FoundMyFitness - #086 How Micronutrients & Exercise Ameliorate Aging | Dr. Rhonda Patrick

Episode Date: March 6, 2024

Download the 9-Page "Cognitive Enhancement Blueprint" Discover my premium podcast, The Aliquot Join over 300,000 people and sign up for my newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more In today's episode, I'm bringing you along to the American Academy of Anti-Aging Medicine's Longevityfest Conference, where I had the honor of presenting a keynote last December. We'll explore some foundational yet effective tactics to enhance longevity and prevent diseases. Additionally, we'll delve into more intensive lifestyle modifications that, despite their demands, offer significant longevity benefits.   In this episode, I discuss: (00:00) Introduction (04:48) The importance of vitamin D (09:08) How vitamin D deficiency affects all-cause mortality risk (12:34) Optimal vitamin D levels & supplementation (14:20) Why magnesium deficiency impairs DNA damage repair (18:00) Dangers of inadequate omega-3 intake (20:17) The correct omega-3 index level (24:42) How to correct vitamin D, omega-3, & magnesium inadequacies (26:27) Vigorous exercise is the best longevity drug (28:00) How increasing VO2 max affects life expectancy (32:46) Protocols for increasing VO2 max (35:37) How to measure VO2 max (36:44) What it takes to reverse 20 years of heart aging (39:41) Blood pressure benefits of vigorous exercise (40:58) The BDNF brain benefits of vigorous exercise (44:08) How vigorous intensity exercise improves focus & attention (45:21) Exercise protocols for maximizing BDNF (46:23) Anti-cancer effects of vigorous exercise (48:40) The benefits of exercise snacks ​ Watch this episode on YouTube Show notes are available by clicking here  

Greetings listeners. In today's episode, I'm bringing you along to the American Academy of Anti-Aging Medicine's Longevity Fest Conference, where I had the honor of presenting a keynote this last December. We'll explore some foundational yet effective tactics to enhance longevity and prevent diseases. Additionally, we'll delve into more intensive lifestyle modifications that, despite their demands, offer significant longevity benefits. If you would like to view the slides I presented along with this presentation, you can find this episode on my YouTube channel called Found My Fitness. In this episode, you will learn the evidence that vitamin D deficiency increases mortality

and my thoughts on achieving optimal levels partly through supplementation. Why magnesium deficiency reduces DNA damage repair and what this means for cancer and aging. You'll learn about the dangers of inadequate omega-3 intake and why you may want to measure your omega-3 index to make sure you were at least in the 8% range. You'll learn some practical takehomes for correcting vitamin D, omega-3, and magnesium inadequacies. Why vigorous exercise is the best longevity drug and how increasing VO2 max affects life expectancy. You'll learn some of the most evidence-based protocols for increasing VO2 max and how to get a good estimate of VO2 max without directly measuring it in a lab.

You'll also learn what science suggests it takes to reverse 20 years of age-associated structural changes to the heart. The brain and blood pressure benefits of vigorous exercise, and in particular, why vigorous exercise seems uniquely able to improve qualities of cognition, like focus, attention, and generally reduces the aging of the brain. You'll learn anti-cancer effects of vigorous exercise, and how exercise snacks can be used to break up sedentary time throughout the day, and why this is so beneficial. Before we jump off to the presentation and in the spirit of unwavering commitment to optimizing health and longevity, I've put together a guide that stands at the intersection of rigorous science and actionable strategies. It's a blueprint that draws on the robust evidence behind enhancing

cognitive function and delaying the aging process of the brain. You can access it now at BDNF protocols.com at no cost. Within this guide, you'll find a comprehensive exploration of the lifestyle modifications that hold the power to reshape your cognitive landscape. From the nuances of exercise to the specifics of nutrition and the strategic use of supplements, we delve into how these factors can significantly elevate your cognitive prowess and fortify your brain's defenses against times wear and terror. Central to these strategies is the pivotal role of brain-derived neurotrophic factor, B-D-N-F, a key player in maintaining and improving neural health. I also share a personal journey through Ronda's protocols,

which is a candid look at the practices I've integrated into my own life and the cutting-edge strategies I'm currently investigating. Each protocol is curated not just for its scientific grounding, but for its potential to make a meaningful difference in cognitive function and neuroprotection. If you are serious about optimizing your cognitive health and pushing the boundaries of what your brain can achieve, I invite you to download this guide at bdnf protocols.com. Once again, you can find that free guide at BDNF protocols.com. And now I invite you to listen to my presentation at the American Academy of Anti-Aging Medicine's Longevity Fest.

Good morning. Nice to be here today. I was just mentioning that my son eats about two cups of pomegranate a day, so his erolithin A levels must be off the charts. and maybe he'll live to be 100, but probably gene therapy is going to be involved in that. Today we're going to be talking about some of the, what I think are powerful lifestyle habits that can affect the way you age. So there's some what I call low-hanging fruit. So these are things that I think are really easy. It can be as simple as a, you know, dietary modification or a supplement you take. And then there's some things that are a little more effortful, which require effort.

