Peter Attia MD217 ‒ Exercise, VO2 max, and longevity | Mike Joyner, M.D.
EVERY SPOKEN WORD
135 min read · 26,797 words- 0:00 – 0:08
Intro
- PAPeter Attia
[upbeat music] Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Attia. [upbeat music]
- 0:08 – 5:25
Mike’s training as an anesthesiologist and interest in exercise physiology
- PAPeter Attia
It is such a pleasure to be, uh, at least virtually sitting here with you today. Um, as I was kind of alluding to a moment ago, you know, if 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, um, y- you know, you would be pretty far up there in terms of duration. So, you know, growing up, uh, you know, endurance sports were, were always sort of something that, 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, you know, kind of understanding physiology better. And so, you know, it's been 25 or 30 years that I've been reading your studies. Uh-
- MJMike Joyner
Huh
- PAPeter Attia
... so it's, in some ways it's a long time coming to, to finally be sitting down with you, and, uh, I h- hope to meet you in person one day.
- MJMike Joyner
Yeah, Peter, thanks much, and it's been, uh, great to be able a 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 [laughs] or 30 years, so it's, uh, very validating. Thank you.
- PAPeter Attia
S- so let- let's talk a little bit about your, your background. You're a physician by training. Uh, I, I believe you're an anesthesiologist, correct?
- MJMike Joyner
Correct.
- PAPeter Attia
Uh, so tell me a little bit about that. So wh- wh- you know, you decided in medical school you wanted to do anesthesia.
- MJMike Joyner
Right.
- PAPeter Attia
But I... Y- 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?
- MJMike Joyner
So Peter, before I went to medical school, I actually, uh, volunteered to be a subject in a study on the lactate threshold or anaerobic threshold when I was 19 at the University of Arizona, and luckily there were excellent 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, putting catheters in people, in humans, I... It might be wise to go to medical school. So this was always sort of my vision starting at, at about age 20 or 21. And then what happened is I was thinking of going to cardiology or pulmonary medicine, and I was working at the, at the U- Tucson 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 c- coin a- and so it just sort of happened, and, and, um, it is strange though to have, uh, pursued this vision for, you know, over 40 years now.
- PAPeter Attia
Yeah, I, 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, I, I agree with that. And I had a field day even though I think by that point I knew I was gonna go into-
- MJMike Joyner
Mm-hmm
- PAPeter Attia
... surgery, but I, I absolutely loved it. I, I, I think as a, as a sort of physiology geek-
- MJMike Joyner
Yep
- PAPeter Attia
... um, anesthesia and critical care for that matter are both-
- MJMike Joyner
Correct
- PAPeter Attia
... two remarkable specialties that are, um, you know, the, the, the, like, the, you know, the tip of the spear of what physiology is.
- MJMike Joyner
Well, well, you know, it's interesting too, Peter, because, uh, when you think about exercise or people climbing mountains or adapting to some unusual environment, you know, the, the, the brainstem 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. Well, in, in anesthesia and critical care, you turn those mechanisms off, and the physicians and the nurses really become the patient's brainstem as they regulate the breathing of the patient, the blood pressure of the patient, the heart rate and so forth. So, so again, it's the flip side of the same coin. And, and, uh, as soon as I saw what the anesthesiologist did at the Tucson VA, it, it just sort of clicked.
- PAPeter Attia
So where did you go on to do your residency in anesthesia?
- MJMike Joyner
So at the Mayo Clinic, and so what happened is I got out of medical school in, in, in the spring or s- early summer of '87, and I moved here. I've been here ever since. So 35 years in a couple of weeks.
- PAPeter Attia
And so y- you, uh, did... Where did you grow up? Did you grow up in a warm climate?
- MJMike Joyner
Grew up in Tucson.
- PAPeter Attia
So what... I mean, obviously the Mayo Clinic's a great program-
- MJMike Joyner
[laughs]
- PAPeter Attia
... but presumably there were other great anesthesia programs that weren't-
- MJMike Joyner
Right
- PAPeter Attia
... in the middle of a place like Rochester, no offense to those from Rochester.
- MJMike Joyner
Right.
- PAPeter Attia
So what, what drew, what drew you to Mayo?
