Transcript for:
Alzheimer's Awareness and Brain Health Insights

I think it's really important that people understand that Alzheimer's itself is the number three cause of death in America. It kills people. The rate of increase of Alzheimer's is far beyond the fact that our population is aging. One would expect that as the population ages, we would see an increase, but the rate of increase far exceeds that. One of the most sought after minds on the planet in the fields of nutrition and brain health, four-time New York Times bestselling author... David Perlmutter. One study demonstrated that there's a profound relationship between the number of sugary beverages and Alzheimer's risk and actual shrinkage of the brain. Really? The reality is that the metabolic defects of the brain begin 20 to 30 years prior to the clinical manifestations. Is it possible to reverse dementia or Alzheimer's with newer mitochondria to create a more present memory functioning? brain? The answer is absolutely. Welcome back everyone at the School of Greatness. Very excited about our guest. We have the inspiring Dr. David Perlmutter in the house. So good to see you, David. Thanks for being here again. Thanks for having me. Very excited about this because there's a massive health crisis in the world, specifically in America. It just seems to be growing and there's a stat, according to the Alzheimer Association, the number of Americans living with Alzheimer's is growing. And growing fast. Nearly 7 million Americans have Alzheimer's and by 2050 the number of people age 65 and older with Alzheimer's may grow to a projected 12.7 million barring the development of medical breakthroughs to prevent or cure Alzheimer's disease. Now you've written six New York Times bestselling books, 15 books in total, you're a neurologist, medical doctor specializing in the diagnosis and treating diseases. of the brain, the spinal cord, and nerves. And I'm curious, what has been, in your opinion, or with the research that you've seen, the biggest cause of this spike in Alzheimer's over the last 20, 30 years? And the fact that it just seems like it's just going to keep growing. What is the main causes of this? And is it bigger in America versus the rest of the world? Or is it equal around the world? Lots of good questions. Let's take a step back. Those statistics are worrisome, they are staggering, and they don't encompass the real issue, which is well beyond that Alzheimer's patient, and that is what does this incredible increase in Alzheimer's do to family members and loved ones and caregivers? What is the economic impact of the loss of brain function of the population in general? And the fact that it the rate of increase of Alzheimer's is far beyond the fact that our population is aging. One would expect that as the population ages we would see an increase but the rate of increase far exceeds that. So we know that there's something operating in the background and the fact that it's changing, i.e. increasing, indicates that it is not genetic. If it were genetic it'd be static. The genes wouldn't suddenly become more prevalent in the population. So we take a step back and ask ourselves, well, what is really going on? Where are we in the understanding of what in the heck is going on? And let's look at health in general, and then we'll focus on Alzheimer's, because general health and Alzheimer's are not disparate issues. The same issues that are affecting the general health of the global population are at play in terms of undermining what's going on in the brain, making a good brain go bad. And it is. In a word, metabolism. Metabolism is the main thing making a brain go bad. That's right. And it's not, it is not, I'll say it maybe three times, the accumulation of this protein called beta amyloid. So what makes up a metabolism for a human being? How cells use energy and the progressive problems with our metabolic health are the number one cause of death. on planet earth. Really? Not COVID, not any other infectious disease, not war. It is the progressive loss of metabolic function that underlies our chronic degenerative conditions like diabetes and various forms of cancer and heart disease and yes, Alzheimer's as well. Before you go on, if you could, we hear the word metabolism a lot. You say, I've got a slow metabolism or his metabolism is really fast or whatever it might be. If I'm hearing the word metabolism for the first time when I'm nine years old or something or 12 years old, could you explain it to me like I'm 12 and say, this is what a metabolism is and here's how it works? As if I've never understood it before, how do you break it down in simple terms? Totally glad that you asked that question. I feel like I scripted you to ask and I'm going to respond to the nine-year-old. Because we all know that our cells are doing things. They're making proteins, they're clearing away waste products, etc. Every cell does something different in the human body, but to carry out any work, we have to have a fuel source and use that fuel to power the engine that allows the cell to do its thing. A car goes nowhere unless it has a battery pack or it uses gasoline. So it's the process of using fuel to carry out the various functions of the cell that we call metabolism. Now, if your car's metabolism is not working well, if for some reason, for example, you mixed your fuel with water or something, then the car is going to sputter and come to a screeching halt because it's metabolically compromised. That's what we're doing to the human brain. We're giving threats to the human brain that are... compromising its ability to use fuel appropriately. Now by and large the fuel is glucose, which is a good thing. Can the brain use fats? Can it use ketones for fuel? Yes it can. So we really need to drill down on what's going on that allows the brain to use glucose and where is the furnace? Where is it burning this glucose to produce energy? And it's doing so. In parts of the cell, organelles that are called mitochondria. So metabolism is connected to mitochondria? To a significant degree, yes. And mitochondria is in the brain? So mitochondria are little tiny organelles that live within the brain cells. Each brain cell may have, even though you see a diagram, here's the mitochondria, here are the ribosomes, here's the nucleus. Typically, a brain cell may have as many as a thousand. mitochondria each cell one cell one cell so how many mitochondria do we have in our brain it's a number that is incalculable so billions trillions billions trillions trillions of mitochondria throughout the human body as well in fact you know virtually every cell in the body does contain mitochondria with the exception for example the red blood cell so the issue then is recognizing the brain is hugely energy Hungry organ using a lot of energy day in and day out. The brain truthfully never rests. When we sleep, the brain isn't going to sleep. It's actually diverting its tasks to cleaning things up and getting ready for the next day. While other parts of your body, your muscles, etc., are resting at night, your heart is resting at night. But that said, the brain is very energy hungry and has such problems with metabolism, how it creates the energy. would be very obvious then in the brain. And it's really the first place to suffer. The reality is that the metabolic defects of the brain that presage to the development of Alzheimer's disease begin 20 to 30 years prior to the clinical manifestations. In other words, the changing in memory, the issues with carrying out purposeful activities, where... Suddenly, now, though the problem began two decades ago when we could have paid attention, now that mom or dad or husband or wife is beginning to have issues remembering the grandchildren's name, the Wi-Fi codes, how to use their iPhone, getting lost, now we take notice and begin to think about, well, what drug can we use now that it's fourth and long? The point I'm trying to make is an important mission is to emphasize that our brain function, our health of the brain, the brain's ability to resist degeneration is dependent upon metabolism. And we need to begin paying attention to that metabolism 20, 30, 40 years prior to when the typical medical intervention is then implemented to deal with a problem. As John Kennedy said, the time to fix a roof is when the sun is shining. So we really need to start getting the word out that our brain depends upon good metabolism. What would you say then are the things that cause someone to hurt their brain or break their brain the most? From, is it emotional? Is it the way they think? Is it what they eat? Is it an environmental thing? Is it, what are the things that hurt a brain the most? Well, anything that threatens the mitochondria then is going to threaten not only how the brain works moment to moment, but set that brain up for a future decay. So if you hurt the mitochondria, that hurts the brain? Yes. So to answer your question, then what hurts the mitochondria? Well, we know that a powerful threat to mitochondria, a direct clear and present danger to mitochondria are certain foods like ultra-processed foods. We know that fructose is a dramatic threat to mitochondrial function. We put a paper out on that topic in February of 2021. Certainly many environmental issues need to be considered. Anything that increases inflammation in the human body increases the threat to the mitochondria and as such. sets the stage for brain decline. So with that understanding then, the idea of developing therapies for people in whom Alzheimer's is now beginning to raise its ugly head, focusing simply on the accumulation of this protein beta amyloid is myopic and has proven ineffective and beyond that has proven threatening. A fascinating A study appeared in the New York Times since yesterday, it was reviewed in the New York Times since yesterday, talking about how the most popular drug that targets this beta amyloid that accumulates in the brain is quite threatening, that about 28% of people given the drug have small brain hemorrhages, but that people who carry a certain genetic predisposition for Alzheimer's are at a significantly increased risk for... these bleeds in their brain. And what the New York Times article reported yesterday is that the company knew it. Wow. And went ahead with the research. Interesting. So, you know, it to me violates the most important doctrine of medicine, above all, do no harm. I mean, all these companies, though, when you, I mean, whenever I watch sports and there's a commercial, I don't really watch much TV, but I do watch sports. Half the commercials are medical, drug-related commercials. And they talk about, you know, fixing one thing, but then causing, I don't know, 30 different side effects that seem pretty extreme, some of these side effects. That's right. We're going to solve one thing, your, I don't know what it is, your eczema or something. Psoriatic arthritis, right. Yeah, yeah, it's like arthritis, eczema, but then it's like, but you might die. You know, it's like the extreme. Let's not say it like that. But it's like dancing people and songs and sunshine. You were distracted by all of those graphics, all the video that's really showing this person now resuming. They're alive, they can wear a bathing suit because their skin is cleared up, and it lowers your risk of, I mean, it increases your risk of infection, including tuberculosis, and in fact, you may even die. You're right. But you're looking at this person who could finally take off his shirt, and, you know, it looks great to me. But how do these medical companies get away with it if their whole mission is to do no harm? I understand that the intention is we're going to try to solve one problem. The eczema, the heart palpitations, whatever it might be, I don't know, all these different things. But if you're solving or helping, and it really doesn't fix one thing, it seems like it helps one thing, but if it hurts you and a lot of other things, isn't that doing harm? Lewis, that it may, respectfully, may not be the mission. I mean, I think oftentimes what we see is more interest in shareholders than stakeholders, basically that, you know, focus on the bottom line. And with the, there was a resounding rejection of the approval process of a certain Alzheimer's, so-called Alzheimer's drug called Lekembe, still being, you know, editorials are written, why was this drug approved? Because its clinical effectiveness after 18 months is minimal at best, and the side effect profile is very scary. So as we look at the risk-benefit ratio, it doesn't add up. You mentioned processed foods, fructose, things that cause inflammation in the body. You know, obesity is one of the main, I guess, is something that's happening. I don't know what it is, 30 or 40% of America is kind of obese now or is that what the calculation is? I'd say it's close to 70 to 80% are either overweight or