looking at. I wonder if you could just touch on why you think homocysteine is so important, but also if you could remind us, for those people who didn't hear my first conversation with you, why is uric acid an important biomarker to look at as well? Okay, let's start with homocysteine.

And my homocysteine as of yesterday was 8.2, and that makes me very happy. So, you know, it's been said that why should I take supplements after all? I can't measure that they're doing any good. And I always, you know, people have asked me that question when I give a lecture, whatever, and I always challenge that because, you know, the notion of a supplement means it's something added to to supplement because of a deficiency or a need. That's why we take certain supplements. And so in my case, I had a need.

I had an elevated homocysteine. I'll describe what that means in just a moment. But the reason that I have an elevated or had an elevated homocysteine is because of my unique genetics. I carry something called an M-T-H-F-R polymorphism. Now, that's a mouthful. It simply means that I don't handle B vitamins in a good way when I consume B vitamins either in a supplement or getting them in food or perhaps even the ones created by my gut bacteria, such that I'm not able to methylate. It's a biochemical change that activates,

let's say, and makes them work worthwhile, a certain B5, B6, B12, and Foley, folic acid. So I have to add, and that is the reason that my homocysteine level is elevated. So I take these, I take foliate, I take, rather, methylidate, to folate, B-12 sublingually, and a B-complex, and every once in a while a B-12 shot. And lo and behold, my homo-sitin level has come down. I don't feel any different. I feel happier, right, and more confident, but I don't, I can't feel. So I'm like, oh, gosh, I've been taking these vitamins now.

I have more energy and, you know, my life is great. That's not what you're looking for. You're, again, getting back to the idea of looking at your biometrics like you described with your testing. So, homocysteine has been, elevated homocysteine has been directly correlated with dramatic increased risk for Alzheimer's, even cardiovascular disease as well. We've known for a long time that homocysteine poses a threat because it is converted in the body to something called homocysteic acid.

Homo cystic acid does two things that are very important. It damages the lining of blood vessels, hence the cardiovascular risk from elevated homocysteine, and it is a mitochondrial toxin, home run. So elevated homocysteine is threatening mitochondria and therefore threatening whether your microglial cells are friend or foe. That's why Dr. Chatterjee is adding homocysteine to his very short panel of critically important blood markers. And I applaud you for it because I went to a cardiologist yesterday.

I do see a cardiologist. I had atrial fibrillation in the past, did well after a cardioversion, after an ablation procedure, home run. But I mentioned homocysteine, and he said, I'm going to have to send you to a different cardiologist

who knows about that kind of stuff. And I was grateful that he would refer me. But homocysteine is a player. I mean, it really is a player. If 28% of people in Western cultures have this, MTHFR genetic variant like I do, 28% of people are at great risk for having an elevation

of this homocyte that is a brain threat, then darn it, they need to know about that and fix it by taking simple B vitamins. Yeah, David, I just wanna comment on a couple of things there. First of all is this idea that, well, you may have checked your B12 levels, right? But in some ways it wasn't necessary in the sense that your homocysteine was elevated. We know that an elevated homocysteine increases your risk of dementia and, as you say,

other conditions as well. So therefore, you need to do certain things, like take methylated B vitamins to bring the homocysteine down, irrespective of your B vitamin levels. It's a subtle difference there. You're taking. the nutrients to drive the biomarker down, and by driving that biomarker down, you're reducing your risk of getting sick. Yeah, let me simplify that if I can. Sure. If you have your B vitamin levels checked and they're normal, it's not good enough because you're not, you might not be deficient in those B vitamins. You might be deficient in the methylated B vitamins, which you can't really test for, but the homocysteine is a proxy for that. Maybe that made it more complicated.

No, no. I think it's great because it's not the way I think people think about nutrients, right? So I think that's really useful. I do want to talk about uric acid, but I thought just came up for me, David, which is, I believe that you are in your 70s now. Is that correct? 71. I'm 71. Okay. I remember meeting you in London two or three years ago. You were sharp, bright, right, right on the money. You gave a great talk. We did. a lovely podcast together. I see you now at 71, having written, I think you said, what is it, 18th, 16th book? This is number 16th, correct. Your 16th book.