And so that would, of course, be exercise. And so we're going to get into that as well. So the first part of the talk, we're going to just talk about optimizing micronutrient deficiencies. And in the second part, we're going to be talking about what kind of exercise and how it affects the way we age on a molecular level as well. So first up, I think there's really three main micronutrient deficiencies that I want to talk about for a couple of reasons. One, because they're widespread prevalence in terms of either deficiency or inadequacy. And two, because I think they played a very important role in a lot of physiological processes in our body that affect the way we age. So first, we're going to talk about vitamin D.

and most of you guys probably have already heard enough about vitamin D, but it's important to talk about because it's more than a vitamin, so vitamin D gets converted into a steroid hormone, and it goes into the nucleus of cells and interacts with DNA. So it recognizes a very specific sequence of DNA called a vitamin D response element. And this is encoded in our DNA. And that interaction, then, either turns genes on and activates them, or it does the opposite. It sort of turns them down and represses them. So it's very important for orchestrating. I mean, we're talking about over 5% of the protein encoding human genome is regulated by vitamin D, which is quite a lot. And so, you know, you can imagine if you're running a car and your pistons are firing out of sync with

each other. I mean, that's kind of what's happening when you don't have adequate levels of vitamin D. Your genes aren't being regulated in the way they're supposed to be. So things aren't being activated when they're supposed to be or repressed when they're supposed to be. So things are kind of, you know, going, going awry. And as they mentioned about, it's widespread prevalence in terms of inadequacy. So about 70% of the population has inadequate levels of vitamin D, which we'll talk about in a minute. It's about 30 nanograms per milliliter or less. And it's a very simple solution. And that's also why I like to talk about it, because it's almost just as simple as taking basically a supplement that costs a penny a pill. Vitamin D supplements are one of the most

affordable supplements out there. And there's really just no reason other than lack of, you know, education about vitamin D for people to be so deficient and insufficient. A lot of reasons for the widespread deficiency. You know, we make vitamin D3 in our skin. So UVB radiation is essential to make vitamin D3. Anything that blocks out UVB radiation is going to stop that production of vitamin D. So we're talking sunscreen. Melanin, which is the dark skin pigmentation that protects us from the burning rays of the sun, also is a natural sunscreen. So that is also a form of sunscreen. Also, depending on where you live, so in northern latitude, UVB radiation can't even reach the atmosphere, you know, several months out of the year. So when you combine some of these factors, let's say

you take someone with darker pigmentation from, let's say, East Asia, and they move somewhere like Chicago or they move to Sweden, where, you know, six months out of the year, you're not even getting that UVB radiation. You're talking about just a, you know, compounding effect on vitamin D deficiency because, you know, there've been studies out of the University of Chicago that have shown that, for example, African Americans have to stay in the sun anywhere between six to ten times longer than Caucasians with fair skin to make the same amount of vitamin D3 in their skin. So you're talking, I mean, it's a very, it's a compounding effect with respect to the melanin production as well. And then age plays a role. So as we age, you know, everything is,

less efficient. So, you know, a 70-year-old makes about, I think it's four times less vitamin D3 in their skin than their former 20-year-old self. So, and then, of course, modern-day societies that we have, we're inside, indoors, we're at our computers, we're in our cubicles, we're technology, you know, we're not out, it's not an agricultural society. We're not outside, you know, as, as much as we used to be. And so vitamin D is just not being made in our skins like it was, a years ago. So there's a lot of reasons why it's widespread. I like to show this slide. It was a study published several years ago. It was 2009. And it's showing when you knock out the vitamin D receptor in mice that it affects the way they age. So at the top of the panel, you can see that both

mice, that wild type and then the vitamin D receptor knockout, sort of aging the same. And then four months later, the vitamin D receptor mouse is just, it's an accelerated aging model. And, you know, yeah, it looks terrible, but like the organs on every level, things were sort of accelerated in the way they were aging. So it's just kind of a nice visual to see. But, of course, we're not mice. And I've always often wondered why mice even need vitamin D because, you know, they're nocturnal. And it's just one of those things where it's like, I don't know how much of that actually translates to humans. So let's talk about some humans. studies. We know that there's a lot of data out there, observational data that's correlated

vitamin D levels to low vitamin D levels to higher all-cause mortality risk, higher cancer mortality. But there's always that question of healthy user bias. Maybe people with higher vitamin D are outside and more physically active. And of course, you try to correct for as many, you know, confounding factors as possible, but you never really can establish causation. That's where Mendelian randomization comes into play. So this is, we, you know, we have a variety of genes that are responsible for converting vitamin D3 into 25 hydroxy vitamin D, which is the most, you know, active circulating form of vitamin D, and then subsequently into the steroid hormone, which is 125, a hydroxy vitamin D. Some of these genes that make enzymes, we all are different. And so some people

have ones that don't do it as efficiently. And so Mandelial, And then randomization takes these genes, these single nucleotide polymorphisms in these genes and says, okay, we're going to randomize them. People that have these genes that we know make them basically have lower levels of 25 hydroxy vitamin D and see what they're, you know, correlate that to health outcomes like all cause mortality. So it's kind of in a way of a way of randomizing people. And people that have genetically low vitamin D levels, independent of what their lifestyle is they have a much higher all-cause mortality, they have a higher cancer-related mortality, and they have a higher respiratory disease mortality with very little or no effect on cardiovascular

mortality. And there's also been, with randomized controlled trials, obviously you're not going to have a lifelong randomized controlled trial looking at mortality, but there's, you know, there's other biomarkers that can be looked at. One is epigenetic aging, which I'm sure you've guys heard about yesterday. So one study that took people that were vitamin D deficient, and it's important to start out with a cohort of participants that are deficient, right? Because if you already have someone that's sufficient, giving them a vitamin D supplement really shouldn't do much because they're already at a sufficient level. So these were African American individuals that were also overweight, and so they were very vitamin D deficient. They were given a vitamin D

