Dr. Rhonda Patrick: Optimizing Longevity with Micronutrients & Vigorous Exercise

People in the low cardio-respiratory fitness group had a mortality risk that was either comparable or worse than smoking, having type 2 diabetes, having cardiovascular disease, right? All these things that we know are terrible. Well, guess what? Being sedentary, being physically inactive is a disease. Smokers with a high omega-3 index had the same life expectancy as non-smokers with a low omega-3 index. So, in other words, not getting enough omega-3 was like smoking for life expectancy. It reduced their brain aging in the way such that it was like 2 years reduced brain aging. That is huge from Centrum Silver. Taking out just putting one pill in your mouth every day, right? So, today we're going to talk about some of my favorites, I would say. It's the the things that I think can have a very robust effect with little effort. And then we're going to talk about some of the things that require more effort to really improve the way we age, uh our quality of life, and our life expectancy. So, just to kind of give you a heads-up on what's coming up. We're going to talk about vitamin D, omega-3, and a simple multivitamin. I think these are what I call the low-hanging fruits in terms of just easy things that we can do to dramatically have an outsized effect on our health. I'm going to talk a little bit about increasing phytonutrient intake, and specifically we're going to focus on sulforaphane, and why I think that's very important for chemoprevention and detoxification. And then we're going to get into exercise, and specifically talk about vigorous-intensity exercise, and why vigorous-intensity exercise is important for cardiovascular health, reversing heart aging, and for the brain. So, let's just get in it, and talk about like the first part of the talk, which is really optimizing the micronutrient intake, and like I said, we're going to talk about vitamin D and omega-3 fatty acids, and we're actually going to talk about a multivitamin instead of magnesium today. And I I I know a lot of you here are practitioners, and are pretty familiar with why vitamin D is so important. But for those of you that don't realize, vitamin D is so much more than a vitamin. It's actually converted into a steroid hormone. That means that it goes into the nucleus of our cells, and interacts with our DNA, and it activates genes that are important, and it deactivates genes that are important for uh in terms of the timing of this activation and deactivation. We know that vitamin D controls about 5% of the protein-encoding human genome. It's over 1,000 genes. And it's very important to talk about this because of the widespread vitamin D insufficiency and deficiency. In fact, about 30% of the population is considered deficient. So, that would be if you have your vitamin D levels measured in the form of 25-hydroxy vitamin D, which is the major circulating form of vitamin D. About um 30% of the population has levels of 20 ng/mL or below. That's deficient. And then the other 40% has levels which is considered insufficient. So, that would be 30 ng/mL or below. And so, that's a huge part of the population that is just walking around vitamin D deficient, doesn't really know they are, and there's a simple solution, and that's why I like to talk about it, and that solution is actually taking a vitamin D supplement. In fact, 4,000 IUs a day really can correct a lot of vitamin D deficiency. Not all, but a lot. Um why vitamin D deficiency is so prevalent, many of you may already know this. We make vitamin D3 in our skin upon UVB radiation. So, that means that anything that blocks out the ability of UVB radiation to produce or to actually hit our skin is going to blunt vitamin D production. So, that means sunscreen, it means melanin, that's the dark pigmentation that is protects us from the burning rays of the sun. It also means depending on where we live and the time of year. So, more northern latitudes, at certain times of the year, UVB rays are not even reaching the atmosphere. So, if you're in a more northern latitude than, you know, 5 months out of the year, you're not even getting that UVB radiation. And then there's also age. As you get older, you're less able to make as much vitamin D3 from UVB radiation, and so that's a factor. And then also um body fat is another factor. So, as body fat goes up, vitamin D, which is a fat-soluble vitamin, bioavailability goes down. In fact, there have been studies that have shown that about 50% of the vitamin D bioavailability is reduced in people that are overweight and obese. So, you're just not able to release vitamin D into the bloodstream to be converted into the active steroid hormone where it's going to change and regulate genes if you're uh overweight or obese. And I like to start about I like to start talking about vitamin D in its role in aging by showing you this slide, which is a slide with rodents, and clearly people are not rodents, and there's a a lot of differences between us. But I think it's an important place to start because it really is visually highlights how important role vitamin D plays in the way we age. So, the two mice on the top, um they're 4 months of age. The the mouse that's on the left side here is a vitamin D receptor knockout animal. That means that its vitamin D receptor is knocked out, and so the action of vitamin D, you know, the hormonal function of vitamin D is not functioning. Um the mouse on the right is just a normal wild-type mouse. And then if if you look at the bottom panel, those are the same mice 4 months later. So, they're about 8 8 and 1/2 months of age. The vitamin D receptor knockout mouse is a progeria-type of aging model. So, it's accelerated aging. Um its organs are aging faster, its skin is aging faster, the hair is falling out, um bones are brittle. So, like pretty much every organ system is aging at a more rapid rate. And it's not a surprise because vitamin D is affecting, like I said, over 1,000 genes, you know, genes that are obviously involved in bone homeostasis, but also immune function, bone um brain function, just a lot of different processes that are important for regulating the aging process. And we