- MJMike Joyner
Well, I, I'd read this paper, uh, a review article about skeletal muscle blood flow, the regulation of skeletal muscle blood flow, and there were a lot of new ideas in the middle '80s about the regulation of skeletal muscle blood flow, and the world's leading expert was a man named John Shepherd, who was a very senior member of the faculty here. And I wrote him a letter and, um, he, you know, it was before email and stuff, so he was friends with the, the head of the department, a man named Alan Sessler, and John took it over to him. And, uh, I wanted to be able to both do my residency and, and spend time in the lab, and I was able to work with Dr. Shepherd. And, and, uh, our department and our residency program were very, uh, research friendly. Uh, so that's really why I decided to come to Rochester, but I thought I, thought I'd stay, you know, three or four years and go back to Tucson, so that obviously didn't happen.
- 5:25 – 8:54
How exercise increases longevity
- PAPeter Attia
So, um, let's talk about exercise. You know, I-
- MJMike Joyner
Right
- PAPeter Attia
... people who listen to this podcast know that, um, I'm, I'm really passionate about this idea of longevity.
- MJMike Joyner
Right.
- PAPeter Attia
Think about longevity through the lens of five sort of modifiable behaviors.
- MJMike Joyner
Yep.
- PAPeter Attia
Exercise, sleep, nutrition, um, emotional health, and all the tools around distress tolerance, and then exogenous molecules. Those are the five things that as far as I can tell mostly you can manipulate.
- MJMike Joyner
Correct.
- PAPeter Attia
And they can b- both impact your lifespan and your healthspan. Um, th- four of those are kind of behavioral Right? All the-
- MJMike Joyner
Right
- PAPeter Attia
... the, the medications aren't really behavioral in the sense that, you know, compliance is relatively straightforward. The other ones really require a shift in, in, in behavior and in, and in mindset. And of these, I, I just, again, I, maybe we all have our biases and our blind spots, but I just think exercise is in a league of its own in terms of its potential. Uh, both on the lifespan axis, so it, you know, its ability to extend life and reduce all-cause mortality is well documented. We'll talk about that.
- MJMike Joyner
Right.
- PAPeter Attia
Uh, but also on the healthspan side, it really has no rival.
- MJMike Joyner
Yeah.
- PAPeter Attia
So it's for that reason I think that we spend a lot of time inside our practice focusing on exercise.
- MJMike Joyner
Right.
- PAPeter Attia
It, it is really the biggest pillar within what we do, uh, because it has the most impact, and unfortunately or fortunately, it's, it's also the most challenging one, I think, to, uh, to get people to change their, um, existing behaviors around because the time commitment is significant. [lips smack] So, uh, let's start with some of the basics, just for folks who-
- MJMike Joyner
Right
- PAPeter Attia
... maybe aren't completely up to speed. What, what would you say if you're at a party and somebody came up to you and said, "Mike, I, I understand you're really into this exercise thing. Can you, can you explain to me why it is that exercise helps you live longer?"
- MJMike Joyner
I, I think there's a, a couple things, Peter, and it's multifactorial. The, the, the first thing is that, you know, the risk factors that contribute to cardiovascular disease, all mor- cause mortality, are all influenced by exercise and physical activity. These would be blood pressure, diabetes, uh, 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 kind of, uh, new age or second, second wave risk factors like endothelial function, the lining of the blood vessels, uh, the, the, in your body that improve with exercise. The way... What's called your autonomic nervous system, and, and people may have heard of vagal tone or heart rate variability, uh, 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, a modest inc- increase in, uh, cholesterol, a modest reduction in blood pressure, those sorts of things. When you add 'em up, you get X, you know, percent improvement in, in health, uh, uh, span, life expectancy, any metric you wanna use. But when you look at the epidemiology, people who do the sorts of things you just mentioned, uh, have a, a much bigger benefit than just the, 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, uh, understand yet.
- PAPeter Attia
Yeah.
- MJMike Joyner
But again... Yeah. Go ahead.
- PAPeter Attia
N- no, no. You, you go ahead.
- MJMike Joyner
I was just gonna say this collection of lifestyle related factors, uh, which are, are, are really critical, and again, uh, the autonomic nervous system, blood pressure, uh, lipids, the lining of the blood vessels, and, and diabetes would be the big five.
- 8:54 – 14:33
The impressive data on the benefits of exercise
- PAPeter Attia
I wanna dive into a couple of these in, in depth.
- MJMike Joyner
Yeah.
