The Peter Attia Drive - #217 ‒ Exercise, VO2 max, and longevity | Mike Joyner, M.D.

Episode Date: August 8, 2022

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Mike Joyner is a physician-researcher and one of the world’s leading experts on human performance and exercise physiology. In this episode, Mike discusses how to combat age-related declines in health and fitness levels by using various modes of exercise to improve lifespan and healthspan. Mike explains the impact of exercise on the autonomic nervous system, blood pressure, heart rate, heart rate variability, heart rate recovery, and max heart rate. He dives deep into VO2 max, including how it’s measured, what is driving it, and how to improve it. Mike provides training insights for the average person, including training volume and exercise intensity as well as simple metrics to track. Furthermore, he gives his take on the theoretical “J-curve” relationship between exercise and longevity, as well as whether possible health dangers may be associated with excessive exercise. We discuss: Mike’s training as an anesthesiologist and interest in exercise physiology [2:30]; How exercise increases longevity [7:00]; The impressive data on the benefits of exercise [9:45]; The Centenarian Olympics and other ways to mitigate age-related decline in strength and stability [15:00]; The violent dropoff in strength and activity with age and how exercise preserves fitness in old age [19:00]; Benefits of exercise on mortality and fracture risk, and the interplay of nutrition and exercise [22:00]; How exercise benefits the autonomic nervous system and why this plays an important role in our health [26:30]; VO2 max, heart rate recovery, heart rate variability, and other metrics of fitness positively impacted by exercise [28:30]; Reduction in all-cause mortality with increased fitness levels and VO2 max [32:45]; Does the relationship between exercise and longevity follow a J-curve? [40:00]; Mitigating age-related decline in fitness by elevating your VO2 max at a young age [46:15]; Breaking down the variables that drive VO2 max [54:30]; Learning from elite athletes: Training regimens, aerobic efficiency, and other impressive metrics [1:00:15]; Health benefits of light exercise for the average person [1:09:00]; Simple training metrics to track, and Mike’s current exercise regimen [1:11:15]; How to boost your VO2 max, and the importance of form and tempo with interval training [1:18:15]; Training advice for the average person [1:25:15]; Why professional athletes have longer careers than they’ve had in the past [1:27:30]; Use of performance-enhancing drugs in professional sports [1:29:45]; Can the miracle of exercise be put in a pill? [1:36:00]; Mike’s current research and questions he’s most interested in answering [1:39:00]; Use of convalescent plasma to treat COVID-19 [1:41:15]; Parting thoughts on the current state of fitness and exercise in society [1:47:15]; More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Atia. This podcast, my website, and my weekly newsletter, I'll focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you want to take your knowledge of this space to the next level. At the end of this episode, I'll explain what those benefits are, or if you want to learn

more now, head over to peteratia MD dot com forward slash subscribe. Now, without further delay, here's today's episode. I guess this week is Mike Joyner. Now, Mike's someone I wanted to have on this podcast for quite some time, and I think I mentioned it in the podcast. Mike's someone whose research I've been reading personally for probably over 20 years. He's a physician researcher. He is a professor and vice chair for research in the Department of Anesthesia and Parioperative Care at the Mayo Clinic. He's co-authored over 250 journal articles and he's written numerous pieces all over the place, including in magazines that maybe some of you have read outside in sports illustrated.

He also has his own website titled Human Limits, which as the name suggests speaks to Mike's interest, which is really around the limits of human physiology. Now, his research background is in studying how the nervous system regulates vascular systems and blood flow, how age and sex, disease, states affect physiology, and understanding basically the limits of human physiology by studying elite athletes. In this episode, we talk mostly about exercise, and within that, we talk about how exercise helps us live longer, the importance of exercise as we age, and how exercise compares to nutrition in terms of the impact it can have in health. We talk about the impact of the autonomic nervous system, blood pressure, heart rate,

heart rate variability, heart rate recovery, and maximum heart rate. From there, we talk about VO2 max. We discuss how it's measured. We talk about what leads to the decline in VO2 max as we age. We spend some time talking about the J curvecurve as it pertains to over exercising, is it possible? What are the dangers of too much exercise? We speak about how one should partition their time between training at high intensity and low intensity, and we talk about a few other things like performance enhancing drugs and sports, and if there's ever going to be a drug that mimics the benefits of exercise. So without further delay, please enjoy my conversation with Mike Joyner. I'm not going to be a fan of Mike Joyner.

I'm not going to be a fan of Mike Joyner. It is such a pleasure to be at least virtually sitting here with you today. As I was kind of alluding to a moment ago, I were to sort of look at all the people I've had on this podcast so far and kind of ask the question, when was the first time I became familiar with their body of work?

You would be pretty far up there in terms of duration. So growing up endurance sports were always something that meant the world to me. And once I even made that decision to go to medical school, a big part of it at least was understanding physiology better. And so it's been 25 or 30 years that I've been reading your studies. In some ways, it's a long time coming to finally be sitting down with you and hope to meet you in person one day. Peter, thanks much and it's great to be able to chance to visit with you today. Thank you for inviting me and I'm glad somebody's been paying attention to what I've been doing

for the last 25 or 30 years. So it's very validating. Thank you. Let's talk a little bit about your background. You're a physician by training. I believe you're an anesthesiologist, correct? Correct. You decided in medical school, you wanted to anesthesia. You've always had a lifelong interest in exercise and exercise physiology. Did you just view anesthesia as the most logical conduit to better understand human physiology? Peter, before I went to medical school, I actually volunteered a subject peder before I went to medical school I actually volunteered subject in a study on the lactate threshold or anaerobic threshold when I was 19 at the University of Arizona and luckily there were ex-physiologists there but a couple of younger physicians came over from the med school and it became clear to me

when I was 19 or 20 that if I wanted to have a career as a research physiologist doing invasive studies, in other words, pretty catheters in people in humans, might be wise to go to medical school. So this was always sort of my vision starting to about age 20 or 21. And then what happened is I was thinking of going to cardiology or pulmonary medicine. I was working at the two-time VA at one time doing a surgery rotation and I saw what they did in anesthesia, which is a lot like an exercise test. You're measuring people's breathing,

you're measuring their blood pressure, their heart rate, and you're giving them drugs that affect their autonomic nervous system, and I've certainly done a lot of that. So I saw it as the flip side of the same coin. It is strange how to have pursued division for over 40 years now. I remember having the same thoughts

when I did my anesthesia rotation. I can't even remember if anesthesia was a required rotation in med school. I don't think it was, but it was positioned as sort of a very good thing to do, and I agree with that. And I had a field of it, even though I think by that point, I knew I was going to go into surgery, but I absolutely loved it as a sort of physiology geek. Anesthesia and critical care care for that matter are both two remarkable specialties that are, you know, the tip of the spear of what physiology is.

When you think about exercise or people climbing mountains or adapting to some unusual environment, the brain step back there has to do all sorts of incredible things to maintain what we call homeostasis or the internal environment in a way that allows you to survive and thrive. In anesthesia and critical care, you turn those mechanisms off, and the physicians and the nurses really become the patients brains to them as they regulate the breathing of the patient, the blood pressure of the patient, the heart rate, and so forth. So again, it's the flip side of the same point. As soon as I saw what the anesthesiologist did,

at the Tucson V8, it just sort of clicked. So where did you go on to do your residency in anesthesia? So the Mayo Clinic, and so what happened is I got out of medical school in Spranglers, early summer of 87, and I moved here, I've been here ever since. So I'll 35 years in a couple of weeks. Where did you grow up?

Did you grow up in a warm climate? Growing two-sign. Obviously the Mayo Clinic's a great program, but presumably there are other great anesthesia programs that weren't in the middle of a place like Rochester, no offense to those from Rochester. So what drew you to Mayo? I'd read this paper, a review article about skeletal muscle blood flow, the regulation of skeletal muscle blood flow. There were a lot of new ideas in the middle of the 80s about the regulation of skeletal muscle blood flow. The regulation of skeletal muscle blood flow. There were a lot of new ideas in the middle eighties about the regulation of skeletal muscle blood flow. And the world's leading expert was a man named John Shepherd, who is a very senior member of the faculty here. And I

wrote him a letter, you know, was before emailing stuff. So he was friends with the head of the department of man named Alan Sessler and John took it over to him. I wanted to be able to both do my residency and spend time in the lab. And I was able to work with Dr. Shepard. And our department and our residency program were very research friendly. So that's really why I decided to come to Rochester. But I thought I'd stay three or four years and go back to Tucson.

So that obviously didn't happen. Let's talk about exercise. People who listen to this podcast know that I'm really passionate about this idea of longevity. We think about longevity through the lens of five sort of modifiable behaviors, exercise, sleep, nutrition, emotional health, and all the tools around distressed tolerance, and then exogenous molecules. Those are the five things that as far as I can tell, mostly you can manipulate and they

can both impact your lifespan and your health span. Four of those are kind of behavioral. The medications aren't really behavioral in the sense that compliance is relatively straightforward. The other one is really require a shift in behavior and in mindset. Maybe we all have our biases in our blind spots, but I just think exercise is in a league of its own in terms of its potential. Both on the lifespan axis, you know, its ability to extend life and reduce all-cause mortality is well documented. We'll talk about that.

But also on the health span side, it really has no rival. So it's for that reason, I think, that we spend a lot of time inside our practice focusing on exercise. It is really the biggest pillar within what we do because it has the most impact. And unfortunately, or fortunately, it's also the most challenging one, I think, to get people to change their existing behaviors around because the time commitment is significant. So let's start with some of the basics,

just for folks who maybe aren't completely up to speed. What would you say if you're at a party and someone comes up to you and said, Mike, I understand you're really into this exercise thing. Can you explain to me why it is that exercise helps you live longer? I think there's a couple of things, Peter, and it's multifactorial. But the first thing is that the risk factors that contribute to cardiovascular disease, all osmortality, are all influenced by exercise and physical activity.

These would be blood pressure, diabetes, to some extent lipids and cholesterol, and also how you deal with stress. So I think you get the big three there. There are some other new age or second wave risk factors like indithereal function, the lining of the blood vessels in your body that improve with exercise. The way what's called your autonomic nervous system and people may have heard of vagal tone

or heart rate variability, that's also influenced positively by exercise. So I think there's five or six things, but what's interesting is when you add up each one, you know, the modest increase in cholesterol, modest reduction in blood pressure, those sorts of things, when you add them up, you get X, you know, percent improvement in health, span, life expectancy, any metric you want to use. But when you look at the epidemiology, people who do the sorts of things you just mentioned,

I have a much bigger benefit than just the simple sum of the other risk factors. So there does seem to be some sort of synergy here or some sort of X factor that we don't really understand yet. But again, this collection of lifestyle related factors, and again, the autonomic nervous system, blood pressure, lipids, the lining of the blood vessels, and diabetes would be the big five. I want to dive into a couple of these in-depth. You know, you've thought a lot and you've looked a lot at this literature,

and one can say, look, the epidemiology is so overwhelming, the hazard ratios are sort of absurd. When we're used to looking at a field like nutrition and looking at the hazard ratios in nutrition, they're very small. In fact, they're so small and also so inconsistent that it becomes almost impossible to assign a mortality benefit or addition to almost anything you can eat. I mean, literally jelly beans, tabacon, to kale. The hazard ratios are trivial and they flip flock from month to month. Yeah, let me tell you something it's really interesting. Good you brought this up. So I'm working on a review article on related topics and one of the things I'm looking at is all of what

you might describe as natural experiments where you have two groups of people that otherwise somewhere exposed to different things and that's a long long-used tool in epidemiology and people are now using economics and behavioral sciences and in fact these natural experiments the economist just got a Nobel Prize for a couple of years ago but the classic one is the London bus driver bus conductor story led by Jeremy Morris after World War II, where they showed the physically active conductors who were walking up and down the bus is all day, had much lower rates of cardiovascular disease and the sedentary bus drivers, and it was about

50 percent, and they had similar things with telephone operators versus people who were out walking around doing things. And you look at that 50% is incredibly consistent. Studies of Longshoreman, studies of Harvard alumni. There's one in the last 10 or 15 years of 50,000 male and 25,000 female finishers of the Vassa Lopez, 90 kilometer cross-country ski race in Sweden. And they compared them to match controls from the Swedish record system. And they showed, again, about a 50 percent reduction in cardiovascular

and all-cause mortality. There's data from the National Cancer Institute showing the same sorts of things and showing, you know, four, five or six, your increase in life expectancy, you know, among the people who got a substantial amount of physical activity or structured exercise, either one. The sort of take-home point for the listener is unlike nutritional epidemiology where the risk increases and risk reductions are very, very small and they're never consistent. I mean, there's some things that are consistent and consistently small. For example, vegetarians consistently have a small reduction in mortality, which of course then gets to the next point,

which is what are the confounders? And this is where I want to talk about it with exercise. And this is where the natural experiments are much better on the exercise front than they are on the nutrition front. You see, going back to the example you gave, which is a very famous one, guys running up and down the buses, they sort of conduct their guys versus the drivers,

that's a great natural experiment because it's really not amenable to a choice. You would be less likely to believe that the bus driver who sits there is also making poor choices relative to the other guy when he's not at work. In other words, we wouldn't really have a reason to believe that he's more likely to be a smoker, he's more likely to make poor food choices, etc.