supplement with 4,000 I use of vitamin D a day, and it decreased their epigenetic age by almost two years. So the question is, what is deficiency, insufficiency, adequacy? So technically it's kind of, I would say depending on what institute you're looking at, but the endocrinology institute defines deficiency as 25 hydroxy vitamin D levels less than 20 nanograms per mil, sufficient. C is about 30, getting, you know, so if you're insufficient, you're less than 30, but if you're sufficient, you're more than 30. And it seems as though the sweet spot for vitamin D is between 40 to 60 nanograms per milliliter. And, you know, there's all-cause mortality studies also looking at vitamin D levels. There's meta-analysis of these, you know, ranging from 1960s all the way to

the, you know, mid, like, 2015. And it's really, it seems like 40 to 60 is a really good. good sweet spot for the lowest all-cause mortality with vitamin D. As I mentioned 4,000, I mentioned 4,000 I used a vitamin D a day because that's the tolerable upper intake for vitamin D. So it's quite safe. And in general, 1,000 I use a vitamin D generally raises people's blood levels by about five nanograms per mil. So the key is to just get a vitamin D blood test. Do it, you know, after you're supplementing, make sure your levels are adequate because, again, a lot of these single nucleotide polymorphisms and genes that affect our enzymes that are metabolizing vitamin D also affect how we respond to supplemental vitamin D. And some people can require a much higher dose than other people. So really,

the key here is blood test and measuring. You don't know what you don't measure, right? So the next micronutrient I want to kind of shift gears and talk about is magnesium. And this, again, it's widespread inadequacy here. About half the U.S. population has inadequate levels of magnesium. So magnesium is found at the center of a chlorophyll molecule. So plants, you know, chlorophyll gives plants their green color. So dark leafy greens are a really good source of magnesium and essentially people aren't needing enough greens, which is why half the country doesn't have adequate levels of magnesium. Magnesium is a co-factor for over 300 different enzymes in the body, a lot of metabolic processes, so it's important for the production

of energy in the form of ATP, it's important for the utilization of energy in the form of ATP. But it's also important for repairing DNA damage. So DNA repair enzymes require magnesium to function. And this is where I think the aging, its role in aging comes into play because DNA damage is something that's happening every day. It's happening right now and all of us as, you know, our, we're metabolizing food, was we're breathing in oxygen, immune system slightly activated, whatever. It's constantly happening and our bodies are repairing that damage, but it's an insidious type of damage, right? It's not something that you can just wake up and look in the mirror and see, right? You're not, you're, you're, you're, scurvy is like, okay, my gums are bleeding and

things, something's wrong. You can see that, right? DNA damage isn't something that you really think about on a daily basis, but it's happening. And it accumulates with age. So you want to be able to repair that damage effectively, right? For many reasons. So DNA damage can lead eventually over the course of several decades to oncogenic mutations that could lead to cancer. And so there've been actually a variety of studies that have overlooked and correlated magnesium levels, magnesium intake, with cancer mortality. So there was one study that found for every 100 milligrams of magnesium intake, there was a 24% decrease in pancreatic cancer risk. And also another study that found that people that had the highest levels of magnesium,

they were in the top quintile, had a 40% lower all-cause mortality compared to people in the lowest. And then they had a 50% decrease in cancer mortality compared to people in the lowest. So magnesium is one of those. Again, I think it's best to try to get it from dietary sources, dark leafy greens are great source, but also supplemental forms of magnesium, I think, is a great sort of insurance, so to speak. So magnesium glycinate, magnesium nitrate, these are all pretty bioavailable forms of magnesium. The requirements for magnesium depend on age, gender, so men require a little bit more than women. It's somewhere like 400 milligrams a day for men and somewhere like 300 to 350

or something like that for women. If you're athletic, if you're sweating, if you're, you know, physically active a lot, use the sauna. You actually can require anywhere between 10 to 20 percent above the RDA because you do lose magnesium through sweat. So if half the U.S. population isn't meaning even that RDA, then you can imagine the physically active people are probably, you know, faring even worse because they're already, their requirements are even higher. So it's a simple solution, simple dietary modification supplement you can take to help sort of get your magnesium levels higher. So omega-3 is the is sort of the last micronutrient that I want to cover before getting into the next part of my talk. And omega-3, there's three forms of it. So there's ALA, which is found in

plant forms like black seed, walnuts. There's EPA and DHA, which are marine sources. So they're found in seafood. And there's a study out of Harvard that was published, gosh, it was like 2009. And this study identified the top six preventable causes of death. So these are things that are, you know, lifestyle related. So hypertension, for example, smoking, like not having, you know, avoiding hypertension, avoiding smoking. Those were, those were one of the, you know, some of the top six preventable causes of death. Well, omega-3, not getting enough omega-3 from seafood, So this was the marine source of omega-3, EPA and DHA, was in that top six. And researchers from Harvard had identified that not getting enough omega-3 from seafood was

responsible for about 84,000 deaths a year. And that was compared to trans fats. So trans fats were also consuming trans fats were one of the top avoidable, you know, preventable causes of death. Well, eating trans fats were responsible for 82,000. desk for you are pretty much the same as not getting enough omega-3 from seafood. And, you know, what's funny is that, you know, everybody knows about trans fats. You walk into any supermarket, any grocery store, everything's marketed. Oh, zero trans fats, zero trans fats. But nobody's thinking

about they're not getting enough omega-3. They're not eating enough seafood or fish or taking microalgae or, you know, fish oil supplement to get omega-3. And so I just kind of like to highlight that because it's again, I think that the way, thinking about food in that, you know, what are we, what do we need to feed our body, our metabolism? We need cofactors, magnesium, you know, vitamin D, omega-3. Like, these are things, if we focus on what we need to consume, we don't end up eating all the other stuff. And so, you know, people sort of get fixed at on what to avoid and don't think about what they're actually supposed to be taking in, what they're supposed to be eating. So the omega-3 index is one of the best measures of omega-3.