know in humans, if we look at what's called Mendelian randomization. So, there have many, many studies that have measured vitamin D levels in people, and correlated that with a higher all-cause mortality. However, there's always the argument of, well, you're just looking at, you know, people that are sick and not going outside and exercising as much, and so therefore their vitamin D levels are low, and vitamin low vitamin D is just bio- biomarking, you know, disease. And so, that's where Mendelian randomization comes in, where we can actually use genetics to look at a specific environmental factor, and how it affects an outcome. So, in this case, we have genes that convert vitamin D3 into the active steroid hormone. And so, we can look at people. There are people that actually have single nucleotide polymorphisms in in those genes where they're not working as effectively, and therefore people are actually they have lower levels of either the stable circulating form of vitamin D, which is 25-hydroxy vitamin D, or the active steroid hormone, which is 1,25-hydroxy vitamin D. And we know that people with those genes, their they have genetically low levels of vitamin D, they have a higher all-cause mortality than people that don't have those genes. They they also have a higher respiratory-related mortality, and they have a higher cancer-related mortality. And so, that that data really I think strengthens a lot of the observational data that shows the same thing, of course, that you have you can never prove causation, and this is more of a way to look at actual causation because we're looking at these genes that are randomly, you know, distributed among the population, and those people with the low vitamin D have a higher all-cause mortality. There have also been a variety of studies. This is just one that I'm showing you here, um that have come out over the years showing that people that are deficient in vitamin D, they have low levels of vitamin D, they have accelerated epigenetic aging. So, if you look at the DNA, and you look at um these methylation groups that are kind of sitting on top of DNA, there's a pattern of these methylation groups as we age. And uh you know, Dr. Steve Horvath developed the first epigenetic clock uh that was really able to to to to categorize this aging. But um there's been subsequent clocks developed since that clock with also, you know, Dr. Steve Horvath and others um looking at actually your biological age. And so, you can look at your biological age, and it kind of gives you an idea of how well your body's aging. I I would say it's one of the factors. It's not my favorite, but it's one. So, people with vitamin D deficiency have accelerated epigenetic aging. If they take vitamin D in this in this case, in these people were African-American, and they were obese. They were two compounding effects in terms of causing their vitamin D deficiency. They were severely deficient. And they were given 4,000 IUs of vitamin D per day for about a month, and that reversed their epigenetic age by almost 2 years. So, essentially avoiding vitamin D deficiency is very important, and even if you are vitamin D deficient, you can get back to a sufficient level by supplementing, and that may improve your biological age, um at least in terms of what was the damage that was caused by for vitamin D deficiency. We also know that vitamin D deficiency has a pretty profound effect on the brain. We know that vitamin D activates klotho. This is one of the genes that it activates. Klotho is very important for brain function, cognitive function. It's associated with longevity and it's also associated with protecting against Alzheimer's disease. There've been a variety of studies done looking at vitamin D deficiency and dementia. Same problem as before, correlation doesn't equal causation. There've been studies linking about, you know, vitamin D deficiency with an 80% increased risk of dementia. If we turn to the Mendelian randomization studies again, just looking at genetically low vitamin D, we do see that there's about a 50% increased dementia risk. So, clearly there's something going on here with vitamin D deficiencies deficiency increasing dementia risk. And then on the flip side of that, there have also been studies that have shown people that supplement with vitamin D are about 40% less likely to get dementia. So, it decreases dementia risk by 40%. And that's what you want to see. You want to see that these studies are kind of all pointing in the right direction, whether we're talking about deficiency increasing the risk or supplementation decreasing the risk or the genetic component where it's a genes that are causing to deficiency are also doing the same thing as people that are getting their blood levels measured, right? And so, I think that um the the link between vitamin D deficient and dementia um is pretty solid, especially when we look at some of the structural changes that happen with vitamin D deficiency. So, there have been studies looking at the white matter part of the brain and um the damage that's done to this white matter. Remember, the white matter of your brain is very important for the communication um between between the brain regions and uh vitamin D deficiency causes this what's called white matter hyperintensities. It's this type of damage in white matter that shows up as like a white spot on an fMRI. And it's in a dose-dependent manner. So, actually, if you increase your vitamin D levels in a dose-dependent manner, for every 10 nanomoles per liter, I know I switched units, but this was like a UK study where their units are different, for every 10 nanomoles per liter increase in vitamin D levels, there was a decrease in the damage to their to the white matter part of the brain. So, this is also, I think, another important part of the story here where you're you know, vitamin D deficiency is affecting the brain. It's, you know, playing a role in brain aging, it's increasing dementia risk. And there's also evidence from randomized controlled trials that supplementing with vitamin D can actually improve cognitive function. Um there are two trials that I have here that I want to talk about. One was actually with Alzheimer's