Whereas when you look at the vegetarian to non-vegetarian dietary pattern in nutrition, it's pretty clear that a vegetarian diet is very restrictive diet, and therefore the person who's making that choice is likely very health conscious in a number of other ways, some of which are easy to... Yeah, they have a three to behaviors. Yeah, exactly. Some of which are easy to measure and correct for, like smoking, but many of which are not. That sort of makes the nutritional thing harder.

The exercise thing is pretty profound. So let's explain to people what it means when you have a hazard ratio of 0.5, which means a 50% reduction in all-cause mortality, what's the time frame that that's usually looking at and how does that translate to a five-year increase in life expectancy? The way you would say it is the relative risk of dying of heart disease in any given period of time, whether it's year or five years, ten years, whatever the study is doing is 50% lower. But, obviously, not everybody dies a cardioe of asker disease, people die of other things. And so then you have to translate that into sort of years of life gained.

And typically, the years of life gained are somewhere on the order, if you account for smoking of three to five years, something like that. And then if you look at the concept three to five years, something like that. And then if you look at the concept of health span, you may get six or eight years of improved health span. So, health span is you know Peter, how disability free you are. And so you have a four or five year increase in life expectancy and a four or five year additional increase in health span.

And the idea is to live a long time in the dive quickly with minimal disability. That's right. And I've always found that the current medical definition of health span, I understand why it exists because you have to be able to quantify things, but I've also found it to be not entirely helpful. Freedom from disease and disability, which is the current definition, I think that's a pretty low bar. One of the ways we try to get around this idea of the vagueness of freedom from disease and disability is to make it very, very granular.

And we do this by creating this model we have called the Centenary into Cathlon, which says, if you go out to your marginal decade and we define the marginal decade as the last decade of your life, so again, we don't know when that is, but let's just make them as easy and say, oh, that's going to be 79 to 89 or 81 to 91. You're in your marginal decade. What are the athletic events and the activities of daily living that you want to be able to do? But we do it by making people cross off things they do not want to do. So we make this a you have to opt out of things. And they're very specific. So it's like walking three miles in one hour, being able to climb X number of stairs, you know, 60 stairs that are eight inches in one minute, being able to carry 20 pounds

of groceries a certain distance, being able to get up off the floor at most one hand of support. So it's very specific stuff. And I think for most people, the initial reaction is, well, that's really easy. Like I can do most of these things today. But when you're a 45 year old reading that, I hope that's easy. I don't think they appreciate the precipitous decline that will occur without deliberate training. And it's for that reason that I think exercise has more potential to offset all of those things than anything else. Sleep, nutrition, certainly any medication.

To me, that's really what health span comes down to. It's not just I'm not disabled, but it's I'm really thriving. Yeah, I'm engaged. I can engage in what I want to engage in. I think Peter, you've hit the nail on the head. What we see in those decades, what's really instructive is if you look at the decline in performance in age group swimming, running, cycling, rowing, any sport where there's pretty good record keeping, is people can start to decline at age 30 without training. You can push that back to age 40 with training. In other words, if you work out every day in relatively art, but then something happens

to people in their middle 70s where there seems to be a steeper rise. And what's interesting about that steeper rise is it seems to shift from sort of a cardio pulmonary limitation to sort of a skeletal muscle strength slash frailty situation. And what you described in terms of getting up off the floor, 70% of 70 year olds can't get off the floor, not one hand, two hands, just can't get off the floor. And we both know from being doctors, if you look at what happens when a person in that age could fall, it's just no fun. So if you look at what really takes people out, it's things like falls, it's inability to do things. And so what happens is, you know, walking three miles in an hour takes some cardio pulmonary capability, but not a time, just some. Whereas being able to go up

the stairs takes more, being able to get off the floor, takes more. One of the things that people have to think about, especially as they get into their 40s and 50s, is adding strength or some sort of circuit training and agility training to their program. And one of the things I do is, I'm 63, almost 64, is I have the jump rope, my mother gave to me my 14, she gave me a beautiful boxer's jump rope,

leather with ball bearings and the works. I carry it with me when I travel because you can always jump rope even if it's out in the parking lot of a hotel. People think you're nuts, but it's a terrific exercise. It actually is for a number of reasons, including foot reactivity. The lack of foot reactivity is something that can contribute to the fall. So you're getting the cardio benefit, the coordination benefit, and also this gentle foot reactivity is something that can contribute to the fall. So you're getting the cardio benefit, the coordination benefit, and also this gentle foot

reactivity without, and it depends if you know how to skip like a box or you don't have to really pound your knees as well. And the other thing is you do that with somebody weight, things as simple as push ups or planks, and there's a place to do some pull ups. You're good to go. There's so many things you said there, Mike, that I want to go back on and just make sure people really capture because it's so important. We'll probably find the study and I'll link to it, but there's an amazing study that demonstrates like muscle mass changes,

strength changes and activity changes in men and women as they age. And it's one of those things where you don't actually need to understand the statistics to be able to see the figure. And it's exactly as you describe it at the age of 75, there is a cliff that is so violent. You can't believe what you're watching. It's at that cliff where physical activity level declines like this. It just goes, boom. Muscle mass goes, boom.

Strength, boom. Same thing. Of course, it begs the age-old question. Is the patient losing strength because they are no longer active, or are they no longer active because they have lost strength? My view is it's both. I think these things feed off each other. Which ones, the first insult I suspect, it's probably the loss of strength that contributes to the loss of activity, but then I think those feedback and accelerates this thing. Do you really get into a desk viral? That's why it becomes important to keep exercising relatively hard as you get over at least a few days a week to slow

this decline, you know, and there are remarkable examples. There are some Swedish cross-country skiers, men who were, you know, world and Olympic champions in the 40s and 50s. Many of them were woodsmen and lived in the countryside and made very active skiing and so forth. They were studied in their 80s. Now, you could argue that there was something special about these guys to begin with, or they would not have become champion athletes. But their rates of decline were quite modest, and more importantly, their fitness levels were similar to what you would see in people in very early middle age. The other interesting thing about that is the classic studies from the 1960s. These fighter pilots, Navy and Marine and Air Force fighter pilots were sitting in the

outer space. These were incredibly fit guys. They'd go for a week and come back completely out of the feed, couldn't stand up. Really in bad shape. And in 66 NASA commissioned folks at the University of Texas, Southwestern Medical Center in Dallas to put five college age males, two athletes at bed rest. And they had tremendous reductions in their fitness over just three weeks of bed rest. And interestingly, Ben Levine and his group in Dallas, along with the late Jerry Mitchell Mitchell brought these same men back 30 years later. So now there were early 50s and it's incredible but three weeks of bedrest you know caused losses of physiological function associated with 30 years of aging. Wow. So it's an incredible study and that's one of the things that is

instructive. Those sorts of small studies and that's why it's so important to just avoid in activity of any type and whether it's low grade physical activity, whether it's walking the dog, whether it's gardening, whether it's taking out flight of stairs once in a while or intentional working out. It's really the way to go. And as you point out really in those lifestyle factors you mentioned really sort of overwhelmed things, overwhelmed almost everything else. You mentioned and alluded to the danger of a fall

in later life, and this is something we've been doing a lot of research on internally, given our concern around bone mineral density in the aging population. The mortality when you look at 65 year olds and up who suffer a fall that results in the fracture of any part of the hip or femur at one year, depending on the study, it can be as low as 25%

as high as 60%. Yeah, the magic number is usually around 40, 50. Yeah, I want people to understand what we just said. You take all the 65 year olds and you look at those who fall and the fall results in a broken hip or femur. And you ask the question, how many of those people will be alive in 12 months? The answer is half of them. And the other half, it's not like the other half for...

They're not back to themselves necessarily. No, exactly. You want to avoid a major health like that for sure. You know, on the other thing, Peter, there's a couple other things that have really hit me. As we've talked, one is this man named Malester Braslow, who was this very famous epidemiologist who died in his late 90s, was at UCLA for many years, and he studied people in Oakland. In the late 50s and early 60s, who it to 90 and the sorts of four or five things you talked about, he identified the people in Oakland who made it to 90 and they were non-smokers,

they were no beasts, they remained physically active, they ate modestly, they stayed engaged in life and there were just five or six things that they did. The same is true in the Honolulu heart project when they've looked at a huge number of Japanese American males, same exact stuff that you mentioned. They weren't as focused on the small molecules, but exactly what you've described. Then I think about natural experiments. At the Cooper Clinic, they've looked at people's fitness levels. Now, that's not exactly the same as physical activity, but in general, the fittest people

are also the most active. They divided people into three or four groups of fitness, and then had a look at a so-called healthy eating index where you're junk food, junky, and edgy, okay, or where you're really conscious of your diet. The healthy eating index in people that weren't particularly fit did have something to do with all cosmortality, but among the fittest people, there was very little impact of diet on the outcomes Which is sort of interesting and always brings me back to the famous quote in a book about distance running called once a runner Where somebody said if the furnace is hot enough you can burn anything even big max

Now you have to take that with a grain of salt, but it does kind of give you the take home message and but just about what a powerful thing Exercises It does kind of give you the take home message, but just about what a powerful thing exercise is. There's a very common mantra that says, oh, you can't outrun a bad diet. And I would argue, that's probably not true. I think you can outrun a bad diet, but it's pretty hard to do. And most people don't understand the amount of running that's needed to do it. There's this incredible study from the 50s. People who worked at a juke plant in. And they categorized people on incredibly physically

active, you know, doing manual labor, hacking away on jute to make, I think, linen or rope. They're going to make rope with this stuff. All the way to office workers. As you got more and more physically active, people got lighter. Or you got more inactive, they got heavier. But what was interesting is people that were in the middle wrong of occupational physical activity also had slightly lower

caloric consumption, we mean very trim. If people are physically active enough, if you read the old papers about what lumberjacks were eating when they were chopping wood all day long, I mean it's 5,000,000 calories a day. The old order homage to walk around and do manual labor all day long and don't have tractors and stuff like that, they eat an awfully lot and very few of them are obese. You can out run a bad diet or can out exercise a bad diet. In a modern high calorie low physical activity world, I think is the caveat that has to go to that one. And yet when you look at athletes that are

doing insane amounts of exercise, most of them have a hard time keeping on weight. Yeah, there's a terrific study about the Tour de France where they get done every day and they're just handing them food. And, you know, these people are eating at live except when they're on the bike and even when they are on the bike.