So this was pioneered by Dr. Bill Harris and his colleague von Schacky many years ago back in 2004. And it's measuring omega-3 levels in red blood cell membranes as opposed to plasma phospholipids. And the reason for that is because it is a long-term biomarker of omega-3. So your red blood cells take about 120 days to turnover. whereas your plasma phospholipids, it's more like if you get your omega-3 levels measured and it's plasma phospholipids, it's more like, what did I eat, you know, the past week or, you know, something like that. So it's kind of a comparison is, you know, fasting blood glucose would be the immediate, you know, biomarker and then the HBA-1C, right, is your long-term blood glucose level. So it's sort of

similar here. So omega-3 index is a really important way to measure omega-3 and it's now being increasingly used in many scientific studies. Of course, many, I think a lot of conflicting data out there also has to do with the fact that plasma phospholipids were measured. And again, it goes down to this, well, was it just that they didn't eat omega-3 in the last week or they did? And so we're saying they have high omega-3 because of that just recent dietary choice, right? So omega-3 index was, this is again from Bill Harris's group. He found, him and his colleagues found that people with a high omega-3 index, which is defined as 8%, at least 8%, had a 90% reduced risk of sudden cardiac death compared to people with a low omega-3 index of 4%. The standard, in the U.S., the omega-3 index,

most people, it's less than 5%, so it's about 4%. So most people in the United States are at a very low omega-3 index. They don't eat enough seafood and fish. So sudden cardiac death is reduced by 90% if you're in that high, high omega-3 index group, cardiovascular disease is the number one killer in the United States and actually in most all developed countries. Every 33 seconds, someone dies of a heart attack. So anything you can do to improve cardiovascular health is really, really on your side in terms of improving health span,

improving your lifespan. The high-o-o-metic mega-3 index, also from Bill Harris's group, found that people, again, with an 8% omega-3 index, had a five-year increased life expectancy compared to people with a 4% omega-3 index. So that was the low end. And it's interesting because in Japan, their life expectancy on average is about five years longer than in the United States. So our average life expectancy is five years less here than in Japan. And they happen to have an omega-3 index in general above 8%, whereas, again, I mentioned we're below 5%.

So sort of an interesting sort of observation that also correlates with the increased average life expectancy in a country that eats a lot of seafood. But this is what really, I think, is almost, it's eye-opening. It's part of the same study from Bill Harris's group where they stratified these participants and looked at their omega-3 index and then also look at their smoking. So the very, very top curve, the green curve, people live the longest if they had the 8% omega-3. index and they were non-smokers. And the very, very bottom curve, the red one was people that were smokers and had a low omega-3 index 4%. So they had the lowest life expectancy. But this is what blows my mind. If you look at the orange and blue curves, they're completely overlaid on top of each other. So people that had a high omega-3 index but smoked had the same life expectancy as people that didn't smoke,

a low omega-3 index. So essentially, if you just look at this data along, smoking was like having a low omega-3 index. And just, again, it's one of those things where, of course, it's observational data, you can never really establish causation. But I just feel like that's really eye-opening. Because again, everyone knows smoking is bad for you, but nobody's thinking about how we're not getting enough omega-3. And how easy is it to take a fish oil supplement, for example, or increase your, you know, salmon intake. So to summarize this part of my talk with respect to micronutrients, we talked about vitamin D, low-hanging fruit, as simple as a supplement, 4,000 I use a day is a pretty good start to get most people who are deficient to a sufficient level. That's been

shown in several studies. Getting people from a, you know, deficient level up to a sufficient level can be done with 4,000 I use of vitamin D a day. Omega-3 fatty acids. Omega-3 index, I'm getting the omega-3 index test, you want your levels to be in the 8%, you want to be high. And then there's been studies showing that it takes around 2 grams of supplemental omega-3 to get from a 4% omega-3 index to an 8%. It's really not that hard. And then, again, omega-3 is found in prescription form. I didn't go into all the randomized controlled trials today because that would take the remainder of my time here. But you can't. can get omega-3 in purified Atholester form, either in the form of EPA-only, Vesipa,

or DHA plus EPA-Lovesa. And those are prescribed in four grams a day per dose. And so what I said was, you know, sort of conservative, it takes about two grams a day just to get from a-perance, on average, 4% omega-3 indexed in 8%. And again, it's as simple as getting the test done and, you know, supplementing and then testing again and seeing if you're getting your index up to 8%. And then magnesium, we talked about, you know, getting, getting that RDA, hitting it with either, you know, increasing or a combination, ideally, increasing leafy greens and also taking a supplement, magnesium glycinate, citrate, malate are all pretty bioavailable sources of magnesium. Okay. So we're going to shift gears and we're going to get into the effortful part of this presentation, this talk.