patients, so people that had Alzheimer's disease. And they were actually only given a pretty low dose of vitamin D. They were given about 800 IUs of vitamin D per day for 1 year. And that improved their cognitive performance, so memory, cognition. And it also reduced biomarkers of Alzheimer's disease, including the amyloid beta. They looked at their amyloid beta pathology as well. There was another study that was done in people with mild cognitive decline. Again, those individuals were given 800 IUs a day for about a year and that also and these are all both placebo-controlled studies. Um and the vitamin D also improved cognitive function in those individuals with mild cognitive decline. And this is just again a lower dose of vitamin D. So, I think that if you can get someone up to a more sufficient level, it it's not necessarily that vitamin D is a nootropic or is going to improve your brain function. It's you you want to correct deficiency. And I think that's the the key here. There's a lot of mechanisms by which vitamin D affects the brain. So, it plays a role in immune the immune modulation, the immune response. We could go on and on about that. It plays a role in neuroplasticity and also amyloid beta clearance, among other things. Um I mentioned it's over a thousand genes it's regulating. Many of those genes are in the brain. And there's really a simple solution here. And that is you have to get a blood test. And this is key, even if you're just taking a supplement, like you're taking let's say you're taking 4,000 IUs a day, you have to get a blood test because there are single nucleotide polymorphisms or variations in genes that affect people's ability to metabolize vitamin D3 and, you know, have it convert into this steroid hormone. Um and so, some people actually require a much higher dose and you'll never know that if you're supplementing with vitamin D and you don't get a blood test. So, blood test is the most important. And then the next thing that's pretty obvious would be supplementing to make sure you get to a sufficient level, which would be 30 nanograms per mil or more. I think the sweet spot that I've seen really is about thir- 30, if you you know, if you're if you're applying it safe, I like 40 nanograms per milliliter to about 60 or 70. Even can go up to 80. Uh you don't want to go too high, but I mean, that's a kind of a good sweet spot. If you're getting between 40 to 80 nanograms per milliliter. Okay. So, let's let's switch topics. Um I want to talk about omega-3 and this is a topic that's very I'm it's very important to me and I'm really obsessed with it. Like um the the uh person that introduced me mentioned that I am a associate scientist at the Fatty Acid Research Institute that was established by Dr. Bill Harris and I'm involved with research, particularly looking at how omega-3 fatty acids affect the brain. But I think it's really, really important uh to talk about because most people are not eating seafood or fish. I mean, it's like 90% of the global population does not eat enough omega-3 fatty acids or not getting enough omega-3 fatty acids from seafood. Um this is a this there was a Harvard study that was published a few years back that identified the top six preventable causes of death. So, in other words, things that are pretty preventable that will have a dramatic effect on your life expectancy. And there were things like avoiding hypertension, avoiding type 2 diabetes and cardiovascular disease, not smoking, right? Low omega-3 intake from seafood was on that top six list, along with the things I just mentioned. Uh there are three omega-3 fatty acids. The ones that are found in seafood are EPA and DHA. Those are the ones found in the marine sources. ALA is the plant source of omega-3. That was not part of the the equation here in term in terms of the one of the top six preventable causes of death. And like I said, most people are not eating enough seafood, they're not supplementing with omega-3. You can measure your omega-3 levels. The way to do that would be an omega-3 index test. You want to measure your omega-3 levels in red blood cells. That's because red blood cells take about 120 days to turn over, so they're more of a long-term marker of omega-3 versus just your plasma phospholipid. So, omega-3 index test is a a really good way to measure omega-3 levels. It was pioneered by Bill Harris and um one of his colleagues uh many years ago and I think it was back in 2004, about 20 years ago. And um they identified what's called the omega-3 index, high omega-3 index and a low omega-3 index. The high omega-3 index is like 8% or more and the low omega-3 index is 4% or lower. And what they've one of their first publications, what they found was that people with a high omega-3 index of 8% or more had a 90% lower risk of sudden cardiac death. Like 90% lower risk. That means like if you're having a heart attack, which happens like every 30 seconds in the United States, you're 90% less likely to die from that heart attack if you had a high omega-3 index. And you're also less likely to actually experience the heart attack. Um since then, Bill and his colleagues have published many different studies looking at different cohorts, whether it's the Framingham cohort or UK Biobank data, lots and lots of big cohort data out there. And I think the the message is clear. So, people with a high omega-3 index have about a five-year increased life expectancy compared to people with a low omega-3 index. And this is after correcting for all these confounding variables. Um we know that actually if you if you if you think about the average seafood intake in the US versus Japan, we know it's much higher in Japan. So, in Japan, their omega-3 index is about 10. Very high. In the US, our average omega-3 index is about five, 5%. So, we're on that like low low end. And Japan, they have about a five-year increased life expectancy than people in the US, on both the male and female side. Um within this Framingham data, what was so interesting to me was that, you know, Bill and his colleagues had plotted they'd looked at the omega-3 index and then they they looked at smokers versus non-smokers. And this is where it to me is so clear because we know