And they have a hard time, and they're eating 6,000 calories a day, they weigh about 150 pounds. And they have a hard time keeping their weight. They are catabolic throughout the tour. I mean, they had finished in pretty bad shape. Correct. They look like not deaf camp survivors, but people who certainly haven't had a lot to

eat for a few weeks. So let's go back to something you said at the outset, which was the impact of exercise on the autonomic nervous system. Explain to folks what the autonomic nervous system is, how it differs from the sympathetic nervous system, and why it plays such an important role in our health, and of course how exercise impacts it. When we think about the nervous system normally we think about our brain, our eyes, our ears, and our senses, and also our ability to grab things, move our muscles, that sort of thing, feel pain or feel he or cold or sense the environment. But your autonomic nervous system is what controls

your internal environment and it's called homeostasis. So, you know, we can increase our metabolism. 10 or 20 fold with exercise, our body temperature rises a degree or two. And so this happens due to the actions of the autonomic nervous system. Now, there are two branches of the autonomic nervous system. There's this sympathetic nerves and the parasympathetic nerves.

And these used to be kind of categorized as fight or flight. You would either activate, especially the sympathetic nerves if you needed to fight or fly, run away. And whereas the parasympathetic nerves were seen as what happened when you were asleep, when you're digesting your food, so on and so forth. But it turns out there's kind of more of a balance in the yin and yang between the two that happen all the time.

But the parasympathetic nerves, and the most notable one is the vagus, they control part of your heart rate, make your heart rate slower. They also tend to lower blood pressure, and they're critical to digest your food. That's one side. The other side is the autonomic nervous system. Nerves that increase your heart rate, stimulate your blood vessels to constrict, help your muscles contract harder, and also do things like make you sweat. And the key thing to remember is that they help you regulate the internal environment,

and that exercise really keeps these things tuned up. And by having your autonomic nervous system a bit better tuned up, it can do a better job regulating your internal environment. The classic example being your blood pressure. Now of course, what everybody knows, and we're gonna talk in a moment about VO2 max testing and how that's done,

because I wanna get into the weeds on that. But when we have our patients tested, we have a protocol, we look at their blood pressure before and then we look at their blood pressure throughout. And then we want to look where they are percentile wise at the max exertion, what's their blood pressure? And without exception, a person's blood pressure goes up when we do a VO2 max test. So you take somebody whose blood pressure is 115 over 75 at the outset, they'll easily be 160 over 95 or 100, and that's completely normal and healthy at a max. Even higher if you measure it while they're weightlifting. So explain to folks why it is that during exercise, nothing looks good, right? Blood

pressure is high, heart rates high, heart rate variability is low. What is it about the recovery phase from exercise that produces a net positive effect, even though in the moment exercise presumably is doing things that are not necessarily in our body's best interest in that moment? I would say they are in their best interest because what happens is the system shifts a little bit to kind of meet the demands of the skeletal muscle. You got to be able to contract the muscles to exercise. And again, that's sort of consistent with the fight or flight thing. If you're going to run away or be in a fight, you want to be able to contract your muscles. And so to do that, you need to send more blood flow

to those muscles. And one of the ways you do that is by increasing your blood pressure, more blood pressure equals more flow. And the other thing you got to do is increase the pumping function of your heart. At rest, people's heart is beating about five liters or a little over a gallon a minute. During moderate exercise, it can be 10 liters a minute, during heavy exercise, 15 or 20. And in lead athletes, we're very trained and trained in very large hearts it can be 30 or 40 liters a minute. So what happens is you're pumping all that blood out against these blood vessels and so your blood pressure rises. So it's a completely normal thing to generate that large cardiac output. Cardiac output is heart rate times stroke volume that's the amount with each squeeze of

the heart and so naturally you're going to win increased your heart rate. So that's what happens. But then when you stop, as you mentioned, heart rate falls, blood pressure falls, and things look probably better than they did it in somebody who is untrained and has an exercise. What do we know about the rate of recovery? There's something called heart rate recovery, HRR, that is a pretty interesting metric. Tell us what we know about HRR. So people do a maximum exercise test in their heart rates, you know, 150, 160, 180, whatever their age is, and 220 minus your age is an interesting number, but there's a lot of patient to patient

or person to person variability. So what happens is how fast is your heart rate go back down to some number, how fast does it get until it's under 100, how fast it goes back to baseline, whatever. So the faster it goes down, the faster it goes down, the better the action of your vagal nerve, the nerve that slows your heart rate. The vagus nerve is also responsible mostly for your heart rate variability. And this nerve also suppresses funny heart needs and is protective when it's in good shape against arrhythmias and ventricular

tachycardia, ventricular fibrillation, sudden, all of those things. And so heart rate recovery, heart rate variability, all of those things are indirect markers of what we call vagal tone or vagal activity. And that's a good thing. Now heart rate availability can be quite genetic, right Mike? The absolute number in milliseconds between any two individuals can be quite distinct. And it seems to be not nearly as modifiable as some other factors. Have you found that to be the case? Again, it depends on what sorts of training people have been doing, what they've been exposed to. But in general, most people can get a nice training-braided cardio, which again is vagal tone.

And most people, if they're trained, can go from slow heart recovery to faster heart recovery, and also have more heart rate variability. So I think we're worried about the differences in the initial baseline peer, while interesting and what they might be attributable to, is probably less important than the fact that they're modifiable, as you mentioned, you know, as they say at the top of the show. So let's talk about this VO2 max test, because we're going to talk about what it means and how predictive it might be of an individual's

mortality. So let's just start by explaining to people what you do when a person comes into the lab. So what you do is you get them on a bike or a treadmill, you put some EKG electrodes on them, and they either run on the treadmill or ride a bike, and they have a nose clip on if you're going to measure it directly, and either a face mask or a mouthpiece that they breathe. And that allows us to measure how much air they breathe in, how much air they breathe out. We know that the air has 21% oxygen coming in. If we measure

the amount of oxygen in the expired air, we can make an estimate of how much oxygen has been consumed. And so what happens is when people start to exercise, they go from using about start to exercise, they go from using about three and a half mls per kg per minute, or maybe 250 mls or 300 mls, so like 10 or 12 ounces of oxygen per minute. An unfit person in their 30s or 40s can typically increase that about 8 or 10 fold to say 30 or 35 or about 3 liters of minute. to say 30 or 35 or about three liters a minute. And with training, most people can increase things at least 20% and if you have some ability and or you train very hard, some people can almost double it.

So what happens is once your VO2 max goes up, again, just like physical activity, it's a measure of physical fitness and it's also linked to all cause mortality. So the fitter you are, the lower your chance of dying in the next year or two years, five years, 10 years. For many years, they thought the thing sort of plateaued at what they call about 10 or 12 meds.

So that mean you're resting metabolic rate. So you have to be able to get 10 meds and 10 meds is being able to run one mile in about 10 minutes, minutes roughly for the average person Inrefort and Detroit have shown that that continues to rise Even up to 15 16 mats so people that are quite fit Continued to gain benefit in terms of all cosm mortality. I mentioned the cross-country skiers earlier And while they didn't do VO2 max test in those people, the people who had completed the most races and done the races the fastest, so people

who had both been active for the long period of time, and probably were the fittest, also had lower all cost mortality. And I compared to sedentary periods, but compared to people who had done a few races a little bit slower. So yeah, peak fitness matters. There's a paper in JAMA that I think is by far the most compelling description of this phenomenon. A couple of things are noteworthy about it. I've talked about this on a previous AMA. I would consider it one of the 10 most influential papers that I have read in terms

of changing how I think about health span and lifespan. As you said, the relationship is monotonic and it does not plateau. That's an important thing to appreciate, which is this is a more is better phenomenon. And very few things in physiology are more is better. Usually physiology behaves in use and upside down use, or maybe jays and things like that, or plateaus, sigmoid curves. But this is not the case here. This study that we're talking about,

put people into the bottom 25th percentile, 25th to 50th percentile, 50th to 75th, and then the last group it basically divided into 75th to 97 and a half, and then they had that little sliver of people that they called Elite that were at the top two and a half percentile. And all cosmortality just went lower and lower and lower and lower. liver of people that they called elite that were at the top two and a half percentile. And all cosmortality just went lower and lower and lower and lower.

And if you looked at the hazard ratio the other way, because we often think about hazard ratios in risk reduction, but if you look about it in risk increase, when you compared the people in the top two and a half percent, the VO2 max to the bottom 25 percent, the hazard ratio moving in that direction was 5.04 if my memory serves me correctly. That means there's a five-fold increase in all-cause mortality between the fittest 2.5% and the least fit 25%. And even when you took something less extreme, I believe if you looked at the least fit 25% to the third quartile, so the 50th to the 75th percentile, the hazard ratio was still about, but just below three, I think it was 2.75 ish, which was kind of right on par with the increase in mortality that you would see

from having end-stage renal disease, which is, by the way, greater than the hazard ratio associated with smoking. Being unfit is an incredible risk factor. And people like Frank Booth have argued that it should be, for lack of a better word, the risk factor. And Joe Barnes, one of my fellows at the time, she's not the University of Wisconsin. A faculty member, she and I wrote an editorial for Mayo Clinic Proceedings, maybe five ten years ago, where we said, look, if people had,

you know, 12, 13, 14 met peak exercise capacity, other than doing cancer screening, you could probably just ignore everything else. I don't think anybody's ready to go there, the sorts of people who do health screening, and that sort of thing. But if you screened people for physical fitness, and again, just did the routine cancer screening and you can even argue that you could probably cut back on the routine cancer screening for most things except skin cancers because fit people tend to be outside a bit more. You can make that argument and you can make it with a straight face and the data is there to support it.

And I would belt and suspend or say but look I still do the cancer screening. I'd still consider aggressive lipid management and things like that, but you're absolutely right. I mean, there's really no intervention that we have that's going to rival it. I think you mentioned lipids. I think there's a couple of things you gotta remember one, especially for people who pick it up late in life, exercise is not a vaccine.

And one of the most incredible studies ever done, and again, we're talking about in-of-one the experiment of nature sorts of things. There's a man named Clarence Demari who went to Boston Marathon seven times. Born, I think, in 1888 or 1890. Also, one of Medellin, the 24 Olympics cut up bronze, Medellin and Marathon. He really is almost like master athlete number one. He kept training his whole life. He ended up dying, I think, of stomach cancer at about age 70, so he didn't live to be a gazillion. But remember, he was born in 1888 or 1890.

Paul Dudley, why the famous cardiologist, we know him from something called the Wolf Parkinson-White Syndrome, a weird, kind of funny art people get. He did not talk to him tomorrow, and he'd run really till very late in life. And he had some plaque or fatty builds up and calcium build up in his coronary arteries, but his coronary arteries were huge, were just massive.

And subsequent to that, a man named Bill Haskell at Stanford in the middle 90s, studied a bunch of people who had done ultra-marathons and they did the same thing, except this time they put catheters in and injected drugs to make blood vessels expand and they showed the blood vessels, except this time they put catheters in and injected drugs to make the blood vessels expand. And they showed the blood vessels were bigger and they expanded more. So again, while you can still have some blockages, even if you exercise, and there are people with horrible lipids, who do in fact get heart disease in spite of exercise.

So it's not a complete vaccine. vaccine is overall protective effect is quite large, both in terms of what it does to people's lipids, but the fact that the blood vessels get so much bigger and the linings of the blood vessels are healthier. Mike, one of the things that we've looked at a lot internally is the literature that argues a different point, the literature that argues that in fact there's a J curve here. And we all agree that a person who doesn't do anything is at the highest risk. The literature is so unambiguous there,

it doesn't warrant any further discussion. But let's now look at the addition of work. Now, I just wanna make sure the listener understands the way we're gonna talk about this. Let's talk about these in Met Hours per week. A weird metric for sure. I've actually had to convert my own training into a met hour per week spreadsheet so that I can interpret what I do in the context of all the literature.