- PAPeter Attia
Uh, one of the things I, I would say at the, uh, before we do so is, you know, you've thought a lot and you've looked a lot at this literature, and you-
- MJMike Joyner
Mm-hmm
- PAPeter Attia
... you know, one can, one can say, look, the epidemiology is so overwhelming-
- MJMike Joyner
Correct
- PAPeter Attia
... that, that it's... I mean, the hazard ratios are, are sort of absurd, right?
- MJMike Joyner
Yep.
- PAPeter Attia
When we, 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-
- MJMike Joyner
Correct
- PAPeter Attia
... small, um, and also so inconsistent that it becomes almost impossible to assign a mortality benefit or-
- MJMike Joyner
Correct
- PAPeter Attia
... addition to almost anything you can eat. I mean, literally. Jelly beans to bacon to kale. The hazard ratios are trivial, and they flip-flop from month to month.
- MJMike Joyner
Correct. Well, and, and, and yeah, let me tell you something that's really interesting. It's 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-
- PAPeter Attia
Yeah
- MJMike Joyner
... uh, where you have two groups of people that are otherwise similar exposed to different things, and that's a long, long, uh, long used tool in epidemiology and, and people are now using it in economics and behavioral sciences. And in fact, these natural experiments, uh, the economists just got a Nobel Prize for 'em a couple of years ago.
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
But the classic one is the, is the London bus driver, bus conductor story led by Jeremy Morris, uh, after World War II where they showed the physically active conductors who were walking up and down the, the buses all day had much lower rates of cardiovascular disease than the, the sedentary, uh-
- PAPeter Attia
Drivers
- MJMike Joyner
... bus drivers.
- PAPeter Attia
Yeah.
- MJMike Joyner
And it was about 50%. And they had similar things with telephone operators versus people who were out walking around doing things. And what's interesting is y- you look at that 50%, it's, it's incredibly consistent. Incredibly consistent. Those studies, studies of longshoremen, studies of Harvard alumni, uh, there's one in the last, uh, 10 or 15 years of, uh, 50,000 male and 25,000 female finishers of the Vasaloppet 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% 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 or five or six year increase in life expectancy, uh, you know, among the people who, who got a substantial amount of physical activity or structured exercise, either one.
- PAPeter Attia
Yeah. And I, I think the, the sort of take home point for the listener is the unlike nutritional epidemiology where the risk increases and risk reductions are very, very small and they're never consistent, right? They, you know-
- MJMike Joyner
Right
- PAPeter Attia
... I mean, there's some things that are consistent and consistently small. Uh, for example, you know, 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 wanna kinda talk about it with-
- MJMike Joyner
Right
- PAPeter Attia
... exercise Um, and this is where the natural experiments are much better on the exercise front than they are on the nutrition front.
- MJMike Joyner
Right.
- PAPeter Attia
You see, going back to the example you gave, which is a very famous one of the, uh, the, the, the guys running up and down the buses, the sort of conductor guys-
- MJMike Joyner
Yeah
- 14:33 – 19:06
The Centenarian Olympics and other ways to mitigate age-related decline in strength and stability
- PAPeter Attia
So, so kind of one of the ways we try to get around this idea of the sort of 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 Centenarian Decathlon, 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 the math easy and say, oh, that's gonna be 79 to 89 or 81 to 91. You're in your marginal decade. What are sort of the athletic, uh, 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.
- MJMike Joyner
Right.
- PAPeter Attia
And, uh, th- they're very specific, right? So it's like walking three miles in one hour. You know, 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 with-
- MJMike Joyner
Yeah
- PAPeter Attia
... 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, you know, 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-
- MJMike Joyner
Right
- PAPeter Attia
... 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-
- MJMike Joyner
Right
- PAPeter Attia
... nutrition, certainly any medication. Uh, and, and so that to me, that's really what healthspan comes down to. It's-
- MJMike Joyner
Right
- PAPeter Attia
... it's not just I'm not disabled, but it's I'm really thriving.