that smoking one of the worst things you can do for your cardiovascular health and your heart is to smoke. Most people think about lung cancer. Forget lung cancer. That increase happens in a linear fashion, right? Your your lung cancer risk goes up like decades later. Cardiovascular disease happens like pretty quick. Um smoking is really bad for your heart. And we know that omega-3s are actually really good for your heart. And so, if if we if you look at the data here and I like people to kind of look at the the slide. The green curve is the life expectancy curve, the green one. Those are non-smokers with a high omega-3 index. If you look at the red curve, people with the lowest life expectancy, those were smokers with a low omega-3 index, right? Big surprise. But what the biggest surprise to me was that if you look at the orange and blue, they're pretty much perfectly overlaid. I mean, I can't imagine anything being more overlaid and more perfectly matching. >> [snorts] >> Smokers with a high omega-3 index had the same life expectancy as non-smokers with a low omega-3 index. So in other words, not getting enough omega-3 was like smoking for life expectancy. And that is just something that I think people should think about. I mean, obviously like smokers are like jumping up and down cuz they're like, "I can take a fish oil supplement and have the same, you know, be healthy." Um but really I think what we should be thinking about is that we're not eating enough seafood or supplementing with a high-quality fish oil supplement to get our omega-3 index to that 8% range. And we'll talk about what it takes to get there. But I think even stronger data uh we can turn to some of the large randomized controlled trials looking at supplementing with omega-3 fatty acids, whether it's the Vascepa, which is the purified EPA form in the Reduce-It trial where people were given I mean, we're talking large large um populations of people were given 4 g a day for was it 2 5 years and their cardiovascular disease risk and the risk of having a cardiovascular event, whether that was a heart attack or a stroke, that was reduced by 25% compared to placebo. And then there was the Strength study um that was actually stopped early because there was no benefit and the form that they were given these individuals was a free fatty acid form, so it wasn't esterified to anything, which can be very irritating on the gut. And then there was the VITAL study. In this study, people were given a kind of a low dose in my opinion. They were given about 840 mg of Lovaza. That's DHA and EPA combined. And and this was also a 5-year study. And the secondary outcomes, when you look at the secondary outcomes, the the the there was a reduced heart attack risk by almost 30%. Total coronary heart disease was reduced by 17%. Um and particularly people, this was happening in people that were having a low fish intake. So we have I think a lot of evidence that omega-3 is very important for cardiovascular health and it doesn't take a lot of omega-3. In fact, it only takes about two 1.5 to 2 g of a fish oil supplement per day to get someone from a low omega-3 index to a high omega-3 index. It's very achievable. Okay, and the last you know, like two slides, I want to just talk about a micronutrient in the form of a multivitamin because I think it's such a low-hanging fruit and it's and you know, I remember 10 years ago studies being published saying multivitamins are useless, they're expensive urine, it's not doing anything and anything it might even be harmful. Um it turns out that was, you know, completely wrong. We know that micronutrient deficiencies and insufficiencies are very common in the US from a lot of these large national surveys that have been done called NHANES studies. So you can see here, we talked about vitamin D, that's not from the diet, that's from sun exposure. The vitamin E, 60% of the US population is not getting enough vitamin E. I mean, 45% of the population is not getting enough magnesium. Calcium is 35%, vitamin A 35%. I mean, it just goes on and on. Omega-3, I mentioned 80 to 90%. So people are not getting enough of these essential micronutrients from their foods. I mean, these things are running our metabolism, they're cofactor for enzymes, they're doing a lot of important things, regulating inflammation, changing gene expression. And we don't think about them. We're so focused on macronutrients that we forget about the micronutrients and how important they are for the way we we know, regulating the way we age. And so I want to talk about the COSMOS studies. There was three trials that were done where older adults were given a daily multivitamin and and this was a very standard one run-of-the-mill multivitamin. You may have heard of Centrum Silver. I mean, it's like you can buy it in any CVS, Walmart, right? It's a it's not like a bougie type of multivitamin. They were given Centrum Silver for 2 years or a placebo. And it improved their cognitive function globally. So in fact, global cognitive function was improved by like 2 years. So it it reduced their brain aging in the way such that it was like 2 years reduced brain aging. That is huge from Centrum Silver taking it just putting one pill in your mouth every day, right? Um the what was so profound was the actually the effect on episodic memory. So that's the kind of memory, you know, where we remember events, people, things like that. Um that was improved. It was like reducing the aging of our episodic memory by almost 5 years. It's 4.8 years, which is just astronomical. Um from just taking a, you know, Centrum Silver every day. That's what I'm talking about. Like these micronutrients have effects on the way we're aging, on our brain, on our cognitive function. I mean, name a person in here that doesn't want to get their parents taking a multivitamin every day, right? It it's so easy. It's something they're going to do. They don't have to put a lot of effort in and there's outsized effects, right? So I think that's kind of the the wrap-up for my micronutrient part of this talk is that one, you want to avoid vitamin D deficiency by getting a blood test. We know that about 4,000 IUs a day in most people, 4,000 to 5,000 IUs