Totally weird, but let's explain to people what is right. So you can told us what a met is. One met is the metabolic expenditure of sitting at rest, which corresponds to about 3.5 milliliters per minute per kilogram of minute ventilation or actually VO2, so oxygen ventilation, not pulled-minute ventilation. Then let's talk about how that ramps up. How many mets is it, Mike, to walk three miles in an hour? Probably four, five, six, something like that, I don't know. Oh, is it that high?

Okay, I would have guessed lower. It may be because remember a 10-minute mile is 10 mets. 10-minute mile is six miles in an hour, and that's pretty non-linear. Yeah, you're right. It's probably about three to four mats, I would guess. And then of course, as you noted, to run six miles in an hour would be 10 mats. So let's say you did that. You ran six miles in an hour for an energy expenditure of 10 mats. So that would be 10 mat hours. You did 10 mats times one hour. And if you did that four times a week, and that was the only thing you did, you'd be at

40 mt hours per week of activity. So I do this for my training. I spend how much time am I on the bike at this many watts, at this many watts, and in the weight room and carrying my Rucksack. And I'm sort of in the 100 mt hours per week category. So if you look at the literature, the epidemiology on this, it would say my mortality risk might be higher. That would be the headline than someone who's doing 40 met hours per week.

In other words, it's a J curve. So it sort of starts up here. Highest mortality at nothing. Mortality comes down sort of naiders, depending on the study, between 50 and 75 met hours per week. And then the mortality tends to climb. Now, I won't go into this in great detail other than, we've looked at every one of these papers,

and we find significant fault in each of them. What do you see? Not all of them say that in the sense that some. That's right, some of them don't. The big NCI study was 650,000 patients, or subjects didn't say that. And again, what I really like is that cross-country ski paper that I mentioned from Scandinavia. If somebody is going to ski 90 kilometers,

and if they're going to do it year after year and they're going to do it fast, they have to be training a lot. You're going to have to be training a lot. You're going to be training year-round. You almost are certainly getting all sorts of meta-hours and training pretty hard. Now, the one caveat in all this, and I agree with you completely, I don't think the evidence for a J curve is particularly good. The other thing is in many of these studies, the number of people that are way out there is very small, so even one death somebody gets hit by a car or something,

it can make a difference. That's certainly one of the problems with a study from Copenhagen as I recall, or Norway. One of the Scandinavian capitals. I really think that the dispositive study here is the real world data from the Vassalopet story. The one thing that does happen is people do have an apparent increase in risk of atrial fibrillation.

A couple of caveats that the first thing is they do not have any increased risk of fatally arrhythmias. Atrial fib is no fun, but it certainly can lead to medical problems, but not typically to kill you. The sorts of things that kill you about ventricular arrhythmias, these are not seen in 3D grader or stint in these people that are really heavy exercises for their entire life. So, then the question becomes, do these people actually have more H.O.F.

relation, or is it just that they're exercising and noticing it? And that's the controversy. I think you would probably have to say that people who train what you're talking about for their entire life have some increased risk of atrial fib compared to people that are just super healthy otherwise. Physically active at that 50 to 70 met hour per week thing you're talking about or level you're talking about. But your risk of atrial fibrillation is still probably lower than people who are sedentary

hypertensive, obese, diabetic, and so forth. And there are good treatments for atrial fibrillation and you continue to be protected against fatally arrhythmias. And what do you think about sort of myocardial fibrosis? There's been some talk about that. Do we see compelling evidence to suggest? Again, the data from Ben Lovane's Group down in Dallas where they've done a bunch of echoes and loaded the art and all kinds of things. And they show that fit young people have very

flexible, compliant heart muscles. And they show that that declines with age, but doesn't decline nearly so fast in people that are either habitual exercises or people who remain master athletes or mean highly competitive. So again, I think that you can talk yourself into these sorts of things through a case report here, a case report there, but when you look at the sort of data that came from Benz Lab and other things, you see that this sort of training keeps the ventricles compliant, flexible, and able to handle the increased demands and pumping demands of exercise. So I think the fibrosis argument's a little spurious. I think we've talked a little bit earlier about large coronary arteries and people that

are herbitially physically active. We've talked that those arteries vasodilate better. They probably are less likely to generate a clot. And then we've just simply sat in your protected against fatally arrhythmias, we've just simply said there may be a subtle increase risk in atrial fibrillation. But again, good treatments for atrial fib. So I think they're in good shape.

I think in that regard, doing as much as you do, Peter, and the other thing to remember is that it's not an absolute vaccine or an absolute, you work out an hour day, you're never gonna get have heart disease. but I think your risk can be dramatically reduced. The other thing I think that argues against a J curve is the VO2 max data that we just discussed, which is an enormous cohort, probably the largest cohort after the Copenhagen cohort

and far more balanced in terms of the number of people in each group. And has been repeated in other populations. So there you have to ask the question, how is it that people in the top 2.3% of the number of people in each group. And has been repeated in other populations. So there you have to ask the question, how is it that people in the top 2.3% of the population for VO2 max have the lowest mortality by a long shot if they're not training significantly? I know those numbers very well. I mean, we put all of our patients up against that template

and we show them where they are and where we want them to be. And we actually hold them to an even higher standard mic. We kind of want our patients to be at the elite level for a decade below where they are actually are age wise. And I'll tell you in a moment why we do that. I wanna see if you agree with my logic. I don't see how you're gonna get there

doing 40 met hours per week. You can't achieve a VO2 max of that level, just doing a little bit of maintenance stuff here and there. You have to be training. Yeah, you have to be training. You have to be doing some high intensity training. So I agree with you.

The other thing is if you look at some classic studies by people like Bob Hickson and more recently Whistlaf's group up in Norway, people who do some longer intervals three or four times a week, you can't get a lot of bang for their buck in terms of VO2 max. I want to come back to that, Mike, because I want to talk very specifically about the different modalities for training. Before I do, I want to see if you can check my logic on this. A big part of where we come up with the reason you want to have a high VO2 max when you're young is we want to be able to prepare for the inevitability of decline. So I want to start by just asking you, what is the most up-to-date understanding of how much peak VO2 declines and let's do it in a non-training individual and a training individual?

So in general, people think VO2 max declines about 10% per decade, starting in the fourth decade, so sometime in your 30s. You know, some people say nine, some people say 12, some people say, but roughly 10%. A lot of that is driven by age-related decline in heart rate, but in people that are not training, it's driven because their heart can't pump as much blood and their muscles can't use it. So among people who are training, you start at a higher level, and then if people continue to train, you probably don't see a big decline until your late 30s or early 40s and we see that among athletes because there are

world-class endurance athletes in the early 40s and then you can reduce the rate of decline by about half up to certainly up to your 70s probably. Now not everybody keeps training hard. If people stop training, their VO2 max falls precipitously. Dr. Dave Costell, one of the founders of exercise physiology in the United States, studied a lot of the lead athletes in the 60s and 70s. He brought them back to his lab when these guys in the 90s, 1990s when they were in their late 40s and 50s. And about a third of them had continued to train very hard and had minimal reductions in their VO2 max.

A third had become sort of joggers, had some reduction. And there was a third that had just stopped doing anything and they looked like regular sedentary people. So you do have to stay at it. A group of master athletes out in the LA area were studied. Same sorts of things. People declined and their VO2 max declined, but among the people who continued to train intensely, in the case of the men do some

strength training, their VO2 max declined at a much lower rate. So you have a situation where it's 10% if you do nothing, and if you really work at it and stay with it at a really high level, it's maybe five or six percent per decade, but most people who've been super competitive can't quite keep doing that their entire life. So they drop off a little bit. But even if they drop off 10% per decade, they started a much higher baseline.

If your baseline is 60 versus 35, and you lose 10% per decade, you're still gonna be way, way, way ahead. And at age 60 or 70, you're gonna have a VO2 max value higher than 30-year-old. The reason we push so hard, Mike, for our patients to have as high a VO2 max as possible when they're in their 40s and 50s is based on this inevitability of decline. And with the hopes that we're extending life by a decade so that, hey, even though

actuarially you might only be expected to live to 81, we're kind of hoping you're going to get to 91. And if you say you want to be active, then we have to reverse engineer what that means. So what do you think is the VO2 max above which you have absolutely no limitation on any normal person's activities. In other words, if you said to me, hey look, when I'm in my 80s, I wanna be able to do pretty much anything reasonable.

I don't have to run a five minute mile, but what I do wanna be able to do is I wanna go on a hard hike. And if that means I gotta climb a hundred feet in half a mile, so be it. That's a great question. It goes back to one of your earlier comments about your scale versus the traditional kind of anti-frailty scale.

And what do you want to not be able to do when you're 85 or whatever the magic number is? Now, Vio2 of 14, ML's Prokage Pre-Minute are 4 Mets. 4 Mets is required from an auction consumption perspective for people to do their activities of daily living, which means an occasional somewhat brisk walk for a few minutes and be able to kind of get around the house, go to the supermarket and be quote independent, whatever that means.

If you want to be able to run a mile and 10 minutes, that would be 35 VO2 max. Yeah, 35 or 10 minutes. So somewhere between those two are the magic number. So I would say that, you know, if somebody in their 80s had a max in their 20s or lower 30s, that'd be terrific. We have arrived at 30 to 31 as the magic number. That would be a rough guess. And what's interesting that you mentioned that number. That would be a rough guess. And what's interesting that you mentioned that is those Scandinavian elites, skiers, I mentioned, had values in the very high thirties or low forties. In their 80s. Any sort of biological gifts or genetic gifts that those men had and or fact that they started to train, you know, probably be very physically active as youngsters and we're maximally physically active from age 13, 14 to probably

30. What account for that? I think 30 be a terrific goal. But I think the other thing too is how many pushups do you want to be able to do and how many sorts of body weight type of things you want to be able to do? What sort of agility maneuvers do you want to be able to do? And I think you know, you have to factor in orthopedic problems and that sort of thing. But again, we have good treatment for those now. And orthopedic surgeons can fix a lot of things.

Otherwise, it would have made people difficult for them to walk and move around. Yeah, we think a lot about those things. And we think that strength and stability need to be trained in parallel and as hard as we're training from a cardio standpoint. But I do think this idea that if you're trying to reverse engineer ending your life with a VO2 max in the mid-20s to high-30s, the good news is you are never going to not be able to do something that you want to do. If you're in the airport and the escalator isn't working, you don't care. Yeah, right. And I think the thing you have to ask people, and this really resonates, is, do you want

to be able to play with your grandchildren? That's one question for people. The escalator question, that's a terrific question. I was just in the airport last week, escalator down, and it's a long one. It was one of those really long ones. You got your carry on bag, plus your backpack, and you got to get up the escalator. Now, I'm sure somewhere out there, there was an elevator, but the point is, do you want to be able to do this stuff?

And if you do, then you have to do the math. You have to work to agree. And what's interesting, you see a few people around here in rural Minnesota who grew up on less than fully mechanized farms and remained active milking cows and doing these sorts of things, doing a whole lot of chores. It's remarkable the muscle mass that some of these men and women have. Well, if you look at in Japan, for example, the hilliest parts of Japan and some of the hilliest parts of Italy and Greece are where the longevity is the highest. And people have argued it's because people have to walk up and down the hills and also they keep their balance, they keep their glutes shrink, they don't fall, that sort of thing

appear. And also that they're, you know, living a more rustic lifestyle is probably getting them some de facto string training on a daily basis. Let's talk a little bit about VO2 max again in terms of like what is actually driving it. So let's go through all the variables. You've got gas exchange in the lungs. In the lung, correct? Then you have pump efficiency.