This requires putting in the work, right? This isn't this isn't as simple as taking. taking a pill. But at the very least, I think that, you know, taking the pill is easier for a lot of people. But then there's the, of course, the people that want to go the step further and they're willing to put in the effort. So let's talk about that. We're going to talk about why I'm convinced that vigorous exercise is the most powerful longevity drug that you're going to get more than metformin, more than rapamycin, more than any of those things. If you could pill up what you can do with vigorous exercise, then I think that is like right now the best longevity drug we have for delaying the aging process and improving health span and improving lifespan. So when I say vigorous exercise, what do I mean? Generally speaking, of course, there's a sliding scale here because you can take someone who's completely sedentary and never really done any aerobic exercise.

vigorous exercise for them is going to be probably more what light to moderate exercise is for people that are physically active. But generally speaking, once you kind of adapt and get, you know, used to being physically active, vigorous exercise is about getting to 80% your max heart rate or estimated max heart rate. That's really what I'm talking about, 75 to 80% of your maximum heart rate. So cardio-respatory fitness, This is one of the best biomarkers for longevity, in my opinion. So cardio-respotory fitness is measured empirically by VO-2-max. So that's the maximal amount of oxygen that you can take up during maximal exercise. So when I use VO-2-max, sometimes these are like interchangeable,

cardiorespiratory fitness, B-O-2 max. I kind of use them interchangeably in this talk. But V-O-2-Mex is just directly measuring cardiorespiratory fitness. So cardio-respatory fitness is associated with improved longevity. It does improve longevity. And the biggest improvements you're going to get is if you're going from low normal, so for your age group, for your gender, if you're low normal, and going anywhere above that is where you get the biggest bang for your buck.

So people that have a low normal VO2 max, if they just go up to a, if they're below normal, and they go up to just low normal, they get about a 2.1 increased life expectancy. If they're below normal and they go up to high normal, they get almost a three-year increased life expectancy. And then if they go from below normal to the upper amount of normal, so this is the top 5% of the population, this is more like you're getting into the elite athlete level. That's associated with almost a five-year increase in life expectancy. So just to give you some perspective here, about half of the U.S. population is they have a low normal cardio respiratory fitness, and the other half has about a high normal

cardiorespiratory fitness. So again, just mostly having to do with being physically active or not being physically active. And on average, for every unit increase in VO2 max, it's associated with a 45-day increase in life expectancy. And there was a really important study published in JAMA back in 2018 that I'd just like to mention because it's, it's associated with a 45-day increase in life expectancy. it kind of established that there was no upper limit to the mortality reduction of having a high cardiorespiratory fitness. I mean, obviously within human, normal human life expectancy ranges, right? So people that were in the bottom 25% of cardio respiratory fitness or their VO2 max. And also, I like these studies because they're measuring something empirically.

I'm talking about VO2 max, right? This is a fitness test that's done. It's measured. It's empirical. versus a lot of studies in conflicting data out there when you have these questionnaires. How physically active are you? And you think about your last week or month. And then that's like you extrapolate it out. And they go, okay, well, based on this last week, this is how physically active we think this person is

over their lifetime or whatever. And I just, it's not a very, you know, it's all we have in some respects. But if you can measure something empirically, it's going to really help clear up a lot of the confounding and a lot of the, you know, conflicting data that you see out there. So I really like studies that measure VO2 max because it's something that's actually empirical rather than going off a questionnaire, right? With that's, those have all sorts of problems. So going from the low bottom 25% of the O2 max up to the elite level, so you're talking about the top 2.3%.

I mean, these are the elite athletes. That's associated with an 80% reduction in all cores, all. cause mortality. So comparing those two groups, people in the low 25% group versus the like the elite level. But even going from the high cardio respiratory fitness, so this is the top 25% of the population, they're good. I mean, these are people that are, they're committed exercises. They're really, they're physically active. They, if they go up to the elite level, they get a, you know, even 20% more reduction in all cause mortality. So if you compare the elite to the high cardiac fitness, you're still getting a 20% lower all-cause mortality by just moving up to that elite level.

And what was really interesting about this study was that being in that low 25% group, that they're in the bottom 25% for VO2 max, that was comparable to either same risk or greater risk than for mortality, early mortality, as type 2 diabetes, as smoking, and as smoking, and as having heart disease. So again, putting that into perspective, you know, we all think about these diseases and how they're, you know, they're, you know, increasing our early mortality risk, but like just not having a good cardio-respatory fitness can do the same thing. So how do you improve your VO2 max?

How do you improve your cardio-respatory fitness? Well, any exercise, any aerobic exercise is obviously going to be good for small changes in cardio-respatory fitness. But in particular, there have been meta-analysis that have found that vigorous intensity exercise, as they mentioned, and particularly high-intensity interval training, which we're going to talk about. So this is where you're doing sort of short bursts of, you know, very vigorous exercise. You're at least at 80% max heart rate, sometimes going even above that, and then having rest periods and you're doing those intervals. And why that's important is because there have been some studies that have found that even people that are meeting the guidelines,

lines for moderate aerobic exercise. So they're doing two and a half hours of moderate intensity aerobic exercise per week. About 40% of those people do not respond. In other words, they do not get VO2 max improvements. They are not improving their cardiorespiratory fitness by doing two and a half hours of moderate intensity exercise every week. And it's not really known why exactly there's these non-responder effect, but that's large percent of the population. However, when those people do more of a high-intensity interval training workout, they do more vigorous exercise, they start to respond and improve their VO-2 max. And it's thought because, you know, VO2 max, cardio-respatory fitness, to get those changes,

to get those improvements, you really have to increase cardiac output. So the stronger the signal, the more intense, the signal, the adaptations are greater. So your body responds by improving the delivery of oxygen to your tissues, right? So that's essentially what you're wanting to improve your cardiorespiratory fitness. And so it's kind of thought why vigorous intensity and particularly high-intensity and high-intensity interval training is so important for improving cardiorespiratory fitness. And one of the, there's been several studies looking at this. And for example, Dr. Martin Gabala out of McMaster University over in Ontario, Canada,

has done a lot of studies looking at different high-intensity interval training protocols. and it really seems if you're really wanting to improve that cardio respiratory fitness, that you have to do longer intervals, so three to five minute intervals of just the maximum intensity that you can maintain for that three to five minutes. And so a really good and well studied a lot of evidence on the Norwegian four by four protocol. So this is four minutes of the highest intensity that you can do. And then it's three minutes of recovery. So you're really going down to like light, light exercise. You want your heart. rate to go down, you want to sort of really give yourself some rest so that you can do it again.