I think for many of us, it's inspiring. I think a lot of us would go, if I could have the sort of cognition and brain that David Pilmutter appears to have at the age of 71, I'd be very happy with that. And I think that's very relevant in the context of what we're talking about, which is our brain health getting worse

as we get older, what do you attribute your apparent exceptional brain health to? I think you just mentioned it a moment ago. You said curiosity. And curiosity has been powerfully motivating for me throughout my lifetime. I'm really trying to understand, okay, you know, there's a paper written that shows this correlation, but why? What's underlying it? And I think satisfying that curiosity has been the development of this idea that all of our inputs for things like Alzheimer's risk converge on the brain's immune system. So that's, you know, connecting dots has been something really central in my life, as has been the idea of compassion that I learned from my father, a brilliant neurosurgeon, brain surgeon, who, as fate

would have it, died of Alzheimer's. That was a powerful event in my life. And it solidified. my desire to learn more. Robert Kennedy, Sr., said years ago that some people see things as they are and ask why. Others see things as they could be and ask why not. And I love it. I just love it. Because medicine puts, has traditionally puts constraints on outliers like you and me and, you know, many of the people who have been on your podcast and on my podcast. And I think we're starting to get to a place where we're starting to value a little bit, the idea that, you know, maybe people are onto something. And I think the notion of lifestyle influencing brain health is really gaining a lot of traction right now. So I keep my brain aggressively engaged,

not as I don't do that as I exercise. For example, I mean, in other words, I dedicate time to exercising each day. I don't say I'm going to do X amount of reading and, you know, writing each day because it's good for my brain. That's just part of my, what I do. So it's not one of my lifestyle choices. I don't know if I made that clear, as are the foods I eat, the sleep I get, you know, metacizing all these things. So I'm grateful to hear you say that you think I'm still in the batters box. That's encouraging. Let's get together when I'm 81 and we'll reassess where we are. Yeah. David, David, what I hear from you there. There are so many sort of beautiful things about curiosity, compassion,

thank you for sharing about what happened to your father and how influential that has been in terms of what you do today. But it sounds to me as though so much of what you do is an expression of who you truly are. And I think this is where we often go wrong with behaviour change. My philosophy on behaviour change is that, yeah, I guess at the start, it can be tricky, right?

But I think the missing link in behavior change of many people is that at some point, I actually think behavior change or adopting healthy behaviors becomes quite easy and effortless when it truly is an expression of who you are, when there's full alignment with the person who you are and the person who you are being out there in the world

are one and the same, I kind of feel that your behaviours follow suit. So I obviously don't know the intricacies of your life, but you write about empowering us to have better brain health. You've treated so many patients and helped them. And it strikes me as though you can't really write about this stuff and be curious about this stuff and not also do it yourself. There would be a complete misalignment between what you were writing and your behaviour.

So it strikes me, though, you do have a wonderful lifestyle, and you're engaged, you're curious, you enjoy what you do. And so it all kind of fits together instead of it being that, oh, I'm trying to make lifestyle change in conflict with the person who I believe myself to be. Well, I really want to be not be that person to do as I say, not as I do. and many of the things that I choose to do, then I articulate if they're effective and achieving a goal. But going back to what you were speaking about earlier, I would, I focus not on who I am as much as who I want to be. And so there's still plenty of work to be done.

And that's what life is about is doing that work and focusing on those goals. you know, the Dalai Lama said, if you want somebody to be happy, want others to be happy, treat them with kindness. And if you want to be happy, treat others with kindness. So I think that maybe it's self-serving then, and that's okay, that if you do this work and you see the outcome, that it's good for you. And that's self-serving, and I'm the first to admit that. We wrote a book, my son and I, two or three books ago, called Brain Wash.