a day can get people to a sufficient level. There are outlier cases that have to take much more and you won't know that unless you get the blood test. With the omega-3 index, I mean, I think it's pretty clear. You don't want to be smoking, right? I mean, your life expectancy, you don't want to be like a smoker that's taking a bunch of omega-3. Um it's it's so important for so many different processes. I mean, I I could spend like 2 hours talking about that, but I'm convinced that the data is clear. And when we're talking about going from a low omega-3 index to a high omega-3 index, we're not talking about a lot. 1.5 to 2 g of a high-quality fish oil supplement is easy to do. And then lastly, the multivitamin for brain brain aging, right? Easy. Super easy to do. Okay, so I want to get into this Oh my goodness, I've really gone over. I'm going to I'm going to blast through this part. Um sulforaphane really it's something that is found in cruciferous vegetables like broccoli. Um it's actually not in the vegetable itself. The precursor to it's in it, glucoraphanin. When the vegetable is crushed or like broken, it's converted the glucoraphanin is converted into sulforaphane. Um sulforaphane is the biggest dietary activator of our NRF2 system. NRF2 is activating hundreds of genes. Many of them are involved in chemo prevention, preventing cancer. They're involved in detoxification. So it activates our phase two detoxification enzymes so that we can detoxify environmental toxins that we're exposed to on a daily basis. It deactivates phase one biotrans biotransformation enzymes. These are enzymes that will convert a procarcinogen into a carcinogen. We actually are eating lots of these things all the time we don't even know it. Uh the procarcinogens. And um it also activates antioxidant and anti-inflammatory systems. It's very very powerful pathway and sulforaphane is one of the major dietary activators of it. Um this is just a mechanism by which it's activating it, which I don't think we need to go into. There have been human studies showing that sulforaphane does reduce DNA damage in people. So uh people that ate 85 g of watercress, that's a type of cruciferous vegetable per day for 8 weeks, lowered their oxidative DNA damage by like 24%. Broccoli, two 250 g a day, people that ate um broccoli for two 250 g of broccoli a day lowered their um oxidized DNA lesions by 41%. Brussels sprouts, 300 g a day, this lowered another marker of oxidative damage by about almost 30%. So again, um it's really it's DNA damage is the precursor to mutations that can lead to cancer, oncogenic mutations. So you want to lower that DNA damage cuz that's something that accumulates over time and eventually, you know, in your fifth, sixth, seventh decade of life, you get cancer. So it's really good if you can lower your oxidative DNA damage. There have also been studies looking at people given a sulforaphane extract and reducing the basically the toxic burden. So there have been a couple of studies done most of them are out of China where their air pollution is very very bad. Uh and so benzene is a is a component that's found in air pollution. It's also in cigarette smoke, wildfire smoke. It's a carcinogen. Uh and so in these studies, individuals were given benzene. They were given about 40 micromoles per day and it increased the excretion of benzene through their urine by about 60% within 24 hours. So it didn't take a long time to start to work. I was just in China. I got back 5 days ago. I mean, I was taking my sulforaphane while I was there the whole time. Um and there's multiple studies showing this. It increases the excretion of benzene and acrolein, that's another carcinogen. Acrolein is something that uh we're exposed to when we cook foods. So um sulforaphane is really important for increasing the excretion of these these toxic compounds. And then there have been studies looking at prostate cancer recurrence. So men with low-grade prostate cancer that were supplementing with about 60 mg of sulforaphane a day slowed the doubling of their PSA antigen, which is like the major biomarker that's used to sort of monitor prostate cancer progression. Um it was slowed by about 86%. And then there's some studies on UV, topically putting sulforaphane on skin and also uh, lowering the inflammation and and that sort of effect as well. There's a lot of preclinical evidence out there on sulforaphane protecting against cancer, whether it's prostate cancer, breast cancer, colon cancer. I mean, it just it go into the literature, preclinical data is endless. Very clear. You It's like you can't you can't argue that sulforaphane basically is lowering metastasis, it's lowering tumor burden. So, if you give, you know, mice, for example, breast cancer stem cells, it'll decrea- it can decrease their tumor growth by more than 50%. Um, so, there's just countless studies out there showing this. So, I think that the the take-home here is that eating cruciferous vegetables and adding them to your diet is important. Broccoli sprouts are the best source of sulforaphane. They're the young plant. In fact, there's about 100 times more of the precursor of sulforaphane, glucoraphanin, in broccoli sprouts compared to mature broccoli. So, um, broccoli sprouts are a great source of sulforaphane. About 45 to 100 g a day gets you about some of the doses that I talked about in these studies. If you're going to cook your broccoli, the enzyme that converts glucoraphanin into sulforaphane is heat sensitive. And so, you do you do get a little bit less bang for your buck than eating, like, for example, raw broccoli. Um, however, if you add mustard seed powder to your broccoli or to your brussels sprouts or to whatever, fill in the blank cruciferous vegetable that you're kind of lightly cooking, it can increase that uh, bioavailability. It basically helps it It's ad- adding an exogenous source of that enzyme, myrosinase, back to the broccoli. So, you're basically by fourfold getting more of that sulforaphane. So, that's also important. And then, there's supplements. You can actually find stabilized forms of sulforaphane out there, as well. Okay. I want to get to, like, my favorite part of the talk. And this is this is