- MJMike Joyner
Yeah, I'm engaged. I can engage in what I want to engage in. Yeah, and I, I think, Peter, you've hit the nail on the head. And, and I think that, that what we see, uh, in those decades, it... there's... what's really instructive is if you look at, uh, the decline in performance in age group swimming, running, cycling, uh, rowing, really a- any, any sport where there's pretty good record keeping, is people can start to decline at age 30 without training. Uh, you can push that back to age 40 with training, in other words, if you work out every day in, in- intentionally and, and relatively hard. But then something happens to people in their middle 70s where there seems to be a, a, you know, kind of a, a more, a steeper rise. And what's interesting about that steeper rise is it, it seems to shift from sort of a cardiopulmonary limitation to sort of a skeletal muscle strength/frailty situation. And, and what you described in terms of getting up off the floor, I think something like 70 year-- 70% of 70-year-olds can't get off the floor, not one hand, two hands, just can't get off the floor.
- PAPeter Attia
Yep.
- MJMike Joyner
And, and you start looking at... and, and we both know from, from being doctors, if you look at what happens when a person in that age group falls, it's just no fun. So, so-
- PAPeter Attia
Yeah
- MJMike Joyner
... if you look at, at, at, at what really takes people out, it's things like falls, it's inability to, to, to, to do things. And so what happens is, is, is, uh, you know, walking three miles in an hour takes some cardiopulmonary, uh, capability, but not a ton, just some. But whereas being able to go up, uh, you know, the stairs takes more, being able to get off the floor takes more. So I think, uh, one of the things that people have to think about, especially as they get into their 40s and 50s, is, is adding strength or some sort of circuit training and agility training to their program. And so I, I think you've hit the nail on the head. And one of the things I do is, is I'm 63, almost 64, is I have the jump rope my mother gave to me when I was 14. She gave me a beautiful boxer's jump rope, leather with ball bearings in the works, you know? And I, I carry it with me when I travel because, uh, you can always jump rope, even if it's out in the parking lot of a hotel. You can ... People think you're nuts, but it's, uh, you know, uh, uh ... But it works. It's a terrific, terrific exercise.
- PAPeter Attia
It, it actually is for a number of reasons, including foot reactivity, which is also-
- MJMike Joyner
Correct
- PAPeter Attia
... one of those things that can cont- you know, the lack of foot reactivity is something that can contribute-
- MJMike Joyner
Correct
- PAPeter Attia
... to the fall. So you're, you're getting the cardio benefit, the coordination benefit, and also this-
- MJMike Joyner
Correct
- PAPeter Attia
... this, this gentle foot reactivity without ... And it depends if you know how to skip like a boxer. You don't have to really pound your knees as well.
- MJMike Joyner
Correct. And, and the other thing is you do that with some body weight, you know, some, some things as simple as pushups or, or planks, and if there's a place to do some pull-ups, uh, you're good to go.
- 19:06 – 22:39
The violent dropoff in strength and activity with age and how exercise preserves fitness in old age
- PAPeter Attia
Yeah. There's so many things you said there, Mike, that I wanna go back on and just make sure people-
- MJMike Joyner
Sure
- PAPeter Attia
... really capture 'cause it's so important. Um, uh, there's ... And I ... And we'll probably find the study and I'll link to it, but there's an amazing study that demonstrates, um, l- like, muscle mass changes, strength changes-
- MJMike Joyner
Right
- PAPeter Attia
... 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-
- MJMike Joyner
Right
- PAPeter Attia
... what you're watching. And at, it's at that cliff where physical activity level declines like this. It just goes boom. Muscle mass goes doom. Strength, doom. Same thing. And, you know, of course it begs the age-old question, right? Is the patient-
- MJMike Joyner
Yeah
- PAPeter Attia
... 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. Um, which one's the first insult? Uh, I suspect it's probably the loss of strength that contributes to the loss of activity, but then I think those feed back and accelerates this thing.
- MJMike Joyner
You really get into a death spiral.
- PAPeter Attia
Yeah.