And it really focused on something you just touched on, and that is our decision-making. What do we decide to do once we have information? Are we able, you said, then it gets easier. And we focused on the hardware of decision-making, if you will. what are the mechanics of decision-making, and really try to distill that down to two important brain areas, the amygdala, which leads to our rapid decision-making that is really pretty self-centered,

doesn't look at future consequences, doesn't look at impact on other people, on the planet, et cetera. I want to do it. I want to do it now, and that's it and a story, versus bringing into the decision-making process an area of the brain called the prefrontal cortex, which for our discussion can be looked upon as the adult in the room. That is measured, says, hang on a second, how is this going to play out in terms of your life moving forward, how does it affect other people, is empathy involved, etc.

The prefrontal cortex, as we reach our teenage years, begins to exercise control over the more impulsive amygdala-type brain activity. It exercises what we call top-down control, or what I like to say, the adult comes into the room. The pathway that connects and allows that top-down control, called the anterior cingulate, is threatened by inflammation. And that has huge implications.

What causes inflammation in the human body that would then lead us to be more impulsive, less empathetic, and more self-centered? Ultra-processed foods. So the pervasive consumption of pro-inflammatory foods globally is segregating us away from the gift that we have of this wonderful prefrontal cortex allowing us to conceive of the future and consequences and be empathetic beings and locking us into being this narcissistic self-centered instantaneous decision-making apparatus called the amygdala.

It has its upsides. We need to make rapid decisions. at times instantaneously and not think about things. When you're backing up your car and in the rearview mirror in the camera, I used to do something called the rear view mirror for some of you younger people. That was it anyway. But you see a kid on a tricycle, you don't think about it. You step on the brake instantly.

That's an amygdala response. But to live your life in fight or flight and making decisions based upon the amygdala doesn't have good outcomes, even as it relates to your lifestyle choices. So what I've just done is created a feed-forward process whereby when we eat what you are so focused on, these ultra-processed foods, increased inflammation in the body, it takes us away from better decision-making. What does that do? We continue to eat those foods.

We continue to stay up late. We continue to lack exercise, sedentarity. And that just builds a situation whereby we're paving in my world the way for brain degeneration. But the simple part that you, I think, touched upon is that any inroad that can allow us to re-explore and value and utilize this prefrontal cortex as playing a role in our decision-making and exercise this top-down control will ultimately allow many other lifestyle choices to come online and pave the way for a better life. So it really does come down to the nuts and bolts of our decision-making.

apparatus. Yeah, that is so interesting as to the impact of inflammation and ultra-processed food consumption on our ability to make the right decision. So maybe it's, yeah, at first it might be a bit tricky whilst you're changing over your behaviours. But as the inflammation starts to come down, you know, your decision-making will start to improve and you may well find it easier and easier over time to make certain changes. David, let's come back to uric acid. That was the topic of your last book. Why is uric acid an important marker for us to look at when we're trying to assess our metabolic health?

The next sentence I think is very important. Uric acid tells your body winter is coming. What does that mean? It means that elevation of uric acid does things to pave the way for your survival, during times of caloric scarcity, meaning increased fat production, down-regulating mitochondrial function, increasing blood pressure as a hedge against not even finding water. So this is a genetic change that happened in Proconsul, one of our primate ancestors, around 8 million years ago, a change such

that uric acid would be increased when our ancestors, our primate ancestors, our primate ancestors, said there's ate a certain food that would be present in the late fall when winter is coming. Something is in the food in the late fall that triggers the body's production of uric acid that sets into motion this survival pathway. And what is that trigger? It is fructose, fruit sugar. When does fruit ripen? It ripens in the fall before winter.

It's a beautiful bit of chronobiology, isn't it? that, you know, we're in harmony with the planet. The plants finally ripened there. You know, the starch turns to sugar, fruit gets sweet. We love sweet. We're hardwired to love sweet. We eat the fructose and fructose is directly metabolized to uric acid. That is a powerful signal to our metabolism to prepare us for winter. There would be selection of those individuals who had higher uric acids for survival because they made more body fat and they had a depot for caloric reservoir so they could survive during times of caloric scarcity when others who didn't have high uric acid would die where are we today we're in that same situation where we still have the