So you repeat this four times, that's why it's called four by four. And this is one of the best protocols for improving VO2 max. If you don't want to go into a lab to get your VO2 max measured or you don't have access to it for whatever reason, one of the best evidence-based ways of measuring VO2 max at home, so to speak, not necessarily home, is what's called the 12-minute run test or walk test depending on your fitness level. Essentially, you need some sort of, you know, wearable device that can track your, your distance. So Apple Watch, your Fitbit, whatever. And you need to have like a flat surface that you can run on. So like a track field. And you want to run for 12 minutes or walk, depending on your fitness level, the maximum intensity that you can maintain for that

12 minutes. And basically your distance is going to be covered. And then you look up this equation and it converts, you know, your VO2 max based on that distance. And the reason you don't want hills and stuff is because that'll make you run, you know, the distance will be less. So you want to make sure you're giving yourself a flat surface so that you actually are more accurate in terms what your distance is during that 12-minute run test. This study out of UT Southwest in Dallas by Dr. Ben Levine

was really what has convinced me that vigorous, exercise is extremely important for the heart and the way the heart ages. So I mentioned cardiovascular disease. I mean, that's the number one killer in developed countries, right? So as we age, our heart undergoes certain inevitable changes. It gets smaller, it shrinks, it gets stiffer, less flexible. And this affects a lot of things that affects our cardiovascular disease risk. It affects our cardiovascular fitness, the ability for us to do aerobic exercise. And so what Ben did in this study, Dr. Levine did in this study, was really remarkable. He took a cohort of participants that were 50 years old on average.

And these were sedentary individuals that were otherwise healthy. So they didn't have any type 2 diabetes, hypertension, etc. They were quote unquote healthy, but they were sedentary. And he separated them into two groups. So the first group was the control group who did sort of stretching and yoga, for two years. And then the second group was the exercise intervention group. So these are the people that were going to be doing the exercise. And it ended up being a vigorous exercise protocol, but because there were sedentaries started out sort of lower to moderate intensity. And by the time it was six

months, these individuals are doing five to six hours a week of aerobic exercise with a large percentage of that time being in what's called the maximal steady state. So that's what I'm talking about when you're going as hard as you can, and you maintain that for about 20 or 30 minutes. So it's usually around 75, 80% max heart rate, and you're doing that for about 20 and 30 minutes. They also did the Norwegian 4x4 protocol once a week. And after two years, they essentially reverse these structural changes in their aging heart by like 20 years. So their hearts were essentially looking more like a 30-year-old heart after that two years of vigorous intensity exercise.

Now, like I mentioned, they were doing five to six hours a week of vigorous, a large portion of it in vigorous exercise. But it's simply astonishing, you know, the structural changes that they found. So there was more than 25% improvement in the elasticity of the heart after those two years, particularly in the left ventricular muscle of the heart. Of course, they did increase their VO2 max by about 20%, 20% as well. So it's just quite astounding. you can take a 50-year-old, put them on a pretty intense exercise program for two years,

and essentially reverse a lot of the structural changes that happen, you know, with the heart, with the aging process. Blood pressure improvements are also, you know, for people that are willing to put in the effort most of the time, I mean, there's always non-responders, but they can have drug-sized effects. In other words, they can be comparable to some drugs that are given to reduce hypertension. So there's been an analysis of 24 different randomized controlled trials found that six weeks of a pretty, you know, moderate to vigorous intensity exercise, 20 to 60 minutes of that three to four days a week, like had almost drug size effects in reducing blood pressure. So, you know, hypertension is not only a risk factor for cardiovascular disease. It's also a very, very important risk factor for dementia. and Alzheimer's disease. So there's every reason to want to not have hypertension. And 20% of

young people aged, you know, 18 to 39 have hypertension. And then half the, you know, about half the U.S. population of, you know, older adults have have hypertension. So it's a very common, you know, thing that, again, can be modified to quite a bit of an extent with aerobic exercise, particularly vigorous intensity exercise. Let's talk a little bit about on the molecular level why I'm talking about vigorous exercise and really that 80% max heart rate. It has to do with the fact that you are pushing, when you push your muscles to work harder than the oxygen can get to them to make energy, they shift to from using mitochondria and using oxygen for energy to using glucose through glycolysis. and it's a quick process that doesn't require oxygen.

It makes lactate as a byproduct, only it's not a byproduct. We often thought about it as a metabolic byproduct, but it's so much more than that. So lactate generated from muscles is what, it's an extracine, it's a myokine, and it's a stiggling molecule. It gets into circulation, and it is consumed by the brain. It's consumed by the heart, by the liver. liver, also by the muscle. It's consumed as a very easily utilizable source of energy, but also as a signaling molecule, as we'll talk about. And this is called a lactate shuttle.