Correct. We went through the mechanics of that again, but just so people understand what we talk about. You've got stroke volume, contractility, of course, after load and preload and all these things that determine basically the efficacy of the pump to move the medium to the capillary bed and then you have capillary exchange in the muscle bed. So broadly speaking, let's just say those are three variables, right? You've got the gas exchange at the source, you've got the pump, and then you've got the gas exchange at the destination.

I know that's overly simplistic. So let's just think you got aerated long, long to blood, blood from the heart to the tissues and oxygen from the blood to the tissues. There's four or five steps like that and you enumerated three big ones. So, in general, oxygen uptake is cardiac output, how much blood you're pumping per minute times arteriovenous oxygen difference, how much blood you're extracting or oxygen you're extracting out of the blood.

It turns out that if you look at all the studies and all the people fit unfit trained, untrained, in general, the biggest issue is how much blood can you pump. So what is that heart rate times stroke volume equation? Where does that leave us? Now, when you train, you get so you can extract more. And if you're at high altitude, or if you've got problems that your lungs maybe the lungs don't work as well.

But in general, I like to tell people you cannot extract what has not been delivered. So the key is delivery. And that's heart rate time stroke volume. And interestingly, Peter, as you, I'm sure you've seen. If some of your fittest people actually have slightly lower peak heart rates. And one of the reasons is, is because their stroke volume

is so high, one of the really interesting, again, experiment of nature patients, or subjects is a man called Eskelthe Ebbison, who won gold medals in five Olympics and rowing for Denmark. They have serial VO2 max date on them from the time he was 18 or 19 until his early 40s. And his VO2 max date around, you know, 5.6 liters per minute, which is quite high. Anyway, it's about 70 kilos. I believe he's a lightweight rower. But his peak heart rate dropped from about 190 to 150 over that period of time, which all that means is that he was able to pump the same amount of blood, but he had to do more with each beat.

That's an insane example, actually. So in other words, in the individual as they age, we think that the majority of the reduction in VO2 max is coming from cardiac output reduction. Right. And the majority is probably coming from a reduction in peak heart rate, which can be buffered to some extent if you have a nice compliant ventricle like we talked about. I'll tell you, I'm not quite yet 50 and I am just sad by the reduction in my peak heart rate. It is really breaking my heart. I mean, I

I was never really high anyway, and I don't worry about it, you know, but I'm 63 so I'm not worried about it. I just I worry about when I work load is. I remember thinking like there will never be a day when I can't get my heart rate above X. But actually, I'll tell you, for me, it fell quite precipitously in my 20s. So as a teenager, when I was training, obscenely hard, inappropriately hard, a heart rate of 200 was an everyday occurrence. There was never a day in high school that my heart rate didn't hit 200 to 205 beats per minute. But the time I was in medical school,

so 24, 25 years old, all of a sudden it dropped immediately to about 180. It became very difficult to get over 180, which by the way was far lower than the 220 minus your age prediction. I was in two famous studies as a subject. One is this lactate threshold study when I was 19. And then a few years later, I went and worked one summer at Washington University in St. Louis and I stopped training. I just finished my last year of track and field at the University of Arizona had run 10,000 meters

and 30, 48 didn't done well on the pack tents, which was a fast, well, I was good enough to get labbed by the world record holders is what I like to tell people. But anyways, what happened is my peak heart rate was like 185 or 188. I can't remember. And over the period of 12 weeks of detraining,

it went up to about 10 beats a minute, which would have been, you know, in the high 190s, which would have been, quote, 220 minus my age, it's the time. There are all sorts of examples. There's a bunch of data on elite athletes showing that some of them have P-Cartry similar to 220 minus or age, but many are lower than that. And they're like Eskold Ebbis and there's some people that have been world record older Olympic champions that had p-card rates in the 150s. If I hit 170 today, that's a good day,

which is about 220 minus my age. No, that doesn't surprise me. My guess is I'd be high-pressing it to 140. I was talking with Lance Armstrong on a head-on on the podcast, maybe about a less than a year ago, actually, and we were talking about back in the heyday of his tours, they weren't really looking at their power meters when they were competing. So they trained with the power meter when it was race day for the time trial. You just went off heart rate. And I was just blown away.

I mean, you got to think Lance was winning the tours between 28 and 35. He was still holding 200 beats per minute for the entire time trial. So imagine, 45 minutes at 200 beats per minute when you're 30 plus years old is kind of insane. The other example would be a man named Bob Schuyl who was an American who won the 5,000 in 1964, who did interval training all day and all night. It was incredible how he trained. And I think the data someplace was like 154, 156. Jim Ryan's big, great milder was not particularly high in his 20s.

Yeah, so just incredible stroke volume. Correct, correct, correct. Big, heart, big pumps. All right, so let's talk a little bit about the training. Let's start with something that we haven't talked about, which, you know, when you look at the best high output endurance athletes today, it's one thing to talk about their peak engine performance, but it's easy to overlook what they're doing at the low end. You know, if you go sun, Milan on the podcast twice and we've talked at length about

Ted Deep Pogaccio. And it's amazing to talk about how high his FTP is, his functional threshold power. We could talk about his VO2 max, but equally amazing to that is how much power he can put out while keeping lactate below two millimole. He's over four watts per kilo while keeping lactate below two millimole. Why that's amazing for someone who doesn't ride a bike is if you took an average fit person off the street and said, hold four watts per kilo, they could maybe do it for a minute. Most people couldn't do it for a minute. And this guy can do it for four hours. That low end aerobic efficiency, I always try to explain

to my patients, if your VO2 max represents the height or peak of your pyramid, the wider your base, the higher your peak. Do you agree with that sentiment? Well, I would simply say as we think about performance and you think about these elites, we think obviously about their VO2 max and you start thinking about, you know,

with a lactate threshold, which would be sort of the FTP and they're all sort of related anaerobic threshold. There's a lot of terminology here. You can get an argument with people about the details, but what fraction of your VO2 max can you perform at for, you know, minute-stowers? And typically, it's about 60% in untrained, young to middle-aged people.

Lower in people that are really untrained, just sort of sedentary. And people that are very fit, it can be 75, 80, 85, even 90% of VO2 max, and some older athletes close to 100. So that's exactly what you describe. Somebody like that probably has a peak work rate that they could sustain for 10 or 20 minutes of 6, 7 watts per kilo. So the fact that they can do 4 watts per kilo forever shouldn't surprise anybody. You look at somebody like Mr. Kip Joge, you know, who's running 440 miles at a pace that doesn't really probably cause much of an increase in his blood like the deaths of levels

at all. Did they ever reveal any of those metrics when he... That date has been published now. Tell me, what was his lactate level at the completion of the just under two hour marathon? Remember, at the end of the race, you wouldn't have a lot of carbohydrate on board, but I would just simply say he can run 440 miles or over 12 miles an hour at levels that barely nudges lactic acid levels. When I first started thinking about this and making models of performance, I thought that the highest number was 85% of max, and it's probably closer to 90 for somebody like him. And when you were talking about FTP for one minute, the other interesting thing about that Peter is, you

know, the Kip Joggi challenge, people have put treadmills at 12 and a half miles an hour. Yep, I've seen it done. Yeah, and see how long somebody can last on the treadmill, you know, and it's like, yeah, they're getting spit off in 30 seconds. Yeah, less than that. It's insane. So same sort of thing, that sort of training. You know, for and these people are training two, three, four hours a day. If you look in terms of the runners, running is limited to some extent because of the impact just becomes a problem. You know, orthopedic issues, the impact, right? And so it's really difficult for people to run more than about 120 or 130 miles a week and ever run to hard training for a long periods of time. Now there are a few people

who can do it. And if you look at what Kipchogi does, it's almost identical. Even day for day, what Bill Rogers and Frank Shorter did. Does it at altitude? But there's a lot of medium, eight and 10 and 12 miles a run, a couple of hard interval sessions per week and long run. And that gets from 120 miles a run, a couple of hard interval sessions for a week and long run. And that gets them to 120 miles a week, weekend and a week out. Now the cyclists can do more. They don't have the impact.

Because you don't have that issue, but remember that with cycling, you're going up and you're going down and you have always a chance to take a break here and there, the swimmers do it, as well. And again, because swimming is very forgiving in terms of not beating people up, provided your shoulders, don't get a much tendonitis. But what's amazing is, is that if you look at

what the elite of the elite are doing, does not really change that much for 50 or 60 years. You have better equipment, you have better race, you got better this, better that. But in terms of if you look at the data on the elite of the elite from the late 60s and early 70s, it's not like Kipchog's VO2 Max was 90. It was high 70s, just as what you would anticipate and so forth. I think a lot of what's happened in terms of at the very edge of things has been better races, people that have longer careers, they don't stop when they're 25 or 26. Sports medicine is better so have longer careers, they don't stop when they're 25 or 26. Sports medicine is better so they get injured they can recover. We saw this last night

with Clay Thompson. He had two injuries that 30, 40 years ago would have been basically career in Indian. And he's come back from a combination of an ACL issue and Achilles especially used to just destroy people. He's playing very well. So I think those sorts of things that races are much better, you know, and they used to run the Boston marathon at noon whenever so often you'd get a, you know, a really hot day. So most of the improved performance can be equipment, these sort of social factors. Unfortunately, in the case of Mr. Armstrong, people, you know, bending the rules and so forth and so on. So let's talk about kind of the intensity levels that one needs to be training at.

I mean, we could pick the most extreme example and talk about Kipchogi. How many hours per week is Kipchogi running? Because I know he also does a ton of other strength training and body weight training. My guess is that the total amount of time he's running is somewhere between 14 and 18 or 20 hours a week. Yeah, he's covering a much greater ground, of course. You know, if you looked at it in terms of the lactate threshold or the equivalent of critical power on the bike, probably 60, 70 percent of that is fast, but not that fast.

They typically start off their group run sort of jogging and then they pick it up over time. Also remember that he's doing this at, know seven eight thousand feet. And then my understanding and reading his training program is a couple days a week he goes to a track and they run multiple 400 meters with say 200 meter jog or multiple kilometers with a 200 or 400 meter jog like 10 times a kilometer very fast. So the total amount of time he's running faster than race pace might just be 10 miles per week. So he's probably running about 60 or 70% of his stuff. Some of it quite slow, but most of it, you know,

medium fast, but certainly not where he's, can't talk to you where he's short or breath. Then he's probably spending about 20% of his time. He can still talk to you, but he's pushing it a little bit and probably 10% of his time where he's pushing it a lot. I mean, that's exactly my impression, and it's the same impression I have of elite cyclists and elite swimmers.

Those sorts of breakdowns, kind of the 60, 70, 20, 30, 10 are pretty typical. Now, what's interesting is that's really emerged the last say 20 years. If you look at people who've looked at the history of training and they have gotten training logs from people and I told you we have lab data on people that's quite good starting in the 19,

some even in the 1930s, but certainly by the 50s and 60s, we got plenty of good data. And if you look at what these individuals who have tremendous treadmill values, tremendous VO2 max values, ran very fast times on like dirt tracks and muddy conditions, that sort of thing. What we describe is a kind of a clergy bike now, certainly in the Aero bars.