lack of uricase enzyme the enzyme that breaks down uric acid such that we as humans accumulate uric acid higher than any other mammal. And that uric acid is directly leading to fat formation by changing cellular metabolism. It's directly involved in damaging mitochondrial function. It is elevating our blood sugar and elevating our blood pressure as well. Inhibiting nitric oxide

and as such leading to inability of blood vessel to relax by its inhibition of nitric oxide. It is down-regulating the effectiveness of insulin. So where is the fructose coming from? Well, fructose is the number one natural additive sweetener to food. You know, more than 80% now of foods in America's grocery stores have added sweetener. And by and large, that sweetener is fructose or a combination of fructose with other sweeteners. Why? Because it's really sweet and it's really easy to make and it's cheap. So we make fructose from corn, high fructose corn syrup that is just, you know, across the board,

ubiquitous in foods to make them palatable and tapping into this ancient desire survival mechanism that we have for sweet foods. So we recognize that uric acid, when elevated, is a powerful metabolic destabilizer. That higher uric acid levels are linked to all cause mortality. They're linked to development of dementia and they're certainly linked to development of metabolic issues like diabetes. So I think it's reasonable and to understand what is your uric acid level. And I think you mentioned you're going to include that in your 11 item panel. And you absolutely should. You know, people, it takes us to an interesting discussion of in the normal range. What does that mean? Oh, I got my labs back and everything was in the normal range. Oh, but

The labs I got last time, I had something that was out of range. And my doctor said, I should be careful, it was my B12 level was too high. And, you know, I don't know why I'm focusing. And vitamin D level was out of the normal range. Well, I think that clearly what you're going to do if you're not ever doing is, is recontextualized this notion of normal range. Normal range is average. It's two standard deviations from the mean, looking at large population sets, large data sets.

average and what is average is not necessarily what is best we want people you want people to be in the optimal range in other words what is best blood sugar of 100 is not good enough no way that's just not good enough for for your messaging and my messaging we want people who are listening to us today and will continue to listen to you and pay attention to your app to really focus on what is optimal not just what's good enough yeah absolutely thank you for sharing the important of uric acid. And I completely agree, you know, there are normal ranges, there are optimal ranges, and certainly with due health, we're helping educate people as to where they are now, where they could get to, and we're going to help them along the way to get there. David, I want to go back

to the central message of brain defenders, which is we want to, as much as possible, keep our microglial cells in the M2 form and not have them go to the destructive M1 form. We've touched in terms of practical applications to people. We've spoken about some dietary principles. I wonder if we could go through some sort of practical take-homes for people, but through the lens of M-2 and M-1. So, for example, people know that exercise is good for their well-being. how exactly is exercise good for the brain and what does exercise do to our microglial cells?

I'm going to answer that question in one moment, but I just want to get a little bit broader perspective because I'm often asked, what is the one thing, the number one thing you can recommend for people to help them chart their brain's destiny for the better? And that one thing is to embrace the idea that you are in charge with regard to these choices, with respect to your lifestyle choices. Yes, sleep, yes, exercise, yes, diet. These are all connection, social connectivity, important. The most important thing is to recognize that you're in charge. You control your brain's destiny. Now, as relates to exercise, we've known for an all of a long time. People have said, yes, exercise, good for your heart, good for your brain. And it brings to mind just one other thing that's, I think,

And that is that nobody talks about a brain-smart diet, but for how many years have we heard about heart-smart diet, right? There's even, I think, a label that goes on certain foods. This is a heart-smart food. Why not the brain? It's the same thing. We're talking about inflammation, free radical stress, and it's the very same diet.