- MJMike Joyner
And, and I think y- that's why it becomes important to keep exercising relatively hard as you get older, at least a few days a week, to, 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, in the '40s and '50s, who remained active as, uh, many of them were woodsmen and, and lived in the, in the countryside, remained very active skiing and so forth. They were studied into the, in their 80s. Now, you could argue that there was something special about these guys to begin with or they would not have become, uh, you know, champion, champion athletes, but their rates of decline were, were quite modest and, uh, more importantly, um, y- you know, their, their, their fitness levels were similar to what you would see in, in people in very early middle age. The other i- interesting thing about that is the classic studies from the 1960s. Um, these fighter pilots, you know, m- Navy and Marine and Air Force fighter pilots were sent into outer space. These were incredibly fit guys. They'd go up, up for a week and come back completely atrophied, couldn't stand up, and really in bad shape. And in '66, NASA commissioned, uh, folks at, at, in, at the University of Texas, uh, Southwestern Medical Center in Dallas to put five college-aged males, two athletes, in bed rest. And, and they had tremendous reductions in their, their fitness over just three weeks of bed rest. And interestingly, Ben Levine and his group, uh, in Dallas, along with the late Jerry Mitchell, brought these same men back 30 years later, so now they were, you know, early 50s. And it's incredible, but th- three weeks of bed rest, uh, you know, caused losses of physiological function associated with 30 years of aging. So, so it's an incredible-
- PAPeter Attia
Wow
- MJMike Joyner
... study and, and, and that's one of the things that is instructive, uh, those sorts of small studies, and that's why it's so important to, to just avoid inactivity of, of any type. And whether it's low-grade physical activity, whether it's walking the dog, whether it's gardening, whether it's, you know, taking a flight of stairs once in a while or intentional working out, it's really the way to go. And, and as you point out, really, really i- i- in those lifestyle factors you mentioned, really sort of overwhelms things, over- overwhelms almost everything
- 22:39 – 28:08
Benefits of exercise on mortality and fracture risk, and the interplay of nutrition and exercise
- MJMike Joyner
else.
- PAPeter Attia
Yeah. You, you mentioned and alluded to the danger of a fall in, in later life.
- MJMike Joyner
Yes.
- PAPeter Attia
And, um, this is something we've been doing a lot of research on internally, um, given our concern around bone mineral density in the aging population.
- MJMike Joyner
Yep.
- PAPeter Attia
Um, the mortality when-
- MJMike Joyner
Yeah
- PAPeter Attia
... 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, uh, at one year, depending on the study, it can be-
- MJMike Joyner
Yeah
- PAPeter Attia
... you know, as low as 25%, as high as 60%. Um-
- MJMike Joyner
Yeah. The magic number is usually around 40, 50.
- PAPeter Attia
Yeah. A- again, it's ... I want people to understand what we just, [laughs] what we just said. You take all the 65-year-olds and you look at those who fall and the fall results in a, 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.
- MJMike Joyner
Correct.
- PAPeter Attia
And-
- MJMike Joyner
Correct. And, and the other half aren't ... The other half, it's not like the other half are, are, uh, you know, uh-
- PAPeter Attia
Yeah. They're not, they're not back to themselves necessarily.
- MJMike Joyner
No, exactly, you know. And, and that's exactly right. So you, you wanna avoid a major health like that for sure. You know, and the other thing, Peter, there's a couple other things that have really hit me as we've talked. One is, is this man named Lester Breslow, who was this very famous epidemiologist who, who, um, died in his late 90s, was at UCLA for many years, and he studied people in, in Oakland in the late '50s and early '60s who made it to 90. A- and the sorts of four or five, uh, things you talked about, he, he identified the people in Oakland who made it to 90, and they were non-smokers. They weren't obese. They remained physically active. They ate modestly. They stayed engaged in life, and there was just five or six things that they did. And 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. Not so-- They weren't as, as focused on the small molecules, but, but, but exactly what you've described. And then I think about, you know, we've, we've talked about natural experiments. At the Cooper Clinic, they've looked at, at people's fitness levels. Now, that's not exactly the same as physical activity, uh, but, but in general, the fittest people are also the most active. And they divided people into three or four groups of fitness and then had them look at a so-called healthy eating index. So, you know, were you a junk food junkie, did you eat okay, or were you really conscious of your diet? And, and the healthy eating index, uh, in people that weren't particularly fit did have something to do with all-cause mortality. But among, among the fittest people, there was very little impact of, of diet on, on, on the outcomes, which is sort of interesting. It always brings me back to the famous quote in a, a book about distance running called Once a Runner, where somebody said, uh, you know, "If the furnace is hot enough, you can burn anything, even Big Macs." Now, you have to take that with a grain of salt, but-- Or I guess if we're worried about diet, maybe not a grain of salt. But, but, uh, but I think it does kind of give you the take-home message, but just about what a powerful thing exercise is.
- PAPeter Attia
I, I completely agree, and, and I know it's very, um... 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.