obese. Really? In fact, north of 90% of Americans have at least one component of metabolic dysfunction. And obesity is a- Obesity, overweight, obesity is one of them. Certainly hypertension, elevated blood sugar, insulin resistance. These are all things that we consider. I add elevated uric acid to the equation as well. This lipidemia or problems, abnormal lab studies as relates to our blood lipids. But having said that, only one or less than one in ten individuals is metabolically intact in America today. it's these metabolic issues that set the stage for all the things we don't want to get, including Alzheimer's disease. And so, you know, a lot of these weight loss drugs are taking off because they have been effective in losing the weight, it seems like, for some people. And I haven't studied this enough to know the side effects or the harms of those. But you see cases of people losing a lot of weight quickly, it seems like. What is more harmful, and maybe we don't have the research yet, but what is more harmful, being obese to our brain health? Or using a drug like an ozempic to lose the inflammation on our body and the excess weight, but is there side effects that are causing more harm to the brain long term than the obesity? You mean of using the drug? Yeah, like losing the weight but staying on the drug or having obesity and not being on the drug. What is more harmful to the brain health? So I'm going to challenge you a little bit here. Okay. And because it challenged me quite a bit as well. So, you know, obesity is not just an accumulation of body fat. There's a lot going on with obesity in terms of letting us understand that metabolism is really in disarray. Obesity is really kind of the outward manifestation of what I call metabolic mayhem. There's a lot going on with obesity beyond just the presence of body fat. We know that mitochondria are a threat. And we know that. Inflammation markers are skyrocketing. We know that there's an increased leakiness of the bowel. We know that risk for neurodegenerative conditions is going up. Diabetes, of course. So it all dates back to or gets back to the issue with metabolic and the threat that is evident when someone is obese or hypertensive or has elevated blood sugar because they are insulin resistant. It's an indication that their metabolism Dr. Is dysfunctional, that is a clear and present danger to the brain. So what happens if you take one of these GLP-1 agonist drugs like semaglutide, like Ozempic or liraglutide and lose the weight? What's happening? Is that a good thing or is it a bad thing? That's what your question is, isn't it? Dr. Yes. Dr. And you're expecting a particular answer from you. Dr. I'm not expecting any answer. I'm curious your response. Dr. And I think you're going to be surprised by where we go with this because I'm not going to be surprised. What these drugs have been shown to do is nothing short of remarkable in terms of metabolism. So they were originally developed to help people lower their blood sugar, to improve the way we're able to control our blood sugar, and it was almost as a side effect initially that people noticed that their weight was going down. And now, of course, they've been repurposed and subsequently approved. For weight loss, but there is a lot going on with metabolism as a consequence of GLP agonist drug. In a good way or a bad way? In a good way. Okay. And I am not, you know, generally my mission in life is not pharmacocentric. You know, I want to allow people, and we're going to morph back to that in just a moment, but the reason we're going to unpack this GLP-1 agonist drug and why it's having positive effects in the brain. Dr. Is because it will subsequently again allow us to circle back to the primacy of metabolic issues as it relates to brain health. Here's a powerful validation. So the GLP-1 drugs do far more than help us control our blood sugar and lose weight. They focus on metabolism. They actually enhance mitochondrial function. Really? Dr. Can you believe it? I mean the… Most of the work has been done in diabetic patients, but showing reduced free radical formation, increased oxygen consumption, in other words, an improvement in mitochondrial function, which requires oxygen for the burning of the fuel, and various other metabolic markers that are improved in diabetic patients who have been prescribed these modifications. In the New England Journal of Medicine in the spring of this year. Well, let me go back a little bit. So, Alzheimer's, as I've indicated, is primarily a metabolic issue. It's a mitochondrial issue. You fix the mitochondria, you fix the brain health. Yes, and if you damage the mitochondria, you set the stage for Alzheimer's. You set the stage for neurons to undergo suicide. Dr. Go back if you've hurt the mitochondria so much for so long, is there a way to reverse it? Absolutely. Dr. There is? Yes. There's a lot we're going to have to do. Dr. We'll do this maybe in the fourth hour. To sidetrack on that answer real quick, I will say that yes, we have a huge opportunity to replace defective mitochondria with fully functioning, better functioning mitochondria. We do that through scavenging dysfunctional mitochondria through a process called mitophagy, and we can grow new mitochondria through mitochondrial biogenesis, and we'll talk about how we can make that happen. But therapy for the brain and improvement in Alzheimer's patients, or at least slowing their decline, and Parkinson's as well, focuses on dealing with the dysfunction of the mitochondria. That's where we need to be in This epidemic that you opened our discussion with today. So, I do want to tease the audience a little bit with the notion that we've always focused on the brain cell. One would think that's where the action is, the neuron. Because it's so active from an energy perspective, i.e. the mitochondria. I indicated earlier that a neuron may have as many as a thousand mitochondria. But it turns out where we are... In the latest research is really exciting because it's shining the spotlight not on the neuron itself but on the caretakers of the neuron. We're going upstream of the neuron. The neurons are worker bee doing what it can do. Hopefully the environments going to be one that is salubrious in terms of how the neuron does what it needs to do. Transmit information, connect to another neuron through a synapse, and allow the networks to function. But the care The caretakers of the neurons are the brain's immune cells called the microglia. So these microglia make up about 10 to 12 percent of all the cells in the brain. And they are immune cells. They're part of the innate immune system, but they do a heck of a lot more. So when you think of immune cells, you think of, well, you know, how it's able to fight off bacteria, viruses, fungi, etc., how it protects us. We think of immunity in terms of our body's ability to take care of these confrontations. People are interested in a robust immune-ish function. Now that COVID has, you know, let us recognize that those individuals whose immune systems are not up to snuff were and remain at higher risk for complications from COVID and even long COVID. Who are those individuals? These are individuals with diabetes. Obesity, hypertension, three of the big players in metabolic diseases. So what I'm saying then is there's this powerful then relationship between our metabolic health and our immune health. To the extent that there's now been defined an area of medicine called immunometabolism. Immunometabolism. In my area of interest, the immunometabolism conversation takes us to the brain's immune cells called the microglia. The microglia are wholly dependent upon their mitochondrial energy producing function. The ability of the mitochondria in these microglia to do their job and allow the microglia to nurture our brain cells, to nurture our synapses. To create chemicals that allow us to grow new brain cells and to shore up what is called the blood-brain barrier is fully dependent upon their metabolism, their mitochondrial function. When mitochondrial function is threatened, these wonderful, loving, nurturing cells shift to become the evil twin. The same cell now destroys our neurons, activates pathways in neurons to undergo apoptosis or pre-programmed cell death. It threatens and damages and destroys ultimately the synapses where communication takes place. It reduces the formation of this chemical to grow new brain cells. It increases the production of beta amyloid and ultimately threatens the integrity of the blood-brain barrier. Same cell, two types. The nurturing... M2 phenotype and the evil twin, the M1 phenotype. And the microglia can go back and forth, and their ability to go back and forth, and what motivates them to change from being the helpful twin to the evil twin, are changes in their mitochondrial function. And it is reversible. Really? So we can go back to a wonderful, nurturing brain that allows more synapses to form, that allows new brain cells to generate in the brain. Who wouldn't want that, especially in the brain's memory center, and really creates an environment that's nurturing for you, our brain. But is it possible if dementia has gone too far into Alzheimer's and... Is it possible to reverse that dementia or Alzheimer's with newer mitochondria to create a more present memory functioning brain? The answer is absolutely. Really? Yes. Even if it's like they've had dementia for a decade or five, ten years or Alzheimer's for a while? Well, the duration of the issue is less important as how aggressive it is. as one would expect, as one would see with other degenerative conditions or even cancer, some people get attacked more aggressively and decline more quickly based upon their metabolic health and others don't. So can it be reversed? Yes. Are there new studies demonstrating that targeting metabolism has a dramatic effect on the brain in an existing Alzheimer's patient? Yes. And this gets back to our GLP-1 agonist story. Interesting. Okay. And so you're saying you're seeing that the GLP-1 drugs are having a huge benefit to mitochondria health, which has a huge benefit to brain health. Yes. So let me, let me run through the dots because this will be on the quiz. Why we want to, why we want to target metabolism, why the GLP-1 drugs have such an opportunity to Be game changers. And again, you know, my focus has never been medication, but my commitment has been to never take anything off the table. Under the doctrine of above all, do no harm and looking at things like risk benefit ratio. What I'm saying is that metabolism is the central focus. This is one avenue that seems to target metabolism and does so aggressively. Long-term, how might that play out? We don't know yet, but. A poster presentation that was at the American, rather the Alzheimer's Association International Conference about two and a half months ago revealed a one-year study in which the actual Alzheimer's patients over a one-year period compared to control, their rate of brain shrinkage receiving a GLP-1 agonist drug was reduced by 50%. the rate of shrinkage of their brain. Their cognitive decline was dramatically reduced in comparison to control. Published in the New England Journal of Medicine in, I believe, March of this year, was a three-year study giving a GLP-1 agonist drug to patients who already had Parkinson's disease, a disease for which we have no treatment whatsoever. Some of your viewers are going to raise their eyebrows saying, well, I know of drugs that treat Parkinson's, and I, as a neurologist, have treated patients with drugs for 30 years. But they didn't solve something. They just kind of minimized something, right? Exactly. These are symptomatic. This is symptomatic management. And I'm not derogating it. I mean, there's really a very important benefit to patients to reducing their tremor, to improving. their ability to walk and reducing their rigidity. That's for sure. Any Parkinson's patient or family member right now watching this will recognize that the drugs that their mother or father may be taking are really designed to treat symptoms, which I think is very valuable, but we're treating the smoke, but not the fire. Treat the smoke. That's important. The root cause. Let's look at the fire. There's a 41% increased risk of Parkinson's in... Diabetics, a metabolic challenge. Oh man. Because of that, a study was undertaken to determine, well, if we treat Parkinson's patients with a diabetes drug, in this case a GLP-1 agonist drug, how might that affect their time course? So Parkinson's patients are rated on a functionality score. Called the Unified Parkinson's Disease Rating Scale. Kind of a common way that we look at Parkinson's patients over time. How quickly are you deteriorating? We expect over a three-year period to be a moderate decline in functionality, and in the control group of this study, indeed, there was a decline, a worsening, a higher