It's no different. But let's go back to exercise. I've had a cup of coffee, as you can see. We have to look upon the muscles. which are the active player in exercise, obviously, and the brain. But look upon the muscles as being an endocrine gland, and that will raise eyebrows. You know, people consider the endocrine gland,

well, the adrenals, you know, the pituitary, the ovaries. These are our endocrine glands, and by definition, the endocrine gland is a part of the body that creates messengers that go elsewhere in the body and do certain things, right? The pituitary sends out things like growth hormone, that do certain things. Adrenal corticotropic hormone

from the pituitary challenges our adrenal glands to do certain things. But the muscles indeed do exactly that. They secrete chemicals when they are active that do really good things throughout the body. They are, you know, cathepsin B, eryssin interleukin-6. Oddly enough, we tend to think about that as being a pro-inflammatory cytokine,

but actually does some great things. These chemicals go throughout the body and even into the brain and do good things for us. Importantly, something called ERISN gets into the brain and stimulates the brain to produce something called BDNF. I spoke about BDNF, brain-derived neurotrophic factor earlier. You really want to have a lot of BDNF in your brain because BDNF nurtures the neurons,

nudges the microglia back to being supportive, and therefore nurtures the formation and preservation of our synapses and yes, even the blood-brain-brain barrier. So we want this BDNF to be present. We know that there are higher levels of BDNF when we exercise, and that was demonstrated way back in 1988 by Dr. Erickson, University of Pittsburgh, who correlated exercise in a one-year interventional trial

versus simply just doing some mobility work, but actual aerobic exercise with not only increased BDNF, but also increased size on MRI scanning of the brain's hippocampus showing that exercise caused growth and also improved memory performance. As a consequence of exercise, since that time, multiple studies that have come out, studies demonstrating a correlation between the number of steps you take on a daily basis and your risk and or rate of cognitive decline, simply taking steps. The magic number was oddly enough close to that 10,000 that we often hear,

bat it around as being the ideal amount of steps to take in a given day. I think there are benefits to both aerobic exercise as it relates to producing that BDNF and also resistance exercise simplistically to increase the size of the pharmacy. So there's more muscle mass there to create these really supportive chemicals

for total body health and for brain health as well. So, and I actually describe this in the book, that really what has been demonstrated in research that looked at what is best, aerobics or resistance, answer both, all the above. Do you really want to have, I actually say there should be three. And just to be kind of conjectural, and that is, I think we definitely want to have flexibility exercises as well. Why?

Because I think we need to remain flexible, so we reduce our risk of injury. If you become injured, then all better. are off. You don't can exercise anymore and, you know, that whole program is postponed. So I think flexibility, stretching really important. I like balance exercising as well, keep you from falling, again, hurting yourself. But the main players are the aerobic and the resistance training. So what do I do? I go to the gym three times a week and do weights. I tend to like the machines, but I do some free weight work as well with dumbbells on an incline board, inclined bench. I'm particularly fond of the ab machine, and then I use a variety of other machines. But I stretch first, and I actually use a

power plate. I think their data is solid in terms of improving a flexibility and yes, balance. On the other days, I either run or walk or use an elliptical machine, but right now I've gotten a new stationary bike that I am totally thrilled with. It gamifies exercise. I'm on the stationery bike and I'm having to do these various games, which are fun and I want to win. And at the end, they show you the leaderboard. And, you know, I've gotten up to, I think, number three on the leaderboard, no, number four. And I'm the old man. So I did an Instagram post saying, hey, for you who are using the Averon stationery bike or treadmill, that David P, that's me. I'm number four on the leaderboard. Don't let the 71-year-old guy catch you.

But anyway, so for me, gamifying has been very helpful because 30, 40 minutes go by quickly because, you know, a machine like that can be boring. That's why I like to be outside and run because then I can see things, breathe fresh air, you know, see people wave at them and experience nature. So that's what my program looks like in. I'm sticking to it. Yeah, David, thank you for sharing what you do. I think, obviously I can't know this for sure, but I would imagine there are going to be some people listening to this conversation

who are thinking, I wish my mum or dad in their 70s was doing what David is doing. And the reason I say that, I just want to really highlight this point that, yes, we've used some technical language at points during today's conversation, right? really try to help people understand the science that exists behind your recommendations and everything you talk about and brain defenders. But on a human level, this is very, very real.