Look at the swimsuits people raise. And so if you look at what those people were doing, they were doing all kinds of things. Runners in the 60s, there were people like Bob Schuul, a fascinating man who's still alive. His morning workout would be 40 times 100 meters with a short jogging between and his afternoon might workout might be 20 times 400 meters. And he rarely ran continuously at all except in races. And it would be a fast interval slow. And there are other people who ran up to 200 miles a week and hardly ever ran fast again

except in races and some strides. There are already people doing the sort of mixed training I described a minute ago. So what is interesting is the extent to which things have sort of converged on this 60, 70, 20, 30, 10 sort of model. It makes sense if you've ever done it yourself, and I can understand why there is a benefit to just the mitochondrial efficiency that comes from the continuous effort that you'd miss out on if you were just doing the short bursts. And similarly, yeah, right. You'd make more my take sure. Yeah. Well, that depends what short is. I mean, again, if you're moving to 400s and to

800s, unless you do a whole lot of them and the recovery is a jog because these guys aren't walking. Do you think there is a training benefit? I know there's a health benefit, but a training benefit in the lowest, so we kind of think about zone two as where Kipchogi is probably spending 60 to 70% of his time. He can still talk, and then obviously he's in zone three, four kind of race pace, and then he's like four, five, 10% of his mileage,

which is, you know, really stretching himself. Now, is Kipchogi or other athletes deliberately putting time into zone one, which is truly a recovery pace or? Yeah, they do that when they're recovering between intervals. And you would be amazed at how, because I did it many, many years ago. So the first mile or two can be very slow. It can be just almost a walk jog and then they kind of drift into it. But thinking about the listeners who are just trying to improve their health, that's

where you come back to physical activity versus intentional training. You start looking at the health benefits of just less than brisk walking. You know, purposeful but not really brisk walking, they're substantial. You know, parking your car farther out in the parking lot and strolling in, I think walking the dog, and that can mean all sorts of things, depending on what kind of talk you have. And who's in the neighborhood, the data on gardening. You could be out there,

hacking away weed with a machete, or most of us think about gardening as relatively light exercise. The health benefits of light physical activity, light exercise are substantial. And of light physical activity, light exercise are substantial. And remember, you're correct in the sense that at least from our perspective, there is no j curve and things go up, but it's not completely linear. The biggest benefit people get health-wise is the first 10 or 15 minutes a day. And why do you think that is? If you look at

what 10 or 15 minutes does, I mean, I think it begins to do things in your scalable most that improve your insulin sensitivity and help you fight against diabetes. I think just a tiny bit of additional physical activities, at least some buffer against weight gain. I think that there's some improvement in your, aligned in your blood vessels and probably some improvement in your autonomic function. Is your heart going to get bigger? You're going to get a more efficient cardiac pump, probably not.

But you're going to begin to do some of the things and the answers yes. So Mike, should those of us who really kind of care about this and care about using as many metrics as we can to understand this, should we be looking at heart rate recovery and adding that to our kind of repertoire of something we track in ourselves as we train? I think that there are people that are really into tech and monitoring and then they're sort of tech nudies. I'm a tech nudie and part of the reason is there wasn't as much around them when I started. I mean we just were getting digital watches and they weren't even stopwatches.

And the other reason is at the time one of the big innovations was rating of perceived exertion. You know the 6 to 20 scale or some people use a 1 to 10 scale about how hard you're working. And I think that what's been shown is because you know you can have a good day and a bad day in terms of the metrics that they're all sort of parallel. And if you learn to read your own body via you know the rating of perceived exertion and or metrics, you know find one you like and then just focus on sort of big picture things. So I would not get to hung up on heart rate recovery and to hung up on heart rate variability. I would just more say, how much are you doing?

30, 40, 60, 180 minutes a week. Are you also doing other forms or not a week a day? Are you also doing other forms of activity, you know, like taking the stairs, as you mentioned. And what sort of combination are you doing? How much of time are you spending? Where you're really short of breath, how much time are you spending? Where you're a little bit short of breath, and how much time is it kind of a pleasant sort of pace? I think that that sort of information can get you as much as you need. And I think the main thing then Peter is to make sure that you have some accountability,

whether it's a training partner, maybe with a device or a diary, maybe, you know, with just how far that run today, that sort of thing. So what is your current exercise regimen? I mean, you sort of downplayed it a minute, but 30 minutes and 40 seconds for a 10k. I don't think people understand how fast that is. I once ran a 225 marathon, but the older I get, the better it was, right? I'm a big believer in what's called hard easy.

Hard day, easy day. What I'll do, like tomorrow, be a hard day. So I'll get a stationary bike in my workout room on the bike and the rowing machine, do some sort of warm up for 10 to 15 minutes. Then I will do a circuit that starts with 25 squat thrust, a minute of jumping rope, static wall sit to failure,

and then some drop sets where you go down the weights deck. Then drop sets with incline flies, then drop sets with leg extensions, then drop sets with a combination of pull ups and lat pull downs and military press. Then some additional stuff for my legs, push ups, bar dips, and upright rows, followed by something else for my legs. So I alternate arms and legs, and I work my way through this with no rest. Drop sets on each thing for all large major muscle mass. And that takes about 22 minutes. 22 minutes for one circuit.

One circuit. Then I get on the bike and I'll do like eight times three minutes of a ladder where you start unloaded, go up a notch, go up a notch, go up a notch. And I get to maybe about 350 watts for the last 30 seconds. Come back down to about 100 watts, 350 watts. Do that times eight. And sorry, how long do you take to ladder? Three minutes.

Three minutes. Some 100 watts for our 30 seconds, 150 for 30, 200 for 30, 250 for 30, 330 for 30, 350 for 30, come back down. Times eight. And that takes about an hour and that. And how long in between your three minutes sets? No, you just go up and come right back down your rest from the so the recovery is

Exactly that takes about an hour and that'll fix your wagon for a while That'll be your hard day tomorrow and then what that'll be my hard day and I'll do that basically every other day or every third day My easy days will be something like this morning want to go to go do 20 more minutes, not because I need to do 20 minutes, because I wanted to watch the first bit of Obi-Wan Kenobi. So on my easy days are built around what documentary, or how many times can you watch the Mandalorian, how many Clint Eastwood movies can you watch? And this started during lockdown, right?

So my easy days are 30 to 40 minutes of light cycling transitioning to rowing back and forth days are 30 to 40 minutes of light cycling, transitioning to rowing back and forth of around 30 to 40 minutes. Sometimes I do one, sometimes if I come home from work, I do another one. But the goal there is an old concept called active rest. So I'm not trying to get a real training effect. I'm trying to loosen up from the day before it's worked, because I'm sore. You do what I describe. You warm up for 10 or 15 minutes, do 20 minutes of dropset and that type of intervals at the end. You will be sore, right? So you have to recover the next day. Now I'll do this for about six months and then probably

when it gets starts getting dark again. I'll do what I did like last year where I start just doing kind of maintenance circuits in terms of the strength. It may be only twice a week. And I'll start doing longer rides. We have a Peloton. I don't do any of the classes, but I started doing this hour of truth to see how many watts I could average for an hour. Okay, what are you at?

I think my best during lockdown last year was 316, average during the 16 watts for an hour. Wow, that's obscenely. Yeah, that's pretty good for you. And the things are calibrated pretty well. I got a lot of equipment. I got a white bike and I think they're pretty close. If you look online, they claim they're close, right? It's consistent with what I think. I haven't measured my VO2 max in a while. So I want to see if I get like 320 watts next year. What

do you think your VO2 max is right now? Well, I'll tell you back when I was quite young, it was 5.4 liters a minute. That what weight? My weight then was probably between 75, but close to 80 kilos. So I was right at under 70. And I think my weight now is probably about 95 kilos because I've actually made an effort to gain some weight. And I think my max is probably 4.5 liters a minute to be my guess. That's still an amazing wattage under any circumstance. Assuming the machine is okay, but I think it is because remember what I'm doing those ladders that I was telling you about are those pyramids. That's after I've done a heavy leg workout, you know, so my legs are pretty fatigued and I've done that. But remember I have some ability too because... Well clearly given what you ran, yeah.

I didn't really start running until my senior high school, so I started late. And I'm 6'4", and I like to tell people if I come back at a next life, I'll be really start running until my senior high school. So I started late and I'm 64 and I like to tell people If I come back at a next life, I'll be a swimmer or a roar because I used to show up with these tiny people I'm the world's largest relatively good distance runner formerly relatively good on your easy recovery day, Mike Are you just paying attention to RPE or are you looking at a split time on the rowing machine or as a low wattage bar on the bike? you looking at a split time on the rowing machine or as a low wattage bar on the bike. No, no, it's just all RPE.

It's really just active rest, which is a lost concept. Do you have a sense of what your heart rate is as a percentage of your max heart rate? No, I don't even measure it. It's probably about 140 is my peak heart rate. That would be my guess. Again, I go with RPE, I go to like suffer. It's unusual to be able to do intervals on your own

and really push it. Not everybody can do it. And that's why you need a class or you need a coach, or you need a group and so forth. But I'm lucky enough to be able to do it. So my training is really polarized. I mean, like really polarized. So let's talk about folks who are listening to this,

who want to boost their VO2 max. Let's talk about the different protocols that exist. I'll tell you what we typically tell patients to do, which is, in my experience, one of the most efficient ways that you can do it, but I'm curious as to what other ways. So we typically talk about a four by four, four on four off protocol. So we'll tell people, and again, the easiest way that I personally can do this is on a bike on an incline. And it can't be a very steep incline. It's got to be like 6% grade. I want to stay in the saddle, but I never want the resistance to go away. And I basically want to be in the saddle climbing

against resistance for four minutes. And I use a power meter and a heart rate. So I just want to keep the power as steady as I can. Inveriably, it dips in about the third minute, and then I can recover it in the fourth minute, psychologically. And then the recovery is four minutes of literally doing nothing, but rolling back to the starting line. And then it's basically just repeat that. No, no, I'm with you. What I tell people, for example, that if I come and say I want to run a faster marathon, I want to do this. I want to do that. You know, and they're running a lot of miles.

They need to get their V2 max up. And I tell them exactly what you've described. Sometimes I tell them five minutes and three minutes rest, sometimes whatever. People that are fitters, sometimes only two, like I would only take two minutes of rest. But four times four is terrific. So you would do something if you were thinking about running. I would tell people to do something that would be right at their sort of 5K race pace. Maybe a little faster or you would do the first one a little slower than your 5K race pace. The next one, you know, a little faster than

that, the next one a little faster, the next one faster than your 5K race pace. And depending on how fast you're running, if you're going pretty fast, then you would just jog in between. And if you were not going so fast, you'd walk in between. So that would be the sort of thing that I would describe to people. The classic training among elite runners is mile repeats, you know, four or five times one mile and then they jog a quarter mile or a half mile in between. And I personally have seen really good runners do you know 434 25 420 415 410 405 but I mean these were people getting ready for the Olympics. But sort of for the average person the hard part that I think requires a little bit of coaching

up front is you know you and I have done this our whole lives, so we sort of know what four minutes all out feels like. At 30 seconds in, you shouldn't be hurting too much. If you are, you've gone out too hard. It takes a little bit of work to coach somebody to understand what you're going for is a constant four minutes, but the suffering is disproportionately in the last 90 seconds. When you get done with the last one, the fourth one,

you do not want to be bending over. If you've go on a little bit of faster, you want to be bending over. So I call it the no-bendover rule. And then what people have to recognize, both for the four times four minutes and within the four minutes, is a good interval workout, and this sounds completely masochistic, is like putting your hand in warm water, and then slowly increasing the temperature in the water to where you can barely stand it anymore and then leave it in for a while. And then you turn it down, let your hand cool off and do it again. One of the things I think we've learned from the cyclist is a terrific phrase called manage your suffering. You know, you need to learn to manage your suffering.