the effortful part. This is, like, exercise. There is absolutely nothing that I have found in all of my, you know, reading of the literature that is more powerful and potent at delaying every related aspect to aging and age-related disease than exercise. Um, particularly vigorous-intensity exercise. And when I say vigorous intensity, I mean the kind of exercises that you're doing and you really can't have a conversation. You can't really talk to someone while you're doing it because you're so out of breath while you're doing that exercise. Uh, for people that wear heart rate monitors, we're talking about 80-85% max heart rate. You're getting you're getting into that zone or more. That is vigorous-intensity exercise. And I want to start by talking about cardiorespiratory fitness, which is something that it is a marker of It's it's a marker of our our, I would say, life expectancy and mortality risk. Dare to say longevity. Uh, we know we know that eventually, you know, as we're aging, we're going on this cliff. Our our cardiorespiratory fitness is going down. And so, you want to get as high up as you can. You want to have the highest cardiorespiratory fitness as you can because that cliff will come. And the higher up you start, the longer it's going to take to get to that cliff. And so, VO2 max, the maximum amount of oxygen that you can take in during maximal exercise, is the way cardiorespiratory fitness is measured. We know that people that are have a low cardiorespiratory fitness, if they go anywhere above being like the low, like, let's say they go to just the low normal range, that's associated with just a 2-year increased life expectancy. If they go from like below low to more of a high, then that's like a 5-year increased life expectancy. And there's been some researchers out there that have that have calculated each unit increase in your VO2 max, in your cardiorespiratory fitness, is associated So, for each unit, which would be 1 ml per kilogram per minute, that correlates to about 45-day life extension. So, for each unit you're going up, you're about you're gaining about 45 days of life expectancy. There've been a a few studies now. One of them here, this is the JAMA one, um, that have shown people that are in the more elite level, like, the real high cardiorespiratory fitness, again, they've got a 5-year increased life expectancy, but they also have a 80% lower, uh, mortality risk than people in the low cardiorespiratory fitness group. Um, and what was interesting about this study is that even people with a high cardiorespiratory fitness, if you compared them to the elite, people in the elite group still had about a 20% lower mortality risk than people in the high. So, it just keeps going up. Uh, but what was so interesting to me about that study was that people in the low cardiorespiratory fitness group had a mortality risk that was either comparable or worse than smoking, having type 2 diabetes, having cardiovascular disease, right? All these things that we know are terrible. Well, guess what? Being sedentary, being physically inactive, is a disease. And we need to start treating it as a disease because it is a disease. So, that that basically the cardiorespiratory fitness was predicting, you know, mortality risk like these other diseases that people know about as being terrible, right? People don't talk about cardiorespiratory fitness being terrible. We know, um, and this kind of brings it back to vigorous exercise. There The question is, how do you improve your cardiorespiratory fitness? Well, any exercise is really, especially, you know, aerobic training, is really going to improve cardiorespiratory fitness. However, um, when you get to a certain point, you know, people that are even doing the physical activity guidelines, so, let's say they're doing like 2 and 1/2 hours per week of moderate-intensity you know, moderate-intensity physical activity. So, this would be the kind of exercise that you can maybe have a conversation sort of like you're breathy, but you can sort of talk. Right? You're not like so you're not like going all you're not really going that that hard. Um, you're still working, but not as hard as you would if you were doing more vigorous type of exercise. Um, about 40% of people that are doing that, 2 and 1/2 hours a week, cannot improve their cardiorespiratory fitness unless they engage in high-intensity interval training. Unless they mix in that vigorous-intensity exercise. And it's not really known why that is, um, but you know, at the end of the day, the challenge that you're putting on your cardiovascular system, on your lungs, your muscular system, your brain, everything that you're, you know, when you when you increase that challenge, like you do when you're engaging in vigorous-intensity exercise, the adaptations to that are also greater. And so, the adaptations being you can transport oxygen, you know, to throughout your system quicker, right? To bring it to your muscles faster. And so, and that's kind of the the thought right now is that's what's happening is that basically it's just the the stress when the stress is stronger, the adaptation is is also stronger. >> [clears throat] >> Uh, there's a variety of different protocols out there, high-intensity interval training protocols that can improve cardiorespiratory fitness. The longer the interval, the more robust the effect on improving cardiorespiratory fitness. So, high-intensity interval training is referring to these short bursts of like more vigorous-intensity exercise followed by, you know, like a more light exercise recovery. There's so many protocols out there, and honestly, all of them do improve cardiorespiratory fitness. If you're really wanting to like get an outsized effect, then you should going to start getting into the minutes-long interval. So, the Norwegian 4 by 4 is one I like to talk about because there's so many publications out there showing that it can improve cardiorespiratory fitness. So, that the Norwegian 4 by 4 was something that's practiced by these Norwegian skiing group. Essentially, they're doing 4-minute interval, and it's on a stationary bike, and they're going as hard as they can and maintain for that 4 minutes. So, they're