People's lives are being so devastated by family members having cognitive decline. A, you know, on a sort of individual intersocial level, it can be very frustrating to see that happen to a loved one. that can be significant financial implications for families when it comes to how do you look after people with cognitive decline? Do they need to sell their house, go into some kind of facility? These things are incredibly worrying for people, yet the central message behind so much of what we're talking about today

and frankly, what both me and you have covered on our various platforms for many years, it really doesn't need to be that way. There are things, it's not as difficult as you think it is, there are things that you can do that are going to really make a difference. But I do think, David, there may be a generational issue here in the sense of, you said before, right?

We spoke about this war on our attitudes. I saw a good mate of mine this weekend. And his mother, unfortunately, is starting to decline cognitively. And she's going to see her conventional doctor. And really, you know, as well as I do, that you go to your conventional doctor, you're generally told that there's not much you can do about this.

There is an inevitable decline. You know, yes, they might put you on a waiting list for things and check your blood pressure and your blood sugar. But there's not much practical guidance. And I was chatting to my buddy, and he said, wrong in everything you're talking about, I'm trying to share with Mum, but she's not listening. You know, she drinks half a bottle of wine every night and has them for many years.

That's just part of her lifestyle. She's unlikely to change now. And I think, David, there's a really key point here, isn't there? Which is, look, I'm learning this information at an earliest stage in life than perhaps you did because the science is there, right? So I'm able to really implement a lot of this stuff in my 40s, and hopefully that will continue for decades, right? But there was a generation, and maybe you're part of that generation,

but perhaps because of the way that you think, your curiosity, your practice, you've ended up in a different state of health compared to many of your peers. But I think my friend's mother, there are so many people out there like that. They think this is inevitable. And, you know, what advice would you give to people like my friends who say, Ronan, I'm listening to this information, I'm reading the stuff, but I can't get my parents to put the advice into action? I think it's very challenging because my generation and his mother, again, we were brought

up to think that our lifestyle choices didn't matter, do whatever you want that you like, you know, cater to your desires, and modern medicines got the fix. And don't worry about it. They'll fix your heart. They'll fix your brain. You know, and that's just an incredible mismetaging that, you know, really characterizes what you're talking about here. You're right in your observation of people in my generation because they're very difficult to convince and to prevail upon in terms of, you know, what your friend is up against with his mother and, you know, that's pervasive. What I would say to that individual is, look, do the best you can,

but let's talk about you. Because I really think that it's, the bigger play here is the 40 year and 50-year-olds, 30-year-olds, that, you know, John Kennedy, President Kennedy said during his inaugural dress, that the time to fix the roof is when the sun is shining. Not to say we ignore these individuals, do the very, very best we can. But frankly, a lot of times there's just not going to be any response from the child to the parent on the part of the parent because the parent's going to go, like you say, to their trusted doctor who may likely not be dialed in in terms of what you and I have discussed today and the value of what we've talked about today. It's incredibly valuable. It is the top tier ahead of any pharmaceutical or other type of intervention.

What we've discussed today are the keys to the kingdom. And it's not monetized. That's why we don't hear about it very much. Yeah. I mentioned alcohol there with my friend's mother. What does chronic alcohol consumption do to that M2M1 balance? Well, the threat of Alzheimer's with respect to alcohol consumption is, a U-shaped curve, that those who do not consume any alcohol have a slightly higher risk in

comparison to women who drink one glass of wine per day or men consuming two glasses of wine today. And then the risk goes up with more alcohol consumption. So there's a U-shaped curve with an ideal range of alcohol consumption. I think more recent literature would indicate that really isn't true globally as it relates to alcohol, that, you know, call it what it is. alcohol is a neurotoxin, and it threatens brain cells. Is there an upside to the polyphenols in red wine? Yeah, there is, but there's also non-alcoholic red wine and other wonderful sources of polyphenols

that don't require alcohol. But I get that, you know, there's an upside to alcohol in terms of what it does for people socially, been part of their culture, but it's not a half a bottle. It's a glass. So, you know, I think it's making these subtle adjustments so that you can still feel good about life and participate and minimize a risk. Yeah. David, one thing we've not talked about is genetic testing. And again, I think a big theme throughout our conversation today is how our approach to medicine has changed over the years, right? There's normal blood test versus optimal. There's getting involved when you have symptoms versus practicing true prevention. And when I was at medical school, Edinburgh Medical School, between 1995 and 2001,

I'm pretty sure we were told about APOE4 testing, but the general view was you don't do it, right? There's no point knowing your genetic status because there's nothing you can do, right? So why would you want to live your entire life with fear when there's nothing you can do? Of course, our understanding has moved on dramatically since then. So I wonder, you know, David, if you could first of all explain, what is APOE4? What does having one or two alleles do to your risk of getting Alzheimer's?