number on that scale. The patients treated with the GLP-1 ozempic-like drug not only stabilized in terms of that scale, but had a small improvement. Really? Can you imagine? I've never seen that before, but that is finally treating the fire. Wow. That's big. Yeah, and it's a game changer. Now with every, I mean, I'm open to all possibilities. And if you're saying it's a game changer, I believe it. If the research is saying it, I believe it. But I also know that with every, you know, drug that's treating something, there has to be some side effect also. There has to be something that is shifting things in certain ways chemically that could also cause harm. Potentially. I don't know what that is, but I'm assuming there's something out there. I completely agree. Now, if I had Alzheimer's or someone had Alzheimer's in my family and I was like, this is good to reverse it, it might be worth the side effects to be like, hey, I'm clearer, I'm sharper, I'm like able to remember people's names. It may be life changing. Yes. So you as a consumer or the caregiver of that individual should be given information to Look at that metric, that risk-benefit ratio. What are the downsides and what are the potential upsides? As related to the Parkinson's interventional trial, about 40% of the people receiving the drug had pretty significant gastrointestinal issues. Interesting. What does that mean? Nausea, vomiting, diarrhea, etc. They lost weight though and they had better memory function? They had better memory, no. Better brain function? Wasn't even looked at. What they had was. was it did not decline in terms of their ability to carry out what are called activities of daily living, self-care, mobility, the things that decline in the parking situation. Did it improve a little bit or did it stay the same? It didn't decline. It actually, if I just finished making a slide, it actually improved a tiny bit. Wow. Like a percent or two? Less than one percent. Okay. But look. That's better than declining every day. Yeah. But even a reduction in the rate of decline would have been game-changing. That's what was observed in the Alzheimer's patients, that their rate of decline, they continue to decline, but their rate of decline was markedly reduced, far more so than in the drugs that have become FDA approved that target beta amyloid. Well, what was the stat you said? Was it 40% of diabetics or diabetics had a 40% chance of... Increased risk of Parkinson's. Increased risk of Parkinson's. Yes. And how many people in America are diabetic or pre-diabetic right now? That number is probably around 75%. Wow. Is that diabetic or pre-diabetic? What is the difference between pre and diabetic? Really, it depends on the blood sugar measurement, where the cutoff is specifically for diabetes, which is a marker not only measures blood sugar, but also looks at something called the hemoglobin A1c. So 70% of Americans are pre or diabetic. Pre-diabetic. or diabetic and i think that it's unfortunate that we use that terminology because we get to the discussion of you know when you go to the doctor and look at your blood sugar or look at yourself if you have a continuous glucose monitor you know what your blood sugar is and you're going to ask yourself well what's normal and i think um in healthcare we've been looking at what's so-called normal range what's in the normal range for a long time and i think that's uh doesn't really serve the notion of optimal health very well. Right. Normal may not be healthy still. Normal is what's common, basically. You take a large number of people, you see what is normal. You know, what is, our population isn't normal. Our population, as we discussed earlier, is not healthy. We should define what is optimal. And so, you know, typically a doctor would say, well, your blood sugar is 100 or 105 and everything's fine. We'll see you next year and check again. a very static measurement of your blood sugar fasting that you'll probably train for a little bit so you can get a good number. And I really want to know what is your worst blood sugar? What is the level of blood sugar at its worst and how long does it stay elevated after carbohydrate challenge? What is, as we talked about off camera, what is over time the area under the curve? In other words, when we look at the level of blood sugar over time, it defines an area. And that's really a very valuable metric in terms of understanding the dynamics of blood sugar and how insulin is working in your body. Which is one of the fundamentals for medical health. Wow. Because the brain, by and large, powers itself with glucose. The higher the glucose over time, the less the brain is able to use it because many parts of the brain depend upon insulin to allow the glucose to be used as fuel. As we threaten the function of insulin, by virtue of the fact that our blood sugar remains elevated over time, We threaten the brain. We threaten the mitochondria. We get back to the change between the good and the bad microglia, and that threatens neurons. I was at a summit recently where there was a panel on longevity with Dr. Rhonda Patrick, Peter Diamandis, and Dr. Walter Longo. I think you know all three of them, I'm assuming. And Walter Longo was talking about The fasting window research has shifted in the last year. I'm not sure if this is 100% accurate what he said from my memory, but he said something like, you know, we used to think it was 16-hour, you know, fasting, 8-hour eating windows, feeding windows, but the research is showing more of a 12-hour fasting window, unless you're doing like a 24-hour or two-day fast or something, but more of a 12-hour window. He's saying the research is showing more of that now. I don't know if that's 100%. Dr. What he was talking about or something that was shifted there? Dr. Well, I think that what he's saying is that there's more research coming out indicating that the period of fasting doesn't need to be as great. I would say that this is really more of a discussion of what is called time-restricted eating as opposed to specifically fasting. Those are kind of a bit nebulous terms. When you say time-restricted eating, well how much time? When you say fasting, is it three days? Is it 12 hours? And I think it's kind of an analog scale. That probably 16 to 18 hours is going to be better than 12 hours, but there's benefit to a 12-hour fast. And that is, or at least restricting your consumption of calories or other types or other parameters as it relates to food, anything but water. There's been a discussion, well, is the morning coffee, even if it's black, did you break your fast? Coffee lovers like to say, no, you didn't break it. No, nothing. I'm still on the clock. Yeah, yeah. But that said, this remains in evolution and I think that there's more to come. And it's really quite exciting that we have researchers like Valter Longo who are looking at the implications of these types of interventions which are fairly simple to employ, not only as it relates to longevity parameters. but also in his work as it relates to even the immune system vis-a-vis cancer. So we're learning a lot that immunometabolism relates not only to these chronic metabolic diseases, Alzheimer's, but the function of the immune system as it relates to its ability to seek out and destroy cancer cells, for example. So I want to go back to the GLP-1 drugs because, again, I haven't heard someone clearly define beyond weight loss the power of these drugs for brain health and like I'm hearing you say now based on the research right so I'm happy to hear that and I'm happy to hear that people who have dementia or family members of dementia or Alzheimer's now have some type of hope hopefully that they can start testing this for themselves to see either A reduce in decline or a potential increase in cognitive function, right? Well, let me take a step back then, Louis, if I could, because let's ask ourselves, how did we get to the GLP-1 discussion in the first place? Right. And is there a way to prevent even getting there, needing these things? Yeah, and it was through the lens of wanting to really unpack the fundamental role of metabolism in brain health. Yes, which metabolism is linked to mitochondria health, right? Mitochondrial health. And I use the GLP-1 drugs as a way of really kind of supporting the notion that it's all about metabolic health. Because these results are, for me, being at this for quite some time, I use the word astounding because they are. It is really the first time we're targeting the fire and not just the smoke. But it sounds like if we just target the fire on a daily basis, 10, 20, 30 years beforehand and do our best to not put ourselves in a situation of pre-diabetic, diabetes, obesity, inflammation, eating processed foods, having a lot of high blood sugar spikes continually throughout the day. That is treating the fire by preventing the fire, correct? Yeah. What a notion. I mean, people don't talk about it. But Alzheimer's prevention, I mean we are led to believe, to get back to the various commercials that you watch when you're watching the evening news, pretty much, and look at the people in those commercials. Just look at the actors and who they are designed to target. So we're kind of led to believe that we should live our lives however we want, come what may, and that modern medical science will fix our ails. Yeah, there's no one with a six-pack and like... shredded on these commercials or just super, you know, healthy looking like a little bit overweight or really? Yeah. And and I'm not being disparaging. I'm simply saying this is a marketing ploy. But again, I want to get to the belief part of it that we believe that, hey, you know, modern science is going to fix my fill in the blank, take a drug and it's my my ozempic for my obesity, my Alzheimer's. Now that we've heard this new, exciting research. So what the heck? Why should I worry? I'm going to do whatever I want, eat whatever I want. Stay up late, I don't really like to exercise, do all the things that feel good. You know, truthfully, they're called comfort foods for a reason, because we all love them. They taste great. Our brains are programmed to seek out sweet and fat and salt. And these are things that threaten metabolic health. As it relates to fat, we know there are good fats and bad fats. But by and large, we're programmed to seek out foods that are fatty. Why? Because they're calorie dense. They are a survival mechanism that allows... causes us to seek them out. Sweet, what does it mean? It means that food is ripe. It means it is safe. And when does fruit ripen? It ripens at the end of the summer and the early fall as a clue to our physiology to make our body make more fat to allow us to survive winter, a time of caloric scarcity when we were hunter-gatherers. So we are deeply programmed to love sweet. When I lecture, I say, and I ask the audience, how many of you think you have a sweet tooth? Don't raise your hands. Answer is every one of you. We do. We all have a sweet tooth. But these are deeply seated mechanisms that did us good, allowed us to survive so we could have a conversation today. The issue, though, is that when we gravitate now to those foods in excess, there's hell to pay. There's a downside, and that's what is leading to these metabolic challenges that are really quite central to not only... What you described at the opening of our time together, you know, these incredible rates of increase of neurodegenerative conditions well beyond Alzheimer's, but the other metabolic conditions as well. Rates of diabetes soaring well beyond what was predicted in 1990. Obesity becoming a global problem, you know. As the global diet has, we used to say, people adopt the American diet, it became then the Western diet, faces now the global diet. Even in the Mediterranean, we talk about the Mediterranean diet, people around the Mediterranean basin are eating this same stuff. They're getting bigger, right? They're getting bigger. They're getting diabetes at ever-increasing rates, happening globally. Even in all the blue zones, you hear about, you know, the blue zone in Japan, it's like it's not becoming a blue zone anymore because there's so many fast food restaurants. The conveniences around those places seem to be excessive. And people... Naturally lean into convenience over discipline when it comes to food and decision-making unless, I don't know, they're just so disciplined. Why is it so hard for human beings to go against temptation and conveniences to stay healthy? I'm going to give you the short answer and then I'm going to unpack it. Yes. It's because of the food they eat in the first place. The very first... foods that we are eating are rewiring our brains away from making better decisions. And causing us to want more of it. Yes. So let me simplify. We may have touched upon this before. I think we did a couple of years ago. And that is that let's say we have