not going all out cuz there's no way you can do that. But, they're just going as hard as they can to maintain for that 4 minutes. And then, they have a 3-minute recovery where they're going super super light. They're letting their heart rate come down to recover. And then, they go back at it again. So, that's repeated four times. It's a 4 by 4. That is a really good way to improve cardiorespiratory fitness, but it's not the only way. You can do a minute on, a minute off. You can do 30 seconds on, 20 seconds off. You can do 20 seconds on, 10 sec- Like, Tabatas. All these things do improve cardiorespiratory fitness. Um, it's just the the longer the And I do want to talk about uh, Dr. Ben Levine's study on reversing cardiac aging. So, the reason I like to talk about this study was because it included the Norwegian 4 by 4, and also included a lot of vigorous-intensity exercise. And essentially, um, Ben took about, you know, 50-year-olds that were sedentary, so, they weren't physically active, but they didn't have any other diseases, and put them on this intense training protocol for 2 years. It was progressive. They didn't just right out the gate start doing the Norwegian 4 by 4. They worked their way up, right? When you have someone that's not active, and then you're putting them on a on a pretty intense training protocol, you have to progressively get there. And so, by the end of like the first 6 months, people then started doing the Norwegian 4 by 4 once a week. They were doing 30 minutes of, I would say, you know, getting to that 75% max heart rate, um, zone for their their more vigorous, closer to vigorous-intensity exercise. They're doing it about three times a week. In total, they were they were working out about 5 hours a week. And a large portion of that was vigorous-intensity exercise. They also did a moderate-intensity exercise and a little bit of resistance training. The control group only did some kind of yoga- ish type of, you know, exercise. And after 2 years, their hearts were imaged compared to their baseline. So, as we age, our hearts are aging as well. And our hearts shrink with age, and they also get stiffer with age. And this affects our cardiovascular disease risk. It also affects the ability of our hearts to our, you know, being able to improve cardiorespiratory fitness. But it affects our cardiovascular disease risk. You don't want a stiff heart, and you don't want it to keep shrinking. And so what happened after the 2 years of that intense exercise protocol is these 50-year-olds reversed the aging of their heart by essentially 20 years. So their hearts grew, and they became more flexible, and they looked structurally, if you looked at them, by all the imaging techniques and all the probing probing and stuff that's done, they looked more like a 30-year-old's heart. And I'm very much glossing over a lot of this data, but essentially the important thing is that it's not too late to start working out, and it will have a profound effect if you put in the time and the effort on the way you're aging. Not only the way your heart is aging, but also the way your brain is aging. So we know exercise can immediately improve cognitive function, executive function. I mean, just a single 10-minute exercise bout can do that. I'm going to blast through some of these. It happens immediately. Your brain can be rewired. I mean, I I'm doing I'm a big fan of just doing 10 minutes like before any anything that you need to do. If you have to learn something, if you're, you know, giving a talk, whatever it is, exercise before you do it. It makes a big difference. Speeds up reaction time, improves a lot of executive function. A lot of that has to do with the fact that lactate is produced when you exercise intensely, when you work really hard, you're forcing your cells to make energy in a way that is producing lactate as a metabolic byproduct. Turns out it's not just a metabolic byproduct. In fact, lactate is a very important substrate not only to make energy, it's used it's actually energetically more favorable to use lactate than glucose to make energy. And lactate gets shuttled back into muscle and is used as energy. Um lactate's also shuttled to other parts of the body and most, I think, importantly, the brain, where it acts as a signaling molecule. In other words, it's a way for your muscles to communicate with other parts of your body like your brain and say, "Hey, I'm working hard here. We got to like respond to this work, right?" And part of the way that it responds is by increasing brain-derived neurotrophic factor, BDNF. Um brain-derived neurotrophic factor is so important for it helps grow new neurons. It is important for learning and memory, neuroplasticity. So that's the ability of your brain to adapt to changing environments. Uh very important. So brain-derived neurotrophic factor is something that I would say is a youthful elixir for your brain. And we know vigorous intensity exercise increases it through lactate. Lactate is that signaling molecule. Because when you're working out hard, your brain is also working hard. Your brain has to work hard when you're exercising hard. And this is an adaptation. This is the way the body is adapting to that hard exercise. Much like the improvements in cardiorespiratory fitness is the way your your cardiovascular system adapts. It also increases neurotransmitters. So there have been human studies that have found that they've looked at dose-dependent in terms of exercise, moderate, light, moderate, and vigorous intensity exercise. And they looked at serotonin levels. And the more vigorous intensity the exercise, the higher the serotonin levels are. Serotonin levels in the plasma do correlate with brain serotonin levels. And in fact, individuals that were doing the vigorous intensity exercise had higher serotonin, and they had more they had better impulse control. So they had basically improved what's called inhibitory control. We know that serotonin, most of us think of it as the the neurotransmitter that's involved in the way we feel, our mood. It's important for mood, but it's important for executive function, decision-making, and it's really important for impulse control. You can take someone