- MJMike Joyner
So w-
- PAPeter Attia
It's-- But it's pretty hard to do, and most people don't understand the amount of running that's needed to do it.
- MJMike Joyner
Well, yeah. Yeah, yeah, yeah. That's great because, you know, again, I'm, I'm looking up these studies. So I've, I've looked up these classic studies like that. And so, so there, there's this incredible study from the '50s of, of people who worked at a jute plant in, in, uh, India, and they categorized people on incredibly physically active, you know, doing manual labor, hacking away on, on, on jute to make, I think, linen or, or rope. They were gonna make rope with this stuff, all the way to office workers. And as you got, as you got more and more, uh, physically active, people got lighter. As you got more inactive, they got heavier. But what was interesting is, is people that were in the middle, middle kind of rung of occupational physical activity also had slightly lower caloric consumption and re- and remained very trim. So certainly, you know, um, if people are physically active enough, if you read the old papers about what lumberjacks were eating, you know, uh, when they were chopping wood all day long, I mean, it's 5,000, 6,000 calories a day. Uh, the, the Old Order Amish who walk around and do manual labor all day long and don't have, you know, don't have, uh, don't have tractors and stuff like that, they eat an awfully lot, and, and very few of them are obese. So, so I, I think you can outrun a bad diet or can out exercise a bad diet in a modern, uh, high calorie, low physical activity world, I think, is the caveat that has to go to that one.
- PAPeter Attia
Yeah. And yet when you look at athletes that are doing insane amounts of exercise-
- MJMike Joyner
Oh, yeah
- PAPeter Attia
... most of them have a hard time keeping on weight.
- MJMike Joyner
Well, there, there's... Yeah, there's a terrific study about the Tour de France, you know, where, where, where they get done every day, and they're, they're just handing them food. And, um, you know, these people are eating ad lib 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.
- PAPeter Attia
Yeah.
- MJMike Joyner
Some... A- and they have a hard time keeping their weight, weight, uh, uh-
- PAPeter Attia
Yeah, they, they, they be-- They are catabolic throughout the tour.
- MJMike Joyner
Correct.
- PAPeter Attia
And they, they finish-
- 28:08 – 30:40
How exercise benefits the autonomic nervous system and why this plays an important role in our health
- MJMike Joyner
weeks.
- PAPeter Attia
So let's go back to something you said at the outset-
- MJMike Joyner
Yep
- PAPeter Attia
... which was the impact of exercise on the autonomic nervous system.
- MJMike Joyner
Correct.
- PAPeter Attia
Uh, explain to folks what the autonomic nervous system is, how it differs-
- MJMike Joyner
Right
- PAPeter Attia
... from the sympathetic nervous system, and why it plays such-
- MJMike Joyner
Right
- PAPeter Attia
... an important role in our health and, of course, how exercise impacts it.
- MJMike Joyner
W- when we think about the nervous system, normally we think about our brain, our eyes, our ears, and, and our senses and also our ability to grab things, move our muscles, that sort of thing, and, you know, feel pain or feel heat or cold or, or, or, or sense the environment. But your autonomic nervous system is what controls your internal environment, and, and that's called the, you know, the milieu internal or, or whatever is, is from the French a long, long time ago, and it's called homeostasis. So, so, you know, we can increase our metabolism 10 or 20 fold with exercise, but our, our body temperature only 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 are the sympathetic nerves and the parasympathetic nerves, and these used to be kind of categorized as fight or flight. And you would either, you know, uh, uh, activate especially the sympathetic nerves if you needed to fight, fight or flight, 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 and a yin and a yang between the two that happen all the time. But the, the parasympathetic nerves, and the most notable one is the vagus, they control, uh, 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. Uh, and, uh, th- that's one side. The other side is the autonomic nervous system, nerves that increase your heart rate, uh, stimulate your, your blood vessels to constrict, st- uh, help your muscles contract harder, and also do things like make you sweat. And so that's, that's really, uh, uh, the difference betw- between the autonomic, uh, or the, the parasympathetic and sympathetic branches of the autonomic nervous system. 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, uh, a bit better tuned up, it, it can do a better job regulating your internal environment, the classic example being, for exam-- your, your blood pressure.