And then I'd love to get your perspective as to whether you're a fan of getting tested or not. Let me first answer that I'm absolutely a fan of being tested. We know that individuals who carry APOE4 alleles. So this is a genetic allele that comes, and you have two shots at it, it comes in three varieties, APOE2, APOE3, and APOE4. As it relates to Alzheimer's, APOE2 is protective, APOE3 is about neutral, and APOE4 is associated with increased risk.

And as I mentioned before, you have two shots at this, so that you can have any combination you can think of between 2, 3, and 4. You can be a 4-4, which poses a significant, it's associated with a significant risk for Alzheimer's disease through multiple pathways that I'll mention just a moment. But it's been indicated that carrying APOE-4-4, and there are a significant number of people in America

who are carriers of APOE-44, that your risk may increase for Alzheimer's by as much as eight-fold, even as high, some reports as high as 12-fold risk, but not determinant. It's a predisposition, but not a determinant. I'll double-click on that in just a moment. Having one allele, in other words, having a 3-4 or a 2-4 combination, is also associated with an increased risk of Alzheimer's by anywhere between 3 and 5-fold. So a really significant increased risk.

Now, why is APOE4 associated with such an increase? What does it do? We know that it involves multiple pathways. It involves downregulation of mitochondrial function and as such seems to target microgle cells. But in work done by a British researcher, Dr. Sarah Marzai at what is called the Marzai Clinic. I had her on my podcast recently. She actually created microgleal cells.

that expressed either no APOE, APOE 2, 3, or 4, and then injected them into the Alzheimer's mouse model brain, who lacked microglial cells, and demonstrated dramatically that those who had APOE2 and had dramatic reduction of inflammation, sort of middle-of-the-road inflammation, APE3, but dramatic increase and cell loss and beta-emoid accumulation in those carrying,

the APOE4 allele, the microglial cells that she had engineered and injected into their brains. So again, while we've kind of labored over what are the exact pathways by which APOE4 is ultimately increasing risk of Alzheimer's, it looks as if now that it's converging on the microgle cells, which is really kind of interesting because we can offer offsets to that through the techniques that you and I have talked about today. what I'm saying is people can have APOE4 allele and then engage these various other lifestyle changes and other practices beyond lifestyle to actually offset and i.e. reduce their risk that would otherwise have been significantly amplified. Again, I want to say that we should look upon carrying the APOE4 allele as not a determinant but as a predisposition. It is clearly a risk marker. it's a risk marker like MTHFR.

Again, 28% of people like me, like I am, have this MTHFR and therefore elevated homocysteine, another risk factor for Alzheimer's. That similarly can be offset in my case by taking methylated B vitamins. So I think there's been a huge change in the messaging of, well, not necessarily with respect to mainstream, but with people who understand that notion

of this APOE4 being a predisposition but not a determinant, that, okay, these are the cards you've been dealt. How are we going to play the hand? Yeah. It's such a key point, David, this idea of knowing your risk. I mean, look at this a different way, right? The amount of times in my career, let's say a middle-aged man would not pay attention to their lifestyle

until they came in for a check and their blood pressure was found to be significant. significantly elevated, right? And often that might happen at a time when maybe their own father had a heart attack or a body of theirs from school, you know, had some angina or something like that. Right? So getting the right test, for some people, yes, it makes them anxious, but for a lot of people, it is the stimulus that they need to then engage with changes, right? So someone might hear this podcast. I go, yeah, yeah, it's important. I look after my brain health. You know, but my life's pretty good.