two main decision-making parts of our brain, the five-year-old and the adult in the room. The five-year-old, the amygdala, I want the cake. now. I'm staying up late. I'm not doing my homework. I deserve it. All the things. The adult says, you know, this is what you should be eating. And I think you need to go to bed now. And, you know, these are your instructions. This is what is good for you in the long run. That's the prefrontal cortex. So we have these two important decision-making parts of the brain that influence. What we ultimately do, the amygdala, the short-term gratification part of the brain. That's in the front? Dr. Which is the short-term gratification and then the prefrontal cortex, the adult in the room. When the amygdala is in charge, we think only of ourselves, we don't think of other people. We think of immediate gratification, we do not think of long-term consequences. And that's in the back of the… Dr. It's inside… Got you, okay, got you. Dr. So… So… What happens as we mature is that with time we establish a connection, a better connection, whereby the adult in the room can be more influential. So these areas are interacting. And we call this top-down control, where the adult says to the amygdala, yeah, I know you want to do what you want to do, but here's what you should do and here's why. So you're able to recruit all of this wonderful information that is now... part of your experience base, and explains to your decision-making process why you don't want to eat what you think you want to eat. As an expert in this field, someone leading the research and been doing this for many decades, where's the biggest challenge you face personally, where you might lean into something that you know is bad for you? Even if it's like a little thing here and there, what's the temptation that you lean into? Is there food? Is there... Something you do that you eat a certain way sometimes or drink something, whatever it might be, that you're like, I know this isn't going to help my future brain health, but I do it anyways. Well, I'm a lot older than you, so I've had to tighten up quite a bit. Really? Oh, of course. I mean, you know, I think you asked me last time if I could have my 30-year-old self inform me. I think the answer was stay out of the sun as much as I did and floss my teeth more often. But having said that, what are my biggest challenges, I think? And I don't really labor over sweets. I think I could drink less. I think that, you know, I've been saying one to two glasses of wine a day, and I might have more. And I have to admit that I should be more probably disciplined in that regard, but I don't mind how I feel. And so. Well, there's a lot of negative effects with alcohol to the brain, right? There are. There's no benefit to brain health. There's no benefit to brain health chemically. But as my son pointed out on a podcast to me, he said, there may be a benefit to the socialization that then happens when you're with people and you have that third glass of wine, which I'm guilty of. Sure, sure, sure. But it doesn't help mitochondria. It doesn't help mitochondria. No, it doesn't. And so you have to kind of... Do everything else to, I guess, benefit the mitochondria and kind of minimize that potential risk, right? Yeah. And I would say that on occasion I stay up too late. When I get to a place of being deeply involved in research, I can't turn it off. Yeah, it's hard. I cannot turn it off. And I know I should go to bed. And my wife tells me I need to go to bed because she is... Remember, you just said this on a podcast. Yeah, it's like... I know, but sometimes I'm so close to discovering something and pulling things in, I just can't lose the thread. What are the negative side effects to brain health and to the mitochondria or to metabolism when you get five to six hours of sleep versus seven to eight hours of sleep? Is there a big difference to brain health? Well, I think... That tends to generalize. We do know that there are some individuals who are able to sleep five to six hours and do quite well. And again, there's no magic of the eight hours. We know that Alzheimer's risk is increased in people who have shorter duration of sleep and who have longer duration of sleep as well. That once we get north of nine hours of sleep, Alzheimer's risk goes back up. So it's a bit of a U-shaped curve. But I think that what the data, what Matthew Walker has talked about in his really wonderful book Why We Sleep, is there are a variety of issues. One thing that we see when we don't sleep enough that I think is really fundamental is that inflammatory chemicals, cytokines, seem to increase. The very next morning we've lit up the amygdala, the impulsive fear-mongering part of the brain, the child in the room, the poor decision maker. And as such, our decision-making is threatened dramatically. Wow. Such that when you look at the type of food choices a person will make when he or she is deprived of sleep for a night, it's dramatic. The caloric consumption that happens and the quality of the food that people will consume and even other measurements of decision-making quality in studies, which are correlated, interestingly, with functional MRI evaluation of the activity of their brain's amygdala, the fear center, the poor decision maker. So that's something people don't really talk about. I mean, what people are really talking about these days is the activation in the brain. And this is important. I don't mean to minimize it. of basically the ability of the brain to clear itself out. You know, the brain has a lymphatic system as well called the glymphatic system. And it's during sleep, during deep sleep, that our brains are able to rid themselves of accumulated things that happen during the course of the day or through our exposure. So that's certainly very important. So, you know, the other thing that happens, I think that's really very relevant, gets back to dead center to our conversation, is... with repeated lack of restorative sleep, it's a powerful threat to metabolism and mitochondrial function. And this then causes obesity, inflammation, and directly threatens the mitochondria and therefore allows us to understand why people who chronically don't get enough quality sleep, i.e. length and quality are important, are at a significantly increased risk for Alzheimer's. Risky is it to have a night job and to be off on the natural, I guess, circadian rhythm of when the sun comes up and goes down? Significant. And, you know, it is what the science is saying and it is something that night shift workers need to be aware of. I mean, by and large, they don't get as much sleep if you were to measure the quantity. As people who have a daytime job, number one. Number two. And probably not on quality either, right? It's not as good luck getting your room to be dark and quiet during the day, especially if you live in a city. So they're at significant increase for a variety of issues, including neurocognitive decline and including various forms of cancer. So it's anything but ideal. Wow. There's something, I don't know if you have the information to be able to comment on this, but there's something I saw about a month ago. online and it was talking about the negative side effects of kind of like Botox and fillers and things like that in men and women. Is there any research around excessive use or even just normal use of Botox fillers or other things that cosmetic injections that directly link to either brain health or gut-brain connection or mitochondria or metabolism health? Because There was a video I saw that talked about how, you know, if you're getting fillers in your face, it's not really draining out. It's kind of just migrating in different places around the head. And I'm wondering, is that entering the brain in any way? I don't have no clue if it does or not. Well, these are very separate issues. First, let's talk about Botox. There is evidence that this botulinum toxin is able to migrate down nerve pathways and may in fact make its way Into the brain. Really? Well, that's been well described. And that's a toxin. So when a toxin that goes in the face somehow goes through the blood barrier into the brain, what does that do into the brain? Unclear. We don't have the research yet. The notion of that happening, I think, a toxin is something that we should be considering. Now, gosh, I was, I think, the second person. Neurologist in Florida to undergo botulinum, Botox training and I was using... Really? Yeah, so I was using Botox not for a cosmetic reason but to treat people who had various types of facial spasms, neck spasms, eye closures, etc. To relax the space? Yeah, people would have what's called blepharospasm where the eye would close and we could inject the orbicularis oculus muscle so that their eye would relax a little bit. And it was very helpful and inject... when they had spasmodic torticollis and their neck would turn, we would inject the cernicotomastoid muscle and they would get benefit for a period of a couple of months. When was this when you got trained? Gosh, this must have been at least 25 years ago. But then it started being used for cosmetic reasons. Oh, it was already being used for cosmetic reasons in my office because in those days, the many members of my office staff would Notice if I had any Botox left over after I treated a patient. Do a little on their forehead. I would, I have to admit. But having said that, I think we have to watch this data. And I think that the scientific community, medical community, is well aware of that as a potential risk. Really? As it relates to fillers, I think the biggest issue would be that this is a foreign chemical put in the body by and large. Some of the collagen-based injections are really not that foreign, but I think what you can see are allergic reactions. And whenever there's an allergic reaction, it's amping up the immune system. Creating inflammatory chemicals, what that does in the long term may not be good. Do we have the research yet in the last 20 years of kind of what happens to the immune system, to the metabolism, to the brain function with fillers, Botox? I think it's an interesting area to explore. I'm not sure even that, you know, I can't quote you research that's ongoing as it relates to that. But I think it's interesting. Interesting. I just worry about any type of drug, toxin, injections that people do excessively, you know, if there's some other way to prevent or optimize, I guess, without injection of toxins. You know what I mean? Well, Lewis, let me... Like, I guess there's a difference between like a peptide versus like collagen versus toxins, right? And it's like, okay, where do you, I guess, go with all this? Well, here's where I'm going to go with it. And that is it doesn't need to be injected. So that opens the door to topicals and the risk of toxicity in the human body from what we are exposing ourselves to with anything that's put on topically. Whether we think we're doing the right thing by using sunscreen or moisturizers. This is well beyond the notion of hair dye and all of that type of stuff. You know, clearly represented a danger. In fact... How dangerous is hair dye? Well, originally, the original work on hair dye was done by Dr. Bruce Ames. So Dr. Ames, decades ago, was able to identify certain chemicals in hair dyes that were carcinogenic and developed a bacterial test using a type of bacteria, I think it was streptococcal, that could be used globally. to evaluate various chemicals in terms of their carcinogenicity. Could they cause cancer? And so he was able to identify certain components of hair dye that were indeed quite threatening. Really? Yes. Are there innovative hair dyes that are less threatening, that are more organic or natural in nature? The question then arises in terms of have they been thoroughly vetted? And that is worrisome because most of these products Haven't really undergone rigorous human trials or even animal trials that are still sold in stores that may well be threatening. There's really no review process for these products. When you dye your hair, what is happening? I mean, is the hair dead? Is it like a dead cell? Is it still connected to living cells? Well, hair is dead. Hair is not living. So if you dye it though, is it entering through the cells? From that chemical? It's entering through the skin, your scalp. But interestingly, the part of the system that is alive is of course the cells in the skin that manufacture and color your hair. So the cells, the melanocytes that are involved in giving your hair color decline in function over time as their mitochondria begin to fail. Really? So as their mitochondria begin to fail, they're less able to create the color of your hair and your hair turns gray. So the more you color your hair, you're weakening the mitochondria. No, no, I didn't say that. Okay. What I'm saying is the more these cells that are involved