And I think that's the other interesting thing about this type of training is to the extent, you know, people can have these sort of religious experiences to exercise these, this sort of interval training is one way to get them. Now, I completely agree. I mean, obviously we're cut from the same cloth in this way, but I think that there really is something wonderful

about experiencing your limits and understanding that level of discomfort. And if you're able to maintain your rhythm and tempo, Peter, why you do it? That's when you can have these sorts of experiences. I mean, one of the most beautiful things ever, and it wasn't a total endurance event. It was a little bit shorter, a couple of minutes. But to watch Michael Phelps win the butterfly and watch his stroke, He was good at everything but he was especially good at the butterfly. Most people's stroke has fallen apart and they end up taking more strokes the last 50 of a 200 meter butterfly. His stroke count, the second, third and fourth lap didn't change because he had that rhythm, that tempo.

And if you listen to the old school coaches, talk about interval training. They're constantly talking about tempo. What is your rhythm? What is your tempo? And why you're doing it? Why you're suffering, Peter? Why you're pushing it while it's hurting, while it's burning? The goal was to not lose your form and not lose your tempo.

I used to watch Michael Phelps train before he kind of broke out in the early 2000s. I lived in Baltimore because I did my residency at Hopkins and he used to train at a place called North Baltimore Aquatic. Now Michael, of course, within the swimming world was already an unbelievable prodigy because he had gone to the Olympics in Sydney, placed fifth. And each like 15 or something, which is quite young for a man. That's right. He became

the youngest male to ever set a world record in a time sport in early 01. He was still 15 when he yeah set the record for the 200 fly. So watching this 16 year old swimming at North Baltimore Aquatic Mbac, which his signature event of course was the 200 fly. Now it's 200 long course butterfly. I would put that up there with the 200 breast and the 400 IM as the three worst races in all of swimming. To me, it's like doing an 800-meter in the media hurdles on the track that the event doesn't exist. It's insane suffer. But here's the thing, Mike. His training, you never once saw him do a 200

fly. It was lots of 75s. Lots of 75s. And his coach, Bob Bowman, was really adamant about perfect form because if I recall, Michael had an unusual rhythm, which is that he breathed on every stroke. And when most people swear on butterfly, it was every other. You were head underwater for one stroke, head up for one down for one.

Michael, I'm pretty sure he would breathe every stroke, but as you pointed out, no one's form could rival his. And that's why he was usually the last guy to hit the wall at the 50, yet would come back and just devour everybody. And you see that with Edwin Moses, 13 steps between hurdles and the 400 hurdles in the late 70s with that innovation.

You see these people, you set with Keptogio, you're doing it for two hours, their ability to maintain this form and tempo. And as you watch it, as you watch it, Peter, you are awed by this sense of great effort and simultaneous relaxation. It's a real paradox. You see that in other sports,

do you see it when all of us get hot out? Are they hit the ball? Both violent and relaxed at the same time. You sit there and watch Steph Curry or Clay Thompson start launching balls and it's just incredible, the tempo, the rhythm, the form and the effort, but again, just how relaxed they are. It's just wild to think about even.

Now going back to our very, very recreational person who's never trained in their life. We don't use lactate testing on people at that level. We basically do the whole thing off RPE and we try to get 80% of their life, we don't use lactate testing on people at that level. We basically do the whole thing off RPE, and we try to get 80% of their time, which might start out at two to three hours per week, as we want you to be able to talk, but not enjoy it. I don't want you to be any higher than that. And then once we build up a bit of a reserve in that,

after maybe six months of that kind of training, we're sort of ready to move them to that next phase of, hey, once a week, I want months of that kind of training, we're sort of ready to move them to that next phase of, hey, once a week, I want you to do kind of four on four off for four rounds. Do you think that once a week doing four hard intervals is sufficient to boost VO2 max? It will increase it for sure in that vast majority of people, especially if they're doing the other stuff

you're talking about. What I really like about what you describe and what people don't realize, especially when you're going to have a relatively hard training for citizens, is that sometimes you have to train before you can really train. That's right. You got to train to train. Certainly, I've seen that in some studies, people that are really 60, 70 years old, is that they almost have to do three or four or six months of sort of pre-training before they are fit enough to train hard. So I think you're spot on there.

And my guess is after they've been able to do it for once a week for while you build them up to two times per week, I think the one thing that people need to recognize, and this comes from a man named Stan James, who I think is still practicing medicine. He's in his 90s. One of the pioneers of sports medicine orthopedic surgery, he's not operating anymore.

The last I checked, he was alive and well out in Eugene, Oregon. He worked with Coach Bill Bowerman, the great Oregon coach, one of the founders of Nike, the Waffle Shoegye. And they got into this hard easy thing, which is sort of what I do. And Dr. James would tell you that once people start doing more than about five or six hard sessions every two weeks, you're beginning to ask for some sort of load management issue, whether it's orthopedics,

whether it's just your fatigue, whether it's this, whether it's that. So I do think I can't remember the last day I didn't do anything. It's probably been years, but my guess is the number of times I do something hard is 120, 130 times per year. And my guess is I never go more than a week without doing something relatively intense. When you think about these sort of exceptional elite athletes, the kip chogies of the world, do you believe they have a finite number of exceptional performances in them? You know, people used to drift into the world rankings and they'd last, you know, maybe two Olympics, six, seven years. So they'd come in, kind of emerge right before one Olympiad, do well, do well in the next

one and kind of fade. But I think there's two things that have really changed. The first is that, again, sports medicine is better. So people do get injured, they can do things about it. And I think the second thing is just become so professionalized. People can, that are really, really good can now make enough money to make it worth their while to continue. You know, you see this in terms of the age of Olympians.

You know, it used to be very unusual to have women over age 20 in swimming. There was no college swimming, there was none of this, there was none of that. So there was a lot of teenagers. Now you see that drifting up, and you see people like Katie O'Decki having extended careers. It felt going 2000, 2004, 8, 12, and- 16. Going to five Olympics, yeah. That would have been inconceivable previously for swimmers.

You know, people hung around and maybe stayed for one additional Olympics and when they got done after college, sometimes too. But eventually they had to go get a job. But again, among the most elite who can now monetize is people can last longer. And you see it also in quote the major, unquote, professional sports.

You know, before the PD surgery was good and every knee surgery was an adventure, you know, somebody like Tom Brady. His career would have been over in 2009. And the other thing Peter is, if you're making $100,000 year, why keep playing? If you're making $23 million or whatever the number is,

you know, why not keep playing? And you look at in sports like running swimming cycling, you know, there's less of a kind of a journeyman group. But if you look at the NBA, the NFL, Major League Baseball, the salary scales are pretty good. And if people can play another couple of years, you know, this can be millions of dollars, millions of dollars for them. So they're very motivated to do this.

If you can be the eighth man on an NBA team and give people 15, 20 quality minutes of a game, you know, you're going to have a job for a long time. And again, if you're LeBron, you know, who apparently spend some huge amount of money on training and cook and all that other stuff. If you start thinking about spending X per year for a 40X paycheck, why not? Why stop? So, where do you think we are today, Mike, in performance enhancing drugs in sports? So cycling is probably the sport I would follow the closest of the major endurance sports. I guess I follow swimming as well, though not nearly as much as I did for 15 years prior. You know, I think when you go back and look at the cycling data, I love the way Lance talks about this, right?

You know, I think he's very open, right, to say, look, as long as there has been a tour de France, there has been a graying of the line, but there is a difference between the kind of high-octane cheating that was done in Lance's era, and sort of the low-octane cheating that was done in Lances era and sort of the low octane Cheating that was done in Eddie Merck's era when they were using a little bit of M. Fett. Here's what I would say about where we are with Dopey, so The testing has gotten better both in terms of the frequency of testing and the ability to detect you know the actual chemistry of the testing on the machines and the analytics ability to detect you know the actual chemistry of the testing of the machines at the analytics. If you look at the way what's called an abnormal test is called it's not like what we call

an abnormal test or an out of range test in clinical medicine. There are typically many standard deviations above average for these things and they're typically designed so there's not a lot of false positives. They don't have any false positives. So that gives people a room some room to microdose. And that's why you have relatively few positive tests. But occasionally there'll be people, you know, caught through investigations, judicial mechanisms, the police. And historically, many of the biggest bus have been the police. What I would simply

say is that the era of industrial strength dopey is over. People doing like the East Germans did and energy-inising females, so the extent that they really look like men. So I think that that is done. You say that even in light of what the Russians did is recently as less than a decade ago? I think what the Russians did was, again, relatively low dose by comparison. So I think there's plenty of room for microdosing, plenty of room for the kinds of manipulation, systemic manipulation, if there's a motivated government to do it. And there's plenty of room for other forms of corruption. But I do think that industrial strength, hoping has largely been, could stop permitted.

I think there are probably a bunch of novel compounds that are out there, you know, small peptides that cause this to be released or that to be released, which would be very, very difficult to detect. They'd have vanicely short half-lifes and so forth, and they would just boost your endogenous production of hormone X, Y, or Z, you know, something like a growth hormone releasing factor, you know, something that caused testosterone levels to go up or so forth. It's a cat and mouse game, I think for the kind of the big three amphetamines, EPO, slash blood doping and anabolic steroids, slash growth hormone, I think that testing has gotten better and industrial strength doping is over.

We don't know what we don't know about these novel compounds. And I think what we learned from the ballco situation is that there are all sorts of, you know, clever bathtub chemists who can make all sorts of things at home in the garage wherever it is in a very unregulated environment. And the barrier to entry for that kind of do it yourself sort of stuff is quite low. You can buy off course sorts of laboratory equipment and reagents and all sorts of things. So you don't have to be a big farm house to make interesting things. That's why I'd say we are with Doping. How familiar are you with Balco and the agents that were? Balco and Patrick Arnold.

You know Patrick? I don't know Patrick but I know who he is. The tragedy of Patrick Arnold, this tremendous guy with a master's degree, I believe in organic chemistry that he wasn't working for one of the big pharma companies making an anti-aging and I suck O'Peney a god bound. I've met Patrick a number of times, I've spent a lot of time speaking with him in a very unemotional way and just a very frank way he can explain in great detail exactly how he modified these androgens. in great detail exactly how he modified these androgens. The guy has, in sacripetic knowledge, apparently, of everything that's ever been synthesized in the androgens field, and what it does in terms of half-life and that metabolism and that sort of thing.

If you think about Victor Conte Jr., you know, a refugee from the Tower of Power. Junior College educated rock-slash-jazz musician, who is one of the great auto-didex ever out there. So I think with both of these individuals step back from the legal ethical ramifications and say what do they know and try to be a little bit objective about that. With Dopey you get into all sorts of other sort of areas. In the cultures those people were operating in, what was considered the cultural norm? Lance was not the only person doing industrial strength doping.

Was he doing it better than other people? If there were six ways to doping, person X was doing two and you were doing three, was Lance doing all six, that sort of thing. The other thing people have to recognize about doping in these incredibly competitive situations with these incredibly competitive situations with these incredibly competitive people, competitive organizations or people that have, you know,

foreign policy. Our country is better than yours because we want more metals. Is that there's always going to be some sort of arms race mentality. And you see it with training, you know, if you're in there lifting an hour day, I'm going to go lift an hour and 10 minutes a day. And so where does it stop? Do you still think that growth hormone, human growth hormone, which is of course not something that can readily be tested for, is still one of the more utilized agents, probably even today, for performance enhancement? There's probably some of it going on.

My guess is people are probably have drifted back to more short acting and origins, low dose short acting and origins. And hope for the best. That would be my guess. The same would be true with low-dose EPO, and or sort of related compounds or other factors. When you learn about growth harmonies typically, because Person X says that they're sending FedEx packages to athlete Y, you know, that kind of thing. So much of this has a judicial slash, you know, investigatory element to when you get to the big scandals.

Why do you think some sports seem more affected than others? So for example, swimming as a general rule seems less impacted than say cycling or even running, even though the demands are still pretty high. Hard to know. And how cultures head one way or the next, tribalistic behaviors, what's normal, what's not normal, and so forth, I think that that's key to understanding that sort of thing. We started this discussion, Mike, by talking about the miracles of exercise, right? We went through all of these things that exercise is doing physiologically and how the net impact of these things is so profound on the length of your life and the quality of your life.