- 30:40 – 35:31
VO2 max, heart rate recovery, heart rate variability, and other metrics of fitness positively impacted by exercise
- PAPeter Attia
Now of course, what everybody knows, and we're gonna talk in a moment about VO2 max testing and how-
- MJMike Joyner
Yeah
- PAPeter Attia
... that's done 'cause I wanna get into the weeds on that. But w- when we have our patients tested, uh, you know, we have a protocol. We look at their-
- MJMike Joyner
Right
- PAPeter Attia
... blood pressure before, and then we look at their blood pressure throughout. Um, and then we wanna look where they are percentile wise at the-
- MJMike Joyner
Yeah
- PAPeter Attia
... at the max exertion, what's their blood pressure. And, um, without exception, a person's blood pressure goes up when we do a v- a VO2 max test.
- MJMike Joyner
Correct.
- PAPeter Attia
So you take somebody whose blood pressure is 115 over 75 at the outset, they'll easily be 160 over-
- MJMike Joyner
Yeah. Oh, yeah
- PAPeter Attia
... you know, 95 or 100, and that's completely normal and healthy at a max.
- MJMike Joyner
Even higher if they're, if you measured it while they were weightlifting.
- PAPeter Attia
Yeah. Yep, exactly. Right. So, so explain to folks why it is that during exercise nothing looks good, right? Blood pressure's high, heart rate's-
- MJMike Joyner
Yeah
- PAPeter Attia
... high, heart rate variability is low. What is it about the recovery phase from exercise-
- MJMike Joyner
Right
- PAPeter Attia
... that produces a net positive effect even though in the moment exercise presumably is doing things-
- MJMike Joyner
Right
- PAPeter Attia
... that are not necessarily in our body's best interest in the, in that moment?
- MJMike Joyner
I would say they are in their best interest because what happens, Peter, is, is the system, uh, shifts a little bit to kind of meet the demands of the skeletal muscle. You gotta be able to contract the muscles to exercise. And again, that's sort of consistent with the fight or flight thing. If you're gonna run away or, or be in a fight, you wanna be able to contract your muscles. And so to, to do that, you need to, 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 gotta do is increase the pumping function of your heart. At rest, people's, uh, you know, heart is beating about five liters or a little over a gallon a minute. Uh, during, you know, moderate exercise, it can be, uh, you know, 10 liters a minute. During heavy exercise, 15 or 20. And in elite athletes, uh, who are, are, are very trained and have 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, uh, to think about and, and to, to, to, to, 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 gonna wanna increase your heart rate. So that's what happens. But then when you stop, as you mention, heart rate falls, blood pressure falls, and, and things look probably better than they did, uh, in somebody who is untrained and hasn't exercised.
- PAPeter Attia
What do we know about the rate of recovery, Mike? There's-
- MJMike Joyner
Right
- PAPeter Attia
... something called heart rate recovery, HRR-
- MJMike Joyner
Right
- PAPeter Attia
... that is a pretty interesting metric. Um, tell, tell us what we know about HRR.
- MJMike Joyner
So people do a maximum exercise test, and their heart rate's, you know, 150, 160, 180, whatever their age is, and, and, you know, 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 does your heart rate go back down to, to some number? You know, does it, how fast does it get till it's under 100? How fast till 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 that means that, that, that... uh, and this nerve also, uh, i- is, is- suppresses funny heartbeats and is protective when it's, when it's in good shape against, uh, you know, uh, arrhythmias and, and ventricular tachycardia, ventricular fibrillation, sudden death, 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 the, or, or vagal activity. And, and, and that's a good thing.
- PAPeter Attia
Now heart rate variability can be quite, quite genetic, right, Mike? The, 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. Is that... Have you found that to be the case?
- MJMike Joyner
You know, I, I would say a- again, it depends on h- on what sorts of training people have been doing, what they're, th- what, what they've been exposed to. But, but in general, you know, most people can get a nice training bradycardia, which again is vagal tone, and most people if they're trained can, can, uh, go from, you know, slow heart rate recovery to fast heart, faster heart rate recovery and, and, and also have more heart rate variability. So I think, I think worrying about the differences in the initial baseline, Peter, while interesting and what they might be attributable to, is probably less important, uh, than the fact that, that they're modifiable, as you mentioned very early, uh, you know, as they say at the top of the show.