in keeping your hair colored are declining in terms of their functionality, the less able they are to impart color into the hair and your hair turns gray. And that's your total health, that's your environment, the foods you're eating, your sleep. To some degree, there's certainly a lot of heredity involved in it as well. But these cells become what's called senescent, which means they lose their ability to divide, they lose their ability to function. And the fact that they are senescent oftentimes allows them to create certain chemicals that causes the next cell adjacent to them to also become senescent and less functional. It's why You know people develop a patch of gray hair in certain areas and it tends to spread. Yeah I've got a little bit a little bit here. I got it. I got a how do you can you reverse gray hair? It's a good question. I've wondered and this is not a pitch but I've wondered if either NAD or urolithin might help reverse gray hair. NAD. NAD perhaps. We don't have NAD per se but NAD. NMN or NR, nicotinamide mononucleotide or nicotinamide riboside, the precursors for NAD in the human body. I wonder if that or perhaps urolithin A may contribute to less... Lessening of gray hair. We don't have the research on this yet? I've not seen it, but I've experienced it. You've taken this and you've seen like a reversal or just a stop? Suddenly over here, all growing black hair. Come on! Yeah, and I pointed out to my wife, I said, you know, I'm not using just for men. What is that stuff? Yeah, you're not dying your hair? I'm getting these black hairs or dark hairs. Really? So who knows? Interesting. But I think that if you target mitochondrial function, there are so many things that we could be talking about. That might happen. I don't know for sure. But next time I come on your show... Let me know if you have all black hair over here. I'll be like, yeah. Just for men. So what is the research around people that dye their hair continuously or a couple times a year? Is there research around how it impacts mitochondria, metabolism, brain health? It's tough to say because there are, you know, how many types of hair dye that are out there. So that's not a... That's not how science works. Science works at one variable, generally assessing one variable that's now being challenged, which I'm grateful for. So it might be one hair dye or, more importantly, one chemical in a hair dye. Let's see what that does over a period of time in laboratory animals and then perhaps in an interventional trial. Okay. So if someone… We've covered a lot of water fun. I know. This is good, though. If someone dyes their hair, I guess you don't have the answer to this, but if someone dyes their hair with… Over-the-counter normal hair dye, I guess. Are they hurting the functionality of their hair quality, strengths, and color by doing that? Or is it not hurting that in the research that we have so far? Hard to say because inherent in the ability to dye hair is first stripping it and allowing so that the dye then is more able to penetrate the hair. Is that necessarily good for hair? I tend to think that it is not. Got it. Okay. So, you know, we've gone from inside the head to outside the head. Yeah, well, I don't know how it's impacting. I'm just curious. Yet it's exceedingly common. Did you used to dye your hair ever? Never have. Never have? No. Not even a little, like, just for man on the sides or something? Never went with it. You know, I'm okay with it. I'm just fine with it. Yeah, yeah. There was a clip that we posted the last time we had you on that went crazy on Facebook. My team told me that it was our most watched clip on all of our Facebook videos from you. And I wanted to follow up and see if there's more research from what we talked about. And the clip that we talked about that went crazy online was around... The pros and cons of having a vaginal birth for mothers versus a cesarean c-section for mothers. And you mentioned something about kind of the pros and cons of the immune health of the child, however they're being birthed. And I don't know if you remember this. Oh, I do. And if you can elaborate on... The pros and cons of a c-section versus a vaginal birth and I understand there's certain complications these days for women needing to have a c-section for whatever reason but is there research on the pros and cons of vaginal versus cesarean section births and if someone has to do a c-section for whatever complicational reasons is there a way that you can still benefit the child so that they get the Optimal immune capacity from that birth. Yes. So, does the child enter the world through the vagina or through an incision in the mother's belly, basically, a cesarean section? And those are very different experiences for that newborn. We have to recognize that a cesarean section is a life-saving, wonderful... procedure now done in a hospital sterile environment such that, quasi sterile environment, we'll get to that in just a moment, such that a child can be saved and mother can be saved as well if in fact this pregnancy is threatening to mother. So there's a time and a place that's for sure. As we sit here right now, about 30% of births in America is delivered via a C-section, which is an exceedingly high number. What was that 30 years ago? It's been pretty consistent over the past 30 years. And I'm going to say that some of the reason it happens with All due respect, it's not because there's a threat in terms of the newborn or the fetus rather or mother's health but because of convenience. I think to be fair to mothers and fathers, parents to be, that a full explanation as to potential downside risks of a C-section aside from a scar or any other complication to the mother in terms of a general anesthetic and surgery and an antibiotic being administered. I should include what are now the well understood risks to that newborn and here is what they are. When a child passes through the birth canal in a normal vaginal delivery that child is anointed, anointed with these seeds, the bacterial seeds, the viral seeds of his or her future microbiome. The bacteria, the viruses, the other organisms that invest that child and determine various functions of that child when he's an adult or she's an adult. Really? The set point of immune reactivity, for example. That the immune system receives a significant degree of programming from the gut bacteria. And the differences in the bacteria in the gut between a C-section born child and a vaginally. delivered child are significant. We know that changes in the array, the functionality, and diversity of the gut organisms relate to things like diabetes, obesity, and even risk for autoimmune conditions. Having said that, what the science reveals is there's a pretty significant increased risk of autoimmune conditions in children born by cesarean section. There's a dramatic... increased risk of autism, ADHD, and autoimmune conditions like celiac disease and type 1 diabetes in C-section born children as opposed to children born vaginally. And the research is out there on this? Research has been published for at least 15 years. Now, are there other things that happen in terms of physical compression of that child at the time it passes through a... A tight canal versus being just liberated in the C-section, perhaps it's playing a role, but I think much of the research, most of it, is focused on the anointing of that child with a specific type of bacterial array, viral array, in the birth canal that invests that child's eyes, ears, nose, mouth especially, and then serves as the seed for his or her upcoming gut microbiome. As opposed to forming that gut microbiome based upon whatever bacteria happens to be on the surgeon's glove, gown, or in the operating room. The good news, in fact there's two bits of good news. First, that there is a pretty significant normalization of the toddler's gut microbiome with time as he or she is exposed to the world, the similar world as the other child. But the other A bit of research I think is really very exciting being done mostly at NYU is the idea of prior to doing a c-section, taking a vaginal swab, keeping that swab in a warm, moist environment, deliver the child by c-section, and then implant that bacterial component into the child's mouth, nose, and face. Ears, eyes, kind of all over the place, right? Yeah, basically wipe the face of that child. That research is early, but it's being done. And I think that we will see that the results will probably be related to an intermediate benefit, somewhere between vaginal birth and C-section, but in a better place than C-section. Because you hear about, I mean, you hear about the rise in autism, ADHD, like you mentioned, autoimmune diseases. Skin irritations, nut allergies, all these different things that, I don't know if those were around when you were growing up. Was that a common thing in children? No, they were around in autoimmune conditions, again, type 1 diabetes, celiac disease, lupus, all the various autoimmune conditions were around, but we're seeing that they're skyrocketing. And why? It gets back to one single term that we've talked about today called immunometabolism. The relationship between the balanced response of the immune system and our metabolic health, the control of our blood sugar, our blood pressure, whether we're obese or not, those things are skyrocketing and threatening the balance of the immune system. Beyond that though, The array and diversity and functionality of the gut bacteria is changing quite rapidly over time, primarily based upon the change in the human diet. That has a direct role to play in the balance of the response of the immune system. It should be not too high, not too low, the Goldilocks zone. Not enough immune function, we develop risk for infection. Too much immune function, we react to things, even react against ourselves, hence explaining... In providing the answer to your question, why are we seeing such a rise in allergies to nuts and other things and autoimmune conditions as well? Let me tell you something before I forget. Yes. Is this what you're going to tell me before I ask you? My wife and I are in a lodge just in the northern part of Patagonia in Chile. And I'm watching TV. It's in Spanish, of course. And there's my interview, your interview with me. Really? On Chilean television in really good Spanish that was lining up with our mouths. It was perfect. That's great. Yeah, yeah. We dub our content. We have, you know, the whole AI dubbing the whole thing. So we have over a million subscribers in Spanish on our Spanish channel. And somewhere around five or seven million views, I think. a month in our Spanish content. We have Portuguese channel as well. Wow. So our mission is to serve humanity in the biggest way possible with this information. And so I go to Mexico a lot. My fiance is from Mexico and we go there a lot for her work. And I'll be walking down the street and people come up to me and playing the Spanish content. Right. Si, en tu casa como esta. Yes, exactly. And they're like watching the content in Spanish. Yeah, yeah. And they're so grateful because they don't have access to you if they can't understand English. with your English content unless your book's translated in Spanish. But the video content is really helpful for them to listen and watch at the same time. Not just subtitles in Spanish, but actually hearing it. And I think more people are starting to get into that and dubbing their content. It's a big investment, but it's been worth it for us for the impact. Yeah. Well, I will explore that with you further off camera because I think I would love to do that with my podcast. Because again, you know, the mission is to get the information out. So yeah, it's a... I mean, it's investments, so it's like it took a couple of years for us to kind of break even, I guess, on the ad return on YouTube or whatever. But for me, it's more about changing lives, helping people, service. Understood. And it's worth the investment in my mind to help more people. But that's cool that you got to see your content. It was on TV, huh? It was on TV. Now, it may have been on YouTube, but I think it might have been on network. Maybe they took a clip. Well, we also were on PBS as well, so in America. So it's probably not in Chile, but that's awesome. Something that's been a hot topic lately in culture and society around sugar and glucose spikes. How related is the amount of sugar we eat, the amount of glucose spikes we have in a day, to dementia or Alzheimer's? And is there a way to understand our glucose spikes better or to cut out sugar in a way to support us in this process? Well, I think the relationship of our consumption of sugar, and I'll need to kind of define what that means, what is sugar, is profoundly related to Alzheimer's risk and Alzheimer's progression. You know, one study demonstrated that there's a profound relationship between