It was pioneered by Dr. George Brooks at, out of UC Berkeley. And when I say a stiggling molecule, it's a way for your muscles to directly communicate with other parts of the body, like the brain. And so lactate itself has been shown to be responsible for increasing brain-derived neurotrophic factor, both in the plasma. This is in human studies, humans that exercise. Lactate correlates with the BDNF activation in plasma. BDNF can cross over the blood brain barrier, but also animal studies showing that it directly increases brain-derived neurotrophic factor in the brain. So BDNF is a very important neurotrophic factor. It's responsible for neuroplasticity. So that's the ability of your your brain, your neurons in your brain to adapt to changing environment. It's very important during the

aging process. You know, as things are, you know, changing and stuff, you want your brain to adapt to those changes. It's also important for depression. People with depression don't often adapt to the changing environment, and it is partly responsible for some of the depressive symptoms. But the brain-draved neurotrophic factor also is important for neurogenesis, the increase of new neurons, particularly in some brain regions like the hippocampus, which is involved in learning and memory. It helps, you know, existing neurons survive. There have been animal studies that have shown that when you induce them to do exercise and they get those learning and memory improvements that have also been found in human studies, that if you give them a drug and block brain-derived

neurotrophic factor, they don't get those learning and memory benefits. So really seems as though brain-driven neurotrophic factor is important to get those learning, those learning and memory benefits from exercise. And again, lactate is a key signaling molecule that increases brain-driven neurotrophic factor. Lactate is generated from your exercising muscles when you're forcing them to work hard. This isn't just going on a brisk walk. This is really getting your heart rate up, sweating, getting flush in the face. Lactate is also a singling molecule to increase neurotransmitters in the brain. This has been shown in both human studies and animal studies. So it's important for the production of serotonin. So studies have found that

people that exercise produce a lot of lactate. This correlates with an increase in serotonin, which also correlated with improved impulse control. Serotonin plays an important role in many neurological processes, including impulse control. So they're being able to have this inhibitory effect, which also plays a role in focus in attention. Noropenephrine is another one that's been shown. So as we're exercising really hard, our muscles are working harder. Our heart is working harder, but our brain is also working harder. And there have been human studies out of, I believe it's Norway that I found that the lactate produced during vigorous intensity exercise crosses the blood brain barrier is consumed by the brain. And this correlates with a burst

of norophenepinephrine production, which fuels the brain to work harder during exercise. It's also important for focus and attention and some of those effects that you get after after you do like a vigorous intensity workout. So there's some protocols that have been shown to maximize brain-derived neurotrophic factor in humans and some of these have also correlated with lactate levels. It seems as though like the best is getting the best of both the world. So you want vigorous intensity, about 80% max heart rate,

but you also want duration. So you want to get like 30 to 40 minutes of that is the most robust at increasing brain-driven neurotrophic factor. as measured in plasma and people, but 20 minutes will also increase it as well. Just 30 to 40 minutes does it even more. There's also some protocols that are more high-intensity interval training, so doing six rounds of 40-second intervals where you're going as hard as you can for 40 seconds, followed by a recovery period, also really increases brain-derived neurotrophic factor.

In fact, it increases it four to five times more in people compared to individuals that are doing about an hour and a half of more lower intensity cycling at about 25% their VO2 max peak. I want to just shift gears for a minute and talk about some of the anti-cancer effects of vigorous intensity exercise, you know, independent of the immune system. So the immune system, exercise activates the immune system. There's a robust effect on a variety of, you know, anti-metastatic effects there. but just the mechanical force of blood flow, blood flow actually affects what are called circulating tumor cells. So circulating tumor cells, escape from the primary side of the tumor, get into circulation, eventually travel to distant sites, and then they take residence and establish a new tumor elsewhere.

So this is metastasis. So circulating tumor cells, you obviously do not want to have them in circulation because they can play a role in metastasis. well, the shearing forces of blood flow itself can kill these circulating tumor cells because on every cell surface we have a mechanico, we have these mechanoreceptors that respond to movement, and cancer cells are all wonky and disrupted and messed up, and so they just can't handle that movement, and they die. So the more intense, the exercise, the more the greater the blood flow, the higher proportion of circulating tumor cells that are, the more, the more, the more that are actually undergo apoptosis and die.

There have been some studies looking at people that undergo about six months of aerobic exercise, anywhere between 50 to 70 percent max heart rate for 150 minutes a week. That significantly reduces the circulating tumor cells in people with anywhere between stage one to stage three, colon cancer. Other studies have found and correlated that circulating tumor cells are linked to a three times higher risk of cancer recurrence and a four times higher risk of cancer mortality in people with cancer. Also, stage three colon cancer patients that engage in aerobic exercise have a 40% reduction in cancer recurrence and a 63% reduction in cancer mortality.

So exercise plays a very important role in cancer metastasis and also in helping as an adjunct therapy to treating cancer as well. But you don't have to do the four. minutes of, you know, vigorous intensity of exercise, you know, every day to get benefits. So there's something called exercise snacks. These are very short and we're between one to three minute bursts of intense exercise. You're getting your heart rate up, 75, 80, 90% max heart rate. You can be doing anything from jumping jacks to, you know, sprinting stairs to high knees, to air squats. You know, there's a lot of ways to do it. And you do it just in a short burst. So it's a really great way to break up, you know, the workday.