and deplete their serotonin by giving them a a bunch of branch chain amino acids, which compete with tryptophan, which is the precursor to make serotonin. And within like an hour or two, their impulse control is just shot. So um it's very important for impulse control. It also increases norepinephrine. Norepinephrine is involved in focus and tension. Um so lactate again is the signaling molecule that is telling the brain to increase these neurotransmitters as a response to intense exercise, essentially. A lot of protocols out there for increasing BDNF, the Norwegian 4 by 4. Anything that's really going vigorous, you want to be about 80% your max heart rate. You want to go out If you're doing that for like 30 minutes, that's a really big boost in BDNF. But there's a lot of protocols out there that can increase brain-derived neurotrophic factor. Again, the lactate's the key. To get the lactate, you have to go harder. You have to get the vigorous intensity exercise. And there's also this I like to to talk about this PNAS study. It's a classic study published back in 2011, I think. And um it really showed that older adults that engaged in aerobic exercise that they were doing more like 70-75% of their max heart rate, which is pretty good for someone who's 65 or older, right? Um they did this exercise for 2 years, and they not only countered the brain atrophy that happens with age. So as we age, as we get to older adult older adulthood, we start to lose between 1 to 2% of our our hippocampal brain region atrophies per year. Um these older adults that were engaging in the physical activity, um like I said, close to vigorous intensity for that for that cohort, not only did they not experience that 1 to 2% brain atrophy in the hippocampal regions, they experienced growth. They experienced a 2% growth in their hippocampal region. So that's effectively restoring about 1 to 2 years of previous loss of their the hippocampal, you know, brain region. Again, brain-derived neurotrophic factor is responsible for the growth of new neurons, particularly in the hippocampal part of the brain. And they also had improvements in cognition that correlated as well with this increase in the hippocampal hippocampal part of the brain. And then I've got like hardly any time here. In fact, I'm already over. So I'm going to just tell you guys about exercise snacks cuz I think it's a wonderful thing. These are short bursts of intense exercise. You know, you're going you're going at 75-80% max heart rate. You can do anything from high knees to to bodyweight squats, jump, you know, jumping jacks, whatever your favorite burpees, whatever your favorite thing is to do. There have now been enough studies out there showing that exercise snacks can improve longevity. There have been like three studies that I at least know of that are pretty large studies where people are wearing accelerometers. Scientists can track their heart rate. And people that are doing these vigorous types of exercise snacks throughout the day, if they're doing it So it's between 1 to 2 minutes per bout, and they do it if they do it three times a day, they have a 40% reduction in cancer-related mortality, they have a 50% reduction in cardiovascular-related mortality, and a 40% reduction in all-cause mortality. So and this is even in people that identify themselves as non-exercisers. So they don't go to the gym. What they're doing is they're taking advantage of like everyday situations to get their heart rate up. So they use the stairs, and they don't just, you know, walk up it, they sprint up them. Um or they they bike to bike to work or go fast to work or whatever. Um briskly walk to work. They're doing these, you know, short bouts of exercise snacks. Now, I'm talking about these more structured types of snacks uh versus the the Vilpa, which is the kind that's vigorous intermittent lifestyle activity where these people are just doing taking advantage of everyday situations. They're not necessarily stopping and doing air squats, but there's there's I think every reason to do them. One, it's increasing blood flow to the brain. Um two, uh lactate gets produced immediately, and there've been studies showing that even just doing, you know, air squats throughout your work day can improve glucose regulation better than like a 30-minute walk. So for example, doing like, you know, 30 air squats every 45 minutes for a 8-hour work day was able to improve glucose regulation better than a 30-minute walk. So we're going to get up, and we're going to end with our with our exercise snack because you've all been sitting too long. And this is the best one like most fun part. We're going to do just a minute. I mean, we could do 2 minutes, but I think after 1 minute you'll be like, "Okay, we're done." Do you guys want to do high knees or air squats? Air squats? Okay. Dang, I just got back from China, and I did um I did my barbell squats like 2 days ago, and I am so sore, but I'm going to do them. All right. Okay. Wait a minute. Let me get the wrong one here. Ready? Here we go. And try to like put in some effort. Okay. Try to put in the effort, right? Like fast. Now, I'm able to talk. So it's not like super super vigorous, but I can also measure my heart rate and see. I see some people doing them. Come on. Like hurt? Are you burning? Okay, we're at 30 seconds. I know some of you hate me right now. Oh, whoops. Well, good thing we didn't do high knees. Okay, 10 seconds. Trying to go three, two, one. All right. I just want to see what my heart rate say my heart rate. Really? It's only 80? 145. Yeah. so exercise snacks. But don't you always feel good right now? Yes. Do them. Do them. Take a break every hour and do 1 minute of air squats. If you do that just three times. Right? Three a lot It's two The study was actually like 2 minutes. So, you have to do that for 2 minutes or just do 1 minute do six times a day, right? It's huge. It's having a huge effect. And so, with that that's my conclusion. Right? Avoid micronutrient deficiencies. Increase your sulfor- your sulforaphane cruciferous vegetables. And at the very least get some exercise snacks, but let's do some bigger intensity exercise, right? That's going to improve the way we age.