the number of sugary beverages each day and Alzheimer's risk and actual shrinkage of the brain, even more profound. And sugary beverages, we're thinking of... soda, etc., includes fruit juice. So let's be clear. Orange juice, lemonade, apple juice, cranberry juice. That the sugar content of these juices is equal to drinking a Coke or Pepsi. Perhaps Mountain Dew's really got a lot of sugar, but we're talking 36 grams of sugar in a 12-ounce or 16-ounce can or glass. So having said that, it's a clear and present danger. Mechanistically, we've already covered why it happens because we're threatening mitochondria, we're threatening to change those wonderful supportive immune cells to becoming the evil twin and destroying brain cells. And it all comes together. We are now connecting these dots. My colleague, Dr. Robert Lustig, has really gone a long way to really defining the biochemistry in terms of how this is happening. And what are then these relationships between these dietary trends and brain health decline? But yet, we're seeing ever increasing amounts of other information kind of leading us to believe that, well, you know, there are bad sugars and good sugars. And, you know, the reality is that the most threatening sugar of all is not glucose. What is it? It is fructose, by far and away. What's the difference between glucose and fructose? So they are totally different molecules in terms of the number of carbon atoms. And importantly, in table sugar, it's both. It's 50% fructose and 50% glucose. They are bonded together. We consume that table sugar and then we, in the intestine with an enzyme called sucrase, we break it up into fructose and glucose. Fructose doesn't require insulin for its metabolism and, as we may have talked about before, immediately is metabolized into something called uric acid, which is a profound threat to our metabolism. Glucose is absorbed and is used as fuel. Fructose is a powerful mitochondrial toxin. Toxin. Mitochondrial toxin. Fructose. Fruit sugar. Fructose. Now, having said that table sugar is 50% fructose, recognize that there exists something out there called high fructose corn syrup, which has an even higher percentage of fructose that is cheap and really, really sweet, which is why it's the go-to sweetener for... You know, about 60 to 70 percent of grocery store shelf packaged products contain at least some added sweetener. By and large, it's high fructose corn syrup or a derivative thereof. Fructose is a powerful threat to our immune function, a powerful threat to mitochondrial health. That's why it threatens our immune function and clearly a clear and present danger as it relates to brain health and Alzheimer's risk. So let me take us back, let me wind the clock back a little bit to when we started today. You presented some very sobering statistics about not just where we are in Alzheimer's, but where we're going. I think you talked about 2050 with tripling of the prevalence of Alzheimer's at that time, far outstripping the aging of our population. And I think the query was, why is it happening? And my response to you was, because of the changes in our metabolic health. The number one threat to our metabolic health, and I believe I said it before, is our fructose consumption. So how much fructose consumption can we have where it doesn't threat our metabolic health and brain health? Wonderful question. And indeed, humans consume fruit sugar. It goes by the name of fructose. That's where the name comes from. And we can handle at any given time about five grams of fructose. That's an apple. One apple a day. No, at a time. You can have a couple of apples in a day, but you don't want to load your body, you don't want to load your digestive system quickly with any more than about five grams of fructose. One apple is about five grams of fructose. That's right. And what is that, like a banana is five grams as well or a similar range? So the issue isn't necessarily the amount of fructose that a particular fruit contains. Bananas are about midway, melons are higher, watermelon, honeydew melon, cantaloupe are higher. There's a scale in terms of fructose consumption. One doesn't eat as many by mass, wouldn't eat as many blueberries perhaps as a big apple, but having said that, our small intestine can handle about five grams of fructose at a time. Time is an important operative word. Why? Because it's like chugging a glass of. Orange juice or Dr. Pibb or whatever it may be, you're bombarding your digestive system with a huge fructose load, far more than it can handle. Like a rush of it. That's right, a rush. And it's far more than your small intestine can process, which is about five grams at any given moment. You don't eat all the fructose or consume all the fructose in an apple. You don't chug an apple. Right. It takes time. You got to chew it. You got to, you know. But you do drink a glass of orange juice or apple juice quickly. Not only that, but an apple contains fiber that slows the release, the absorption of fructose. It also contains vitamin C, which is relevant because the downstream consequence of ingesting higher amounts of fructose is the creation of uric acid, which affects your metabolic state in a negative way. But vitamin C helps to offset that by augmenting. Your ability to excrete uric acid. So eat the apple or two a day, keep the doctor away, but don't drink the apple juice. Or if you do, water it down. Interesting. So have less concentrated, a little bit of water. And you won't notice a difference. Yeah, exactly. So what about people that just love to have a fruit diet? They eat tons of fruit, a big bowl of fruit. They believe it's very healthy for them. It's got fiber, it's got nutrients, it's got vitamin C, and it's a big bowl of fruit. Is something wrong with that? Well, it's not ideal. Is it better than processed? Fruit or sugars, though? Is it better? I would say yes for the reasons that you delineated. The fiber, the vitamin C, the other nutrients, the bioflavonoids, the polyphenols, you name it. But if you're going to do that, then pace yourself, eat it slowly. This morning, with my breakfast, I asked for a bowl of fruit. And the hotel brought, it was massive, this bowl of fruit. And at the end, the waiter asked me, well, do you want to box this up? Because you left. Two-thirds of it, I said, no, I didn't really want to do that. So what did I have for breakfast this morning? I had three eggs over easy, a garden salad for breakfast, who knew, with a side order of olive oil. A lot of fiber. A lot of fiber, a lot of good fat, and what turned out to be a very small bowl of fruit because I didn't eat it. And two cups of black coffee with allulose sugar in it. which acts as a GLP-1 agonist. So the allulose sugar, which you're on the board of a brand called RX Sugar, is that right? That is correct. That creates this allulose sugar, which is a GLP-1 agonist. What does that mean? It means it stimulates the GLP-1 receptor in a positive way as the natural GLP-1. Producing the body from the L cells in the small intestine would do Action a similar way as the GLP-1 ozempic like drugs They're all considered GLP-1 agonists. What is GLP-1? So this is a hormone that regulates things like appetite regulates the emptying of the stomach Back centrally in the brain To regulate how much food we consume and even has a role in terms of how insulin does its job in the body as well. We all produce this. We all produce this to varying degrees. But some of us produce less of it over time if we're eating too much sugar or processed foods. Is that part of it? That may happen, but I think that eating sugar actually immediately stimulates the body to produce GLP-1 as does fat and fiber. Interesting. So GLP-1 is something that helps us To process food better or to have less? What does it help us do specifically? So this glucagon-like peptide is, you know, when we're eating, there's a lot of signaling going on in the body that, you know, suddenly there's a big change about to occur. We're going to load the body up with who knows what and how are we going to deal with it and how much should we be consuming and why don't we just keep eating? So... This is a way of regulating appetite that's built into our physiology that now starts to to metricize what we're eating in terms of quantity and quality in terms of calories derived from fat versus carbohydrate so that we're going to eat an appropriate amount of food. Other hormones are involved like ghrelin and leptin as well. With time we can become less sensitive to these chemicals. We certainly become less sensitive to leptin which It also regulates our appetite such that we become, like we can become insulin resistant, we can become leptin resistant as we constantly bombard our bodies with foods that challenge the production of leptin, we become resistant. So we become less sensitive to the signaling of leptin and therefore we might eat too much. I mean, there was an attempt in the past to give people leptin as a way of curbing their appetites, didn't seem to work. But. Clearly the GLP-1 agonists are working. I mean, people aren't just taking these drugs because the celebrities are talking about them. They're working extremely effectively in terms of weight loss and in control of blood sugar as well. In the New York Times this morning was a fascinating article talking about addiction and the effectiveness of GLP-1 agonist drugs in terms of Addiction, even things like alcohol consumption. So are these drugs helping you essentially... Not eat more or they help you digest the foods you're eating faster? Actually, they slow gastric emptying so that that food will be around longer and will then be available for digestion perhaps longer. But I think the former is probably much more a reason that we just, our appetites are curbed and we're eating less food. So you feel fuller because the food is inside of you longer. Yeah. And the stomach because it's not emptying becomes more distended and that is an electrical event we sense that the stomach is becoming distended and as such it sends a signal to the brain that we should stop eating it's you know in the in days gone by a procedure was done called a gastric sleeve where the outflow of the stomach was compressed with a device uh to and as such the stomach would then distend more and that would send signals to the brain doing the same type of thing wow What about people that do, I guess, shrink their stomach? They do a surgery to, I guess, shrink? I don't know what that's called. Yeah. What is that called? When they open the stomach, they cut it in half, shrink it or something? Well, what's been done is called gastric bypass operation, whereby the outflow of the stomach is diverted such that, again, and the stomach is made smaller as well, really with the same goal in mind. And interesting. There are some pretty profound metabolic changes that happen from that, like better insulin functionality. Really? Yeah, I mean, you don't, in my position… You don't want to go there. I don't want to, you know, it's kind of hard to admit because, you know, I think it's an aggressive procedure, but that's what the data shows. And similarly, you know, again, I didn't want to spend an inordinate amount of time talking about these drugs, but I think people are really interested. I think it needs to be talked about. That's interesting. Because I think we should look at upsides and downsides of everything that's available. I guess the one thing that you mentioned that was a red flag for me, I guess, is like if the food is not digesting and it's sitting there and it's like, I guess, just kind of blocked up, does that mean you have more constipation? Or is it just, okay, your stomach is bigger for a period of time because the food's still in there? Shouldn't the flow want to have like a natural flow as opposed to a blockage like a dam? I think that is correct. I think, you know, the more physiologic we can be in terms of interventions and recommendations, the better. You know, one of the feared complications of these GLP-1 agonist drugs is something called gastroparesis or paresis, which means basically a total paralysis of the stomach. And that can be life-threatening. So it's not common. It is described as one of the concerns of using these types of medications. And as we talked about earlier, in the interventional trial for Parkinson's patients, gastrointestinal issues were very, very common. Interesting. So what would be the three to five natural interventions or environmental or food interventions that we can take today? To prevent us from getting Alzheimer's or help us optimize the longevity of our health and our brain health for the future without medical interventions. Let me first characterize the use of a continuous glucose monitor. Let's maybe not call it a medical intervention. Okay. But it's an assessment tool. Yeah. I am very grateful it's now not. Is it now available