You know, I don't feel I've got any symptoms yet. My lifestyle is generally okay. If they did a genetic test and came back as a, let's say, a 3-4, maybe they don't have two APOE-4 alleles, maybe they just have one. They then know if they're educated in the correct manner that, oh, okay, if I look at all my risk, I have a genetic predisposition here,

which means it's even more important that I lock in on these lifestyle changes. If I've got APOE44, like double, you know, yeah, you don't want to get anxious about it. You want to go, okay, right, there's nothing I can do about that. What can I do to reduce my risk? And I think that's an empowering message. Now, could one argue, David, that the recommendations that we would make to you for your brain health are the same irrespective. So, for example, if someone was listening

and they said, David, listen, I'm going to get brain defenders and I'm going to do everything in that book. Why should I go to the trouble and expense of getting an APAWI-4 test? Does getting that allele back practically make any difference in terms of what I do? I think the answer is that

I cannot imagine anyone doing everything I talked about in the book. So there's a hierarchy. And I think that if you were carrying APOE4, you would be much more dedicated and really be involving yourself not just in the standard recommendations that I made that people are probably aware of, but I wanted to reinforce, but even some of the leading edge things that we talk about in the book. And beyond that, I think being much more aggressive in terms of following your cognitive function. You know, we have the ability to look at cognitive function in very sensitive ways these days, and that would guide you in terms of at what level should I be engaging

this program that I describe. Yeah. There's so much you've covered in the book day, but we haven't even scratched the surface today. I really appreciate this stuff at the end where you talk about some of these novel therapies, but also where you think this field is going. I also just want to say, I read a lot of health books, and this, I think, is beautifully written. It's very concise. It's to the point as to where the science is, and there's so many practical tips in it that I think people could just pick it up, scan, and immediately know what they have to do. So thank you for once again writing a wonderful book. For that person who has realized throughout this conversation that they've neglected their brain health for the majority of their life, they've not paid attention

to their diets, their exercise, their sleep, their stress. but something shifted within them and they want to make a change but they're worried that it's too late. What would you say to them? If anybody is cognitively intact enough to have that mental conversation, I'm worried that it's too late,

they're in great shape. They are in great shape and ready to take full advantage and redirect their brain's destiny. So absolutely have at it. Yeah, great advice, very empowering. the books called Brain Defenders. Thank you so much for coming back on the show. My absolute pleasure. Thank you. Really hope you enjoyed that conversation. As always, do you have a think about one thing

that you can take away and apply into your own life. But also, have a think about one thing that you can teach to somebody else. This will not only help them. It also helps you learn and retain the information. Now, as this is the last episode of the season, I want to say a heartfelt thank you to all of you who listen each week, and if I may, ask you two quick favors. If you have ever received value from this podcast and have never got round to leaving a review for the show on Apple Podcasts or Spotify, I would really appreciate it if you could take a moment right now to do so. It will only take you about one minute, and it makes a massive difference for the show. Secondly, if there is anyone in your life who you feel would benefit from listening to this episode or this podcast in general, please do spread the words.

My team and I work really hard each week to make this show in order to help people improve their lives. And of course, the more people who listen, the more people who can experience the benefit. So my request is this. Over the summer, can you, would you, share this show. with five people in your life who do not currently listen. If all of you were to do this, I honestly feel we can create a powerful, positive ripple effect where we help more people feel happier and healthier.

No pressure, of course. If you don't want to share for whatever reason, that is completely fine as well. Now, before I sign off, I am really excited to share that I am bringing my Thrive Tour, transform your health and happiness to Canada and Europe this September and November. It's a live, interactive, uplifting show that over 20,000 people came to last year across the UK and Australia. I'll be sharing powerful stories, life-changing insights and simple tools that will inspire you to feel better,

think clearer, and live with more intention and joy. to get your tickets right now and see all of the dates and venues, go to Dr.chatterjee.com forward slash live. I really hope that you can join me. Thank you so much for listening each week. I hope you managed to have a relaxing and nourishing summer, and I will see you back here in September for the new season, and as a little teaser, I have some phenomenal guests lined up already.

Always remember, You are the architect of your own health. Making lifestyle change is always worth it, because when you feel better, you live more.