It's also a really great way to improve metabolic health, particularly when you time it around meals, which we'll talk about in the minute. And the way it does that partly, well, there's a lot of mechanisms that play. But one of them, again, comes back to lactate being generated, you know, very acutely from exercising muscle, which then causes glucose transporters on the muscle surface to translocate to the muscle surface. So these are glute four transporters. then allow glucose circulating in circulation to them being taken up into muscle, therefore improving your blood glucose levels, and it also improves insulin sensitivity as well. When they're timed around

meal time, anywhere between 30 minutes to an hour, dramatically has an effect on blood glucose levels and insulin sensitivity, particularly in people with metabolic syndrome, type 2 diabetes. So it's a great way also. You just get up, do some high knees for a minute, or, you know, jumping jacks, or do something, that you can do quickly to get that exercise snack in. And another way it's approving metabolic health, I'll just mention briefly because we're running out of time, is through improving mitochondrial biogenesis, the generation of new, healthy young mitochondria. It's been trying to do this in muscle cells, and this is also happening through lactate. Lactate is a signaling molecule, yet again, increasing the expression of a very important protein

involved in mitochondrial biogenesis called PGC1 alpha. And so it plays an important role on increasing new mitochondria in muscle. This has been shown in human studies, but also animal studies have found that exercise increases lactate, which crosses the blood brain barrier and gets into the brain and increases mitochondrial biogenesis in the hippocampus and neurons in the hippocampus. So mitochondria in neurons and the hippocampus are being increased. I don't know why that mechanism wouldn't be conserved in humans. So, you know, the fact that it's happening in animals is also encouraging.

But exercise snacks are also associated with improved longevity. So I was talking about this sort of deliberate form of exercise snacks where you're doing high knees or jumping jacks. Well, there's large studies that have been underway and been published and there's ongoing studies looking at vigorous, intermittent lifestyle activity. So it's a type of exercise snack where you use everyday life situations to get your heart. heart rate up high for a minute or two minutes or three minutes. For example, you have to take the stairs every day to get to work. Well, instead of walking up the stairs, you sprint. So people are wearing these accelerometers, and, you know, so their heart rate is being measured and, you know, scientists have been able to gather all this data, and they found a people that have engaged in one to

two minutes, a vigorous intermittent activity three times a day, have a 40% reduction in all cause and in cancer mortality and a 50% reduction in cardiovascular related mortality. This is compared to non-exercisers. Now also people that even identify themselves as non-exercisors, so they're doing this in this vigorous stair climbing and stuff, but they don't actually go to the gym or do any leisure time activity. They still get these improvements. So it's a really great way to break up sedentary time. Being sedentary itself is an independent risk factor for all-cause mortality, cancer mortality. So in where it's just periods of when we're sitting like now is a risk factor even if you you're going to go to the gym you know later today so breaking up sedentary time is really important there's a lot of

ways to break up your sedentary time and I think that these exercise snacks are a great way to do it you just get up and you do high knees for one minute two minutes three minutes and I really kind of wanted to just have everyone do it for 30 seconds if we could do that real quick and then ending my talk So if you guys could just get up and we're going to do high knees right now. So that is where you try to get your leg as high as you can and you do the opposite hand up. And then we're going to just do it. We're just do it for 30 seconds. But really try to do it as hard as you can.

If you're wearing heels, take them off. You ready? Set. Go. All right. Get your heart right up. You really want to get your heart right up. They go fast. Now remember, we're doing 30 seconds. And I said, one, two minutes.

You do this. You're actually going to be tired. You're probably like, oh my gosh, is it not up yet? All right, we're only going to do 30 seconds because of time. All right, time. But as you can see, it works, right? So maybe we get a little more brain-dry neurotropic factor, a little more attentive for the next talk.

And I just want to close by saying, yeah, we've talked a lot about vigorous intensity exercise. But the reality is that any exercise you can do to form a habit, that you can do on a daily basis, if it's not vigorous intensity, any kind of exercise is beneficial. So keep that in mind. I was kind of going for the top here, like you want to reach for the stars. But really what you want to do is a form of habit. So that's the most important thing.

With that said, we talked about a lot today. I think I've covered a lot of the summaries, avoiding micronutrient insufficiencies, addressing the lack of, you know, vigorous intensity exercise. But again, forming that habit, do what you can do. I think I've been you guys on tools here to measure things, try to implement some Norwegian 4x4, which is brutal. Or just do exercise next. You guys, tell the next, you know, speaker, you know, in a couple of hours.

We've got to get up and get our blood flow higher, heart rate up. And with that, thank you so much for listening today. Hope you guys learn something. As we conclude today's exploration into the realms of cognitive enhancement and the science of longevity, I hope you've gained valuable insights that not only peak your interest, but also motivate you towards actionable steps. In line with today's discussions, as mentioned at the start of this episode, I have worked with my team to meticulously develop a guide that serves as a practical extension of our conversation.

This resource is centered around the critical role of brain-derived neurotrophic factor, or BDNF, a key player in your brain's ability to adapt, learn, and even regenerate. It's about turning the science of neuroplasticity into tangible practices that can significantly impact your cognitive function and decelerate the aging process of your brain. This guide takes a deep dive into specific lifestyle adjustments focusing on exercise, nutrition, and beyond that have been shown to boost BDNF levels and in turn cognitive health. It also includes a special segment, Ronda's Protocols, where I share both my personal experimentation and science-backed strategies aimed at enhancing cognitive performance and longevity.

These are not just guidelines, but a framework for integrating these practices into your life tailored to foster significant cognitive improvements. For those ready to translate today's insights into action, I invite you to download this guide at BDNF Protocols.com. It's crafted for anyone passionate about leveraging science to enhance cognition and to use a handful of key lifestyle tactics to meaningfully impact brain aging and improve the quality of cognition today. Once again, you can find this protocols guide at BDNF protocols.com.

Thank you so much for listening and I'll talk to you guys soon.