non-prescription, i.e., it's a way that people can really gain a fundamentally important metric about their physiology. And the reason I, you know, again, it's like a bathroom scale to me, which anyone can have and should have. You're learning about your body weight, you should learn about your blood sugar. So what then is this ideal diet that Dr. Perlmutter is now going to describe? To your audience, and I think that we should consider the question as more along the lines of what's the ideal diet for you? For you. Personalized. Right? And I don't know how to answer that question. I do know the broad strokes, and we can talk about the broad strokes, but I think ultimately, to me, an ideal diet is one that keeps your blood sugar under tight control. And how high do you want your blood sugar to be if you're using a glucose monitor? What's like the... parameter for you? Well, If your blood sugar spikes to 160 after a carbohydrate meal, you might think that's a high number, 160, 180, but it's not really that important because it's going to. And I think that what we look at in looking at these measurements, it's not the spike, but how quickly it returns to baseline, how long it stays elevated, and again gets back to, if it comes back to baseline very quickly, then the area under that curve is pretty reduced. If it's. Spikes and stays elevated for a longer period of time, then we have a larger area under the curve that translates to poor control of blood sugar, threatens insulin sensitivity that becomes a powerful threat to brain health. So you think having a glucose monitor, at least for a couple of weeks of time, is something that people should consider so that they just have more information about their own health? That's right. But you were pretty healthy before you used a glucose monitor yourself, right? Well, when I started using the glucose monitor, I was very pleased with my results. But, you know, I can't be one of those do-as-I-say-not-as-I-do individual. A, B, my dad died of Alzheimer's and it was awful. Yeah. And I don't want that to happen to me, but more importantly, I don't want my family to go through that again. So, I think it's important for me to stand as an individual who practices what he preaches. Yeah. And so, therefore, when I started using a CGM, the continuous glucose monitor, I was happy with the results. But I think, you know, this isn't something you have to do day in and day out for the rest of your life. You begin to develop a sense as to what your blood sugar does when you do or don't exercise, when you do or don't get a good night's sleep. And fundamentally, how do your food choices relate? And how do your supplements relate, as a matter of fact? Interesting. As well. And how do other things, you mentioned, we talked about allulose, relate to blood sugar? And I think people... Using a CGM are going to be surprised by what they learn about themselves. The broad strokes, avoiding ultra-processed foods would be on the top of the list. Number two on that list would be avoid ultra-processed foods. Probably going to be three through five. Really? Yeah, beyond that is... Ultra-processed foods. It's such an issue. Packaged foods, processed carbs, processed grains are ubiquitous. And I don't care if, you know... They're organic, they were made by this or that, you know, company that has a great vegan, non-GMO, everything. Yeah, great startup. I want to be supportive of these people. It's the processing of these foods that leads to the fact that they're pre-digested, basically. And when they are consumed, your blood sugar goes up. So what about like protein bars and things like that as well? It's not a natural food. And I think that... for me, I've done my best to avoid those types of packaged foods. I mean, is there a time if you're at a conference, sitting in a conference all day? Yeah, not really. You know, the truth of the matter is... Just fast a little bit, yeah. And your brain's going to work pretty well. Have a good breakfast, go to the conference. Maybe there's a good luncheon or not. So I don't really see a time and a place. If you're going to be on the trail, hiking, and you need to have something in your backpack, Oh, you could put an apple in your backpack in a bag of mixed nuts just as easily as you can put a protein bar. Could there be a protein bar that is acceptable? There are, and there are a few of them out there that are not too bad. You've got to watch the sugar component. You've really got to watch what kinds of fats go into it. Because, again, processed fats that are threatening and good fats that are not just... Dr. Good for you, but fundamental for your health. What about dried meats or kind of a jerky with no sugar or something? It's just salt and meat, dried or smoked, something like that. Dr. Well, dried versus smoked I think is really important. I think the process of smoking may introduce chemicals that are not necessarily going to be good for you. Interesting. Dr. Dried, basically dehydrated, I don't think is a significant risk. They do contain that does contain a lot of purines ounce for ounce purines are metabolized into uric acid Which is something else we can monitor and we can monitor our own uric acid with Going on online and buying a uric acid monitor that requires a finger stick unlike the continuous glucose monitor But we'll see what the future holds. Is there any processed foods that you think could? Benefit in any way that are out there that are like okay these are minimally processed these are in a package or in a bag where they're not that harmful? Yeah there are in fact you know there's a couple that really stand out there is one minimally processed type of buckwheat called Himalayan tartary buckwheat HTB. Yeah who's the person who works on that? Dr. Jeffrey Bland. I remember. Yes, Dr. Jeffrey Bland. Oddly enough Dr. Austin Perlmutter, who knew? So they have just published a report looking at changes in what are called methylation patterns, looking at the changes in the markers on human trial, human DNA over time in people who are consuming this HTB, Himalayan tartary buckwheat, and really some phenomenal results. Interesting. Now you mentioned briefly that you're... Your father passed away with Alzheimer's. Was that one of the main reasons you wanted to get into the medical field and study this? No, my father was one of the main reasons that I got, you know, without question. I mean, I mean, you know, it was, I think pretty much in the book that I was going to be a physician and for a number of reasons. I mean, my first choice was meteorologist, specifically a hurricane specialist when I was young. When I was in fifth grade, I used to ride my bike to the National Hurricane Center in Coral Gables, and they had all these displays about how does a hurricane form. And they used to chart hurricanes. They used to give lat and lon, the latitude and longitude of the hurricane, so that you at home could chart the progress of this hurricane on your home hurricane map. They don't use that anymore. But anyway, I decided I wouldn't do that because as I got older, I realized Oh, you had to study chemistry and math, which turned out to be, you know, my favorite subject, but anyway, so to become a doctor. But I think the main thing that, two main things that spurred me on were his compassion towards his patients and my curiosity with just medicine and how the human body works. Was he studying Alzheimer's as well? No, he was a brain, he was a neurosurgeon, so, but. It was always about the brain. I mean when I was 11 years old at the dinner table he would say, well David what is Marcia Fava Bignami syndrome? Marcia Fava Bignami syndrome and I'd say well I don't know. He said that's what Italian men get who drink too much red wine and I would never forget. And when you're young you can remember stuff like that. Wow. Yeah it was and then as I became like in my early teens 13, 14 I used to be able to go in those days, you know, less of a risk, I'd go into the operating room. I would scrub in. Wow, with your dad? With my dad, yeah. Wow, what was that like? He was doing like brain surgeries? Doing brain surgery. When I was 14 years old, I was in the operating room holding retractors while my dad was taking up brain tumors. Come on, really? Yeah. How many brain surgeries did your dad do? Oh my gosh. You know, several a week. But he did a lot of back work, too. Hundreds or thousands. Thousands, yeah. He was a wonderful surgeon. And when you couple that ability with compassion, you know, because it was not always good news after the fact. Sure. And I watched him do that. I watched him interface with families. And I remember, in particular, one night, he woke me up. He said, I've got to go out to the emergency room at South Miami Hospital. I went out, it was one o'clock in the morning, and a man had dove off a wall drunk in the Keys, Florida Keys, broken his neck. Brought him up to South Miami Hospital. And my dad had to put tongs, like ice tongs, in his skull. Ice tongs connected to a rope, connected to a pulley, connected to a weight, to pull the neck up. to keep him from moving his neck further prior to him being able to go in and then stabilize the fracture. Wow. So I watched him do that in the emergency room and then the man's mother and father showed up. And I'll never forget the interaction that he had with that mother and father. I was, you know, in my early teens. And he explained that he had broken his neck. And I remember the mother literally almost fell over to the extent that my dad had to help her into a chair. And she grabbed her heart. But the way he dealt with that situation was a horrible situation for the parents to find out. And then son was still drunk, so he was kind of still out of it. I won't forget that. And I won't forget one other moment of compassion. We were fishing and he caught a small fish that we weren't fishing for. And he unhooked it and threw it back in the water and the fish was not doing well and he watched that fish for probably 20 minutes and kept talking to it and saying, you can do it, you know, go back down. Wow. Because sometimes when you catch a fish, it doesn't do well. I stopped fishing and watched him and heard him and finally the fish fluttered and went down and just that level of compassion really just had an imprint on me at a time in life when you are imprintable. And I think it was a Dan Fogelberg song that I quoted at his eulogy. I want to go off just for a second. Go ahead. I'm sorry. Go ahead. So the Dan Vogelberg song in it, it's called The Leader of the Band, and he says, my life has been a poor attempt to imitate the man. I'm just a living legacy to the leader of the band. And I let that one hang on the audience. Because, you know, I've kind of lived my life trying to live up to that. Really? Yeah, I really have. Wow. You know, he wasn't perfect, nobody was, but like your father, as you describe in your book, set the bar pretty high. Luckily for us, they did. And that wasn't their mission, but they did by example. What was the biggest lesson he taught you beyond compassion? The notion of noblesse oblige that John Kennedy talked about. It basically means that if you're gifted and we all are, whatever that gift is, you're obligated to use that gift in a way that serves humanity. You know, I get the message that I'm pretty clever about certain things. I know that at this stage of life. I'm going to be 70, so I can say that I've understood that over the years that I have a pretty good brain, and it has allowed me to do the things that I've done, to accomplish the things I have accomplished. But to accomplish things for accomplishment's sake is one thing, but to accomplish things that fulfill your obligation to others. We are obligated. I think it's a task that he charged me with by letting me know about that notion. And that stands right up there with... That is part of compassion. To be compassionate to others is to use your skill set to benefit them like you do with this podcast. I mean, it's all about giving back. And we talked about, you know, why do you have your podcast translated in Spanish? Because they need... The wonderful information that you're giving them. It's not a moneymaker, face it, but that's our obligation. Absolutely. How long, you say your dad died of Alzheimer's, is that right? Alzheimer's killed him, and I think it's really important that people understand that Alzheimer's itself is the number three cause of death in America. It kills people. Now, to be clear, Alzheimer's patients generally have... You know, quite a few other diseases going on because they're metabolically compromised. Heart disease, diabetes, etc. And becoming a type 2 diabetic is associated with about a four-fold increased risk of Alzheimer's. So these things ride together, but clearly the Alzheimer's took his life. How long did he have the Alzheimer's for before his death? Well, how long