There's no shortage of pharma companies out there that are trying to understand how can those benefits be put into a pill? Exercise pill, sure. Exactly. What is your level of optimism around the idea that some of the benefits of exercise could be basically captured by a pharmaceutical strategy? The efforts for exercise mimetic so far have been primarily things that increase mitochondrial biosynthesis.

And that appears like it at least works in animal models, and then you always how do you translate it from one to the next. But as I pointed out, exercise, sure, it makes your mitochondria better or makes more of them. But making your mitochondria better isn't going to make your autonomic nervous system better, isn't going to make your blood pressure better, isn't going to necessarily make the line in your blood vessels better, so on and so forth. So it's not going to make your heart bigger, so on and so forth. So I think at least so far, at least so far, these have been sort of one trick ponies. And while you might be able to get some benefits for people that are wheelchair bound or whatever,

quadriplegic, let's put it that way, not even wheelchair bound, can't exercise for some of the reasons that may be helpful. I think the jury is really still out. I'm not particularly enthusiastic about it. I don't think you're ever gonna get one that does any more than a little bit. I think more interestingly, I like to tell people, you know, at some level, there's already an exercise in Medi-Cout there.

It's called the polypil. If you look at the data on people who get a combination, one pill a day of low-dose statins, low-dose blood pressure meds, and maybe one or two other components, it causes pretty nice reductions in risk factors in most people. Because doses are low, the side effects tend to be low, and so forth. But again, none of this is patentable, but if people don't want to exercise, can exercise, you know, a better choice

than trying to find some mythical exercise when a medic is to use a polypill, which would do the same thing. She'd give them a stab in their cholesterol, goes down, man, maybe they're into theal function, gets better. You do a tiny bit of metformin, maybe their glucose tolerance gets better.

You do a bit of beta blockers, their heart rate is lower, that sort of thing. And again, I'm not advocating this, but there's all sorts of data out there that a polypill, data and speculation and modeling suggesting a polypill is a quote legitimate, unquote, whatever that means. Potential public health strategy

for lifestyle diseases. I would encourage people to exercise and do the sorts of things you're talking about, but I think Polly Pills have been understudied. Like, what is it you're most excited about right now? What is the question you're most interested in trying to answer? I'm excited about a lot of things.

We've got some interesting data with Sarah Baker on sex differences in blood pressure regulation. I'm quite interested in human performance. As you know, Peter, the first thing they teach in medical school is that a right shift in the oxygen hemoglobin dissociation curve is good for you at altitude. Well, all animals that are genetically adapted over centuries, millennia, to high altitude and llamas, the birds at Flavre Mountain ever since so far, they're left shifted. We've been doing some really cool, hypoxia studies and people with rare

left shifted hemoglobin. I'm super interested in that just as sort of a physiological question. Can you explain to folks what the right and left shift looks like on the hemoglobin dissociation curve? Think of a curvilinear situation or an S-shaped curve, an italicized curve. And so the idea is that if you shift it to the right, the red stuff, the hemoglobin in your blood, doesn't hold onto the oxygen, so it releases it and can give the oxygen to the tissue, and that's great if it's

hypoxic. Now the problem with that is it's harder for that kind of hemoglobin to get the oxygen out of the lung. And animals like llamas, and like these incredible athletes called the bar-headed goose that fly over Mount Everest without acclamation they're living in the plains of Mongolia. One day, they just fly over Mount Everest and go to India. They're left shifted because they prefer to make sure that they can pick up the auction out of the year in their lungs at very high altitude. So we have a family of people and some other subjects that we studied that are left shifted in. Sorry, meaning there is a family of people who genetically shift left instead of shift right

under hypoxic conditions. And there's all sorts of hemoglobin variants. They're not like sickle cell or anything like that. Very interesting, Peter, to be sitting in the lab having somebody breathe in 10 percent action talking to you. These left shifted people do that. It's crazy. It's just wild. What is the FIO2 at the top of Everest, by the way, just for comparison?

Barometric pressure is about 250. So I'd be 21% of 250. So we're roughly about 50. So once you get it into your lung, I think arterial is about in the 30s. Yeah, at 15%, which is 3,000 meters, these people exercise like, you know, they do fine. So I'm very interested in that. And then as I mentioned, you know, before we went on, is through a weird collection of events. When the pandemic struck in March and early April of 2020, I somehow became the principal investigator of the U.S. Convalescent Plasma Program, a program that was initially designed to facilitate 5,000 patients, compassion and use of convalescent plasma, antibody-rich plasma from recovered COVID patients that we

would give to people who had disease and hopefully the antibodies would help them. Through all sorts of twists and turns, we ended up doing over 100,000 people. We found evidence if we gave people a whole lot of antibody early in the course of disease, we made them better. We also found some evidence that it was probably very helpful in people that were immune suppressed. And that has been the gift that keeps giving.

So at age 60, you know, 162, 63, I kept kind of a new career in immunology and infectious disease. And so we're pursuing that. And we're especially interested in that Peter because whenever COVID sort of finally winds down about 2 to 3% of the population is what we call B cell deficient. So B cells are the cells in your body that make antibodies help you respond to fight the virus or respond to the vaccine. About 2 or 3% of the people don't have any or don't have very many and those people

continue will continue to get COVID and other forms of infectious disease. And antibody therapies essential to help those folks. You know, I'm very happy that we've published papers and high profile journals, but we just learned yesterday from people magazine of all places that the actor Jeff Bridges. The dude himself. The dude from the Big Lebowski. The dude himself had gotten lymphoma, gotten drugs that depleted his B cells, which is typical for lymphoma patients. God COVID, he could not clear the COVID and responded to convalescent plasma. What's the total volume of plasma you need to give a patient in that setting? If you get really high-tider stuff to 400 ml, that's it. One-time treatment?

Yeah, typically. Sometimes we give people more and what's been helpful for Peter is that we now have people that have been both vaccinated and they've had a breakthrough infection or they've had an infection and been vaccinated, right? So they have hybrid immunity. And those people make their plasma has a whole whole lot of antibodies in them and their broad spectrum. So they cover all the variants and they almost anticipate future variants because of the way the immune system works, is a sort of a sloppy replicator. And so they cover a lot of the variants, they cover potential future variants. And as monoclonal antibodies, which have been super helpful during the pandemic, as those get less effective due to escape variants, this very

high-tider plasma is still available. We're back doing exercise studies, we're back writing papers about exercise and doing our regular physiology. I think this antibody therapy is really took a bite out of me. It's like what Jim Bowton said, the great picture, you spend your life gripping the ball

and thinking about your grip on the ball in the reality. It was the other way around, the ball had a grip on you. So I've been thinking a lot about antibodies and maybe antibodies have been thinking about me because it's really hard to stop thinking about it because it's so interesting. And we get reports back to us from not famous patients

that are very similar to what we've heard in Mr. Bridges. So we're quite excited to pursue these solutions for our immune suppress patients. When I started medical school in 1982, those sorts of patients, their life expectancy was quite low. Now our patients with hemoligmency, multiple myeloma, lymphoma, leukemias,

a lot of those people live a long, long time. How long after a person is infected and recovered from infection? Are they a suitable plasma donor? Within about two to three weeks. When does that window close? It goes on for three or four months You know probably up to six months and it would probably reopen if they got boosted that sort of thing

You only get sufficient antibodies from people who have had the actual infection not from people who just go get a booster Initially because there were no vaccines. We only had people that had the normal infection since the vaccines It become widely available in the last you almost 18 almost 18 months now, or 15, 16 months, we've now been able to get people who've had both. The people that have had both are really super donors. And we can work with those people to come back in and get multiple units. We collect our own blood at May,

or we have a terrific blood bank here locally, but they're using it at Hopkins, they're using it at Harvard, using it at Einstein, a lot of the big places. We're working with the societies, the Food and Drug Administration, and others like the lymphoma, or leukemia lymphoma society, the CLL group, infectious disease, or excuse me, immune deficiency foundation, to make sure that we have this available for those

sorts of patients. They're doing this at scale in France to about 50 patients a week, which would be about 300 a week in the US, if you account for population differences. So that's one of the things we're quite interested in. This is something people can donate. It's a way for people to give back. Are you able to find sufficient donors? Are there enough donors that are aware? Again, because there's so many people who've been both infected and broken through. There's always logistical issues in terms of getting a person to the blood collecting center, getting it here, getting it there. But availability should be pretty high. And with plasma, do you still have to do a type in cross?

Got to still be typed in cross, and people are, they have to be eligible to do otherwise, don't need blood. But during the peak of plasma use prior to the vaccines and prior to the monopmonial, 2030, 40,000 units a week were being used in the country. And in the weeks, when more plasma was being used, the death rate two weeks later was lower. So there's a pretty nice correlation between it. But again, I think we've talked about training, we've talked a little bit about coaching,

we've talked about participation in support and so forth. But I think one of the things that really helped me work with the government and work with our team instead of do a 5,000 person demonstration project to a really a treatment registry in over 100,000 patients was the organizational skills I learned from my coaches. And I used to joke with higher ups and the food and drug administration. They'd say, well, how did you do that? I'd say, I'm a recovering physical educator. And that was always good for a laughter and at least a few dark hours.

Last question Mike, given your longstanding history and athletics both personally and professionally, are you optimistic or pessimistic about the future of Americans based on the level of physical activity that we see? We need to do something. We need to do something and I think it really reflects our society in general. I think that you have, for lack of a better word, upper middle class kids who have access to superb coaching, to superb facilities and to programmatic things. I think we've got a tremendous problem with play

and unstructured play, things that when I was growing up in the 60s and 70s that were done through the park district and the school district, I think a lot of those opportunities have fallen by the wayside. The kids who were college athletes used to come back and have open gym all over Tucson when I was a kid. There's no open gym at the high schools in Rochester, Minnesota, a rich community in the summer. And the advantage of open gym was, you got people off the street and they were doing things, and the police knew where we were. Which they're always very pleased about,

if they know that all the high energy boys are in one place, it makes their life a little easier as well. Yeah, I think it's a real problem. So I think we'll have these incredible performances by the kids who have access, but I think that what we're doing in the rest of the world is problematic. I guess if I could do anything,

I'd start a national open gym movement, winter, summer, whatever, because we have a lot of nice facilities that are used just limited number of time per day. Could you imagine if you were ZAR, and you could sort of do anything, and you just said, no matter what your lot is in life, if you're a school child,

if you're a person who works in an office, if you're a person who works in an office, if you're a person who works in, we somehow rearrange the day such that every person has a mandatory one-hour activity. You could make it exercise. You can go to the gym for an hour, but it could also be, look, at a minimum, you got to go out and walk. Well, you know, it's interesting. You mentioned that because in our department with remote work and so forth, this is broken hell a bit, but we had a number of secretaries. They were all women, the ladies women.

And we have this huge, deep bunker system with the bowels of the hospital with these huge hallways. And it's about a mile around the place. And these folks would go down and walk at lunch. They'd bring their tennis shoes to work. They would meet up with their pals and go do 30, 40 minutes a day of Laps at lunchtime with the Secretaries all over the hospital and it was, I think, terrific for them. I think it was a social event for them. And I think that they solved a lot of problems too and they actually made them way more productive.

As I said at the outset, I've enjoyed reading your papers for more than two decades and I'll continue to do so. And it's been great to chat and hopefully we can meet in person at some point and do work out together. Yeah, I look forward to it. Thank you for listening to this week's episode of The Drive. If you're interested in diving deeper into any topics we discuss, we've created a membership program that allows us to bring you more in-depth, exclusive content without relying on paid ads.

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