had he had the clinical manifestations? Probably about seven years. But vis-a-vis our earlier discussions, it likely started 20, 25 years earlier than that. But you started to see the symptoms for the last seven years, is it? Most of it. Well, I diagnosed it. Wow. And I remember the moment I diagnosed it. And at that moment, I said to myself, how could I have ignored this as a neurologist? And of course I would ignore it. It's my father for crying out loud. But it's my work. I did it every day. I made that diagnosis countless times every single day in my medical practice. You don't want to see that with your father so maybe you're not… I didn't want to see it. I couldn't see it. I kept myself from seeing it. But finally in one statement that he made I was about to argue with him that he was wrong that dad… No, as a matter of fact, it was a different way when I finally got it and I said, wow, this is where we are. Put your seatbelt on because you know what's going to happen. I know better than anyone what's going to happen. This has been my work for decades. I knew very well. And then I had to tell my other family members, five kids. I had to tell my four siblings what's going on here, what to expect. Are you the oldest? I'm the youngest. Wow. You'd think I was the oldest. I get that all the time. Either the oldest or the youngest. It's either one. What were the biggest lessons you learned in that seven years with your father? Compassion and get to work. Get to work. So, yeah, I've devoted myself to this notion. And we're living in a world that, again, wants us to believe that our lifestyle choices don't matter. everything. They're everything. This disease is not caused primarily by an accumulation of beta amyloid. It's the targeting of beta amyloid that is the focus of all these wonderful new drugs that are being FDA approved. They aren't working. It's a metabolic issue. That's what I yell from the mountaintop. And we've got to rein in our metabolism to help keep the brain healthy and resistant to the problem in the first place. and also as a therapeutic intervention. It sounds like a glucose monitor can be the first step to understanding your own personal data of how your foods, your environments, your workouts, your supplements are impacting you in a positive or negative way so that you have better data to make better decisions. Yeah, and I think it really stems from our beliefs. There's a long, difficult... quote from Mahatma Gandhi that says, our beliefs become our thoughts. Our thoughts become our words. Our words become our actions. Our actions become our habits. Our actions, our habits ultimately become our destiny. And i.e. our beliefs become our destiny. Our beliefs, if we believe that we can live our lives and That medicine is going to save us will be our destiny. That we will be destined to these diseases that we so fear. People fear Alzheimer's more than any other situation at the end of their lives. Really? The ability or the lack of their ability for self-care and becoming a burden to others. And relying on other people for everything, yeah. You know, Robert Kennedy said some... men see things as they are and say, why? Others see things as it could be and say, why not? I think these days it should be some people. Let's make it politically correct. The point is, how it could be is no Alzheimer's. It could be eradicated. We could cut it in half. We could absolutely cut it in half if this messaging could be worked into policy. We used to have a much fitter country and world though, didn't we? Yeah. Fitter. Like we used to move more and not eat as much processed foods. Well, we've gotten really away from our Paleolithic ancestry, which is basically genetically who we are. We're still Paleolithic individuals and we are still, you know, our whole physiology via our genetics is designed to express itself in a way that keeps us healthy, provided it receives the external environmental signaling, i.e. food, etc., that is in alignment with our genetics, and it is not. But also, I say that with the caveat that the lifespan 100 years ago was a lot shorter than it is now. Isn't that correct? Even though we have more diseases and obesity and struggles now, we still have a longer lifespan than 100 years ago. when we were eating less and less processed foods, I guess. Well, what is lifespan? And when you talk about the lifespan of our population, if you were to determine the lifespan of the population, look at In 1900, you take a thousand people and ask yourself, how long did they live? And then you make the average. Well, in those days, there was a lot of childhood death. There was a lot of infant mortality. There was a lot of deaths around childbirth. And that shortened lifespan. There was a lot of deaths from trauma, a lot of deaths from infection. And those things, paying attention to those things, improved our lifespan. And you're right. Lifespan did increase over time, but interestingly now in the past four years for the first time in human history lifespan is declining. Really? So it's finally caught up with us. Really? We've really kind of... What is the lifespan for men and women in America currently? So we're in the mid 70s now for men and late 70s for women. And we can do so much better than that. Is that, I mean... And what's killing people now? It's not... It's not as much the infectious diseases, what's killing people, I mentioned it earlier, according to the World Health Organization, number one cause are chronic degenerative conditions that rob us of our ability not just to live a long life, but to have a longer health span so we live a healthier life. And these are conditions caused by disruption of our metabolism. We've closed the circle. And these are influenced by our lifestyle choices, moment to moment. When you hear that the lifespan is 77 or whatever in men, how does that affect you mentally or emotionally as you get closer to 70? You know, it's not something I like talking about, but how do you approach life with that information? Not saying that, oh, my life is over in a certain amount of years, but how do you think about it then? And I'm assuming that you have a lot of friends and colleagues and people in your life that you've lost as well as they've gotten older and you've seen people die. Yeah. How does that impact you at this season? Well, I have to admit, I certainly don't dwell on the fact that I'm where I am, you know, on the chronological clock. I do know that my biological clock is... puts me in the low 60s that's certainly that's great that's great yeah yeah you look very healthy if you just said 70 i didn't think you were 70 so i'm not there yet i got a couple months to go but um you know i'm not middle-aged i mean if we're gonna die at 75 so 37 and a half is the peak right so that's middle i'm well beyond middle age i have to admit i don't think about it uh i uh but you know uh james uh james taylor wrote a song uh called The Secret of Life. And The Secret of Life is enjoying the passage of time. Any fool can do it, there ain't nothing to it. Einstein said he could never understand it all. The planets are spinning through space, the smile upon your face. So I think it's just really enjoying, recognizing that time is passing and enjoying the various phases of the moment. It's a good way to live. I, you know... I play a lot of pickleball and the people I play pickleball with or that are playing pickleball where I play pickleball I'm about the middle of the age of those individuals so they're people wow a lot older than I am playing pickleball so that's encouraging. I hear paddle sports are some of the best ways to improve your brain function and your extend your lifespan too. That's right and I especially and I'm really excited that outside our your studio you There's a table tennis, which is great because things happen so quickly. You've got to think very, very quickly. And pickleball is the same thing. But you're moving a lot. So you play a lot more doubles then, huh? It's all doubles that we play. And I think that's becoming much more popular. But you have to be a little bit more careful at this stage of the game. You don't want to hurt yourself. A, you don't want to have the injury. And B, if you're injured, then you can't exercise. You don't want to stop exercising. Exactly. Exercising is, I think, the most important tonic for the brain. In multiple studies, if you want to enhance the growth of new brain cells and nurture those good-sided microglial cells that are there to help you and love you, that's what exercise does. So rein in your diet and make sure that you exercise every single day. This is powerful, David. I appreciate you coming here. So much information in this. I want to send people to your site. Dr. Perlmutter.com. You're all over social media, David Perlmutter or David Perlmutter MD in certain places. We'll have all this linked up as well. You've got 15 books. You've got more on the way. How can we be of service to you today? What can we do to support you? Gee, that's a good question. I'd say... Yeah, look at the information I'm putting out, think about it, and, you know, recognize that there are two sides to every story. And be open-minded that some of the things you may be hearing reference your health may not necessarily have your interest at heart. How does it serve me? It makes me happy to think that, you know... There are some people who are going to hear my message and will be better off for that. And that's the goal. I appreciate that very much. That's great. Is there a recent book we should send people to, to check out? My last book was called Drop Acid. That has to do with uric acid. My next book is tentatively called Brain Wars. And Brain Wars deals with the war in your brain between the good and the bad microglial cells. and how we can absolutely affect the outcome of this confrontation. Brain Wars. I like it. I asked you this question last time, three truths. I'm curious if you have different truths this time. If you could only leave three lessons behind to the world at the end of your life. You get to continue to create what you want, achieve, live the life you want, but for whatever reason you got to take all of your content with you or it's erased from our existence. But you get to leave behind three lessons. Three things you know to be true. What would you leave behind? What three truths? Well, I don't know what I answered last time, but what resonates with me right now is be as compassionate as you can to everyone in your life, everyone you interact with. We need that more than ever. Number two is be a good listener. And number three is express your gratitude. I'm grateful for you, David. I appreciate your consistent research and wisdom in bringing this information to people. And I appreciate you letting me ask you questions that are like, can you explain this like I'm nine so that I can understand this? Because I think we hear these big words and terminology and I don't fully understand them. And I'm interviewing experts like you all the time, but I still like want to simplify these things. So I appreciate you simplifying the complex for me and our audience. Appreciate you being committed to finding solutions, whether it be through organic interventions or medical interventions and being open to all possibilities on how you can help people with Alzheimer's or other things to support their brain health and their body health. And I'm just grateful that you're still on a mission to improving your health. And I hope that we see you around for a long time because I know your wisdom, we need more of it. So I'm grateful for your research. Well, thank you for that. Your commitment. Your dedication to serving humanity at the highest level. Well, and I want to say to you that I think we have a very special connection. And the reason I say that is because I don't know how many years ago it was that I sat in this chair and we spoke, but I feel like I never left. I feel like we're just continuing on where we left off. And that's very, very special. And I'm grateful for that. I appreciate it. Yeah, we'll do it again. We'll do it again. I'm excited. When your next book's out, we'll have you back on. Final question for you, David. What is your current definition of greatness? Greatness is using the gifts that you have for the betterment of our planet. And I believe that's pretty similar to what I said last time. I don't know. We'll check. We'll check. Make sure. We'll see. Exactly. What did you say last time? I'll look and see what it said. David, thanks so much for being here. Appreciate it. What we had found was that when people get a question that they're curious about the answer for, the question in and of itself is sufficient to trigger a spike in activity in the dopamine processing areas of our brain. And dopamine is thought to be this reward chemical, but it's actually more about chasing rewards emotionally.