- 35:31 – 44:04
Reduction in all-cause mortality with increased fitness levels and VO2 max
- PAPeter Attia
Yeah. So let's talk about this VO2 max test 'cause we're gonna talk about-
- MJMike Joyner
You got it
- PAPeter Attia
... what it means and, and, you know, how predictive it might be of an individual's, uh-
- MJMike Joyner
Mm-hmm
- PAPeter Attia
... mortality. So let's just start by, um, explaining to people what you do when a person comes into the lab.
- MJMike Joyner
Right. 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 gonna measure it directly and, and either a face mask or a, uh, mouthpiece that they breathe. And that allows us to measure how much oxygen they breathe in or h- air they breathe in and 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 three and a half mLs per kg per minute, so think about, you know, or, or maybe 250 mLs or 300 mLs, so like 10 or 12 ounces of oxygen per minute Right? And an unfit, you know, person in their 30s or 40s can typically increase that about eight or 10-fold to say in a, in a, in to, to say, uh-
- PAPeter Attia
30 or 35
- MJMike Joyner
... yeah, to 30. And that would be, that would be 30 or 35 or about three liters a minute, right? And with training, most people can increase things at least 10 or 20%. And if you have some ability and/or you train very hard, some people can almost double it. And so what happens is that once your VO2 max goes up, again, just like physical activity, it's a measure of, of physical fitness, and it's also linked to all-cause mortality. So peop- the fitter you are, the, the lower your chance of dying in the next year, two years, five years, 10 years. And it's, it... For many years they thought the thing sort of plateaued at what they call about 10 or 12 METs. A MET mean your resting metabolic rate. So you had to be able to get 10, 10 METs, and 10 METs is being able to run one mile in about 10 minutes, roughly, for the average person. And, and now people have shown a group in, in, in Henry Ford in Detroit have shown that that continues to rise even up to 15, 16 METs. So people that are quite fit continue to, to, to gain, uh, you know, benefit in terms of all-cause mortality. I mentioned the, the cross-country skiers earlier, and while they didn't do VO2 max tests 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 longest period of time and probably were the fittest, also had lower, lower all-cause mortality than people who had not, not compared to sedentary peers, but compared to people who'd done a few races a little bit slower. So yeah, peak fitness matters.
- PAPeter Attia
Yeah. When we look at that, that... There- So there's a paper in JAMA that I think is by far the most-
- MJMike Joyner
Yeah
- PAPeter Attia
... compelling, uh, description of this phenomenon. A couple things are noteworthy about it, and I, I've talked about this in a previous AMA-
- MJMike Joyner
Yep
- PAPeter Attia
... 'cause it's, it's really one of the... I would consider it one of the 10 most influential pa- papers that I, um, ha- have read in terms of changing how I think about, uh, you know, healthspan and lifespan. Um, as you said, the relationship is monotonic and it does not plateau. So-
- MJMike Joyner
Correct
- PAPeter Attia
... it's... That's a, that's an important thing to, to appreciate, which is this is a more is better phenomenon, and very few things in physiology are more is better.
- MJMike Joyner
Yeah.
- PAPeter Attia
Usually physiology behaves in Us and upside down Us or maybe Js and things like that.
- MJMike Joyner
Yeah. Or, or, uh, yeah, S shapes-
- PAPeter Attia
Or plateaus
- MJMike Joyner
... or whatever we have.
- PAPeter Attia
Yeah, S shapes
- MJMike Joyner
Correct. Yep
- PAPeter Attia
Exactly. Sigmoid curves. But this is not the case here. This study that we're talking about put people into the bottom 25th percentile, you know, 25th to 50th percentile-
- MJMike Joyner
Yep
- PAPeter Attia
... 50th to 75th, and then the last group it basically divided into, you know, 75th to 97 and a half, and then they had that little sliver of people that they called-
- MJMike Joyner
Right
- PAPeter Attia
... elite that were at the top two and a half percentile. And all-cause mortality just went lower and lower and lower and lower.
- MJMike Joyner
Correct.
- PAPeter Attia
And if you looked at the hazard ratio the other way, 'cause we often think about hazard ratios and risk reduction, but if you look about it in risk increase, when you compared the people in the top two and a half percent, uh, of the VO2 max to the bottom 25%, the hazard ratio moving in that direction was 5.04-
- MJMike Joyner
Yeah
- 44:04 – 51:33
Does the relationship between exercise and longevity follow a J-curve?
- PAPeter Attia
Mike, one of the things that we've looked at a lot internally, um, is the, the literature that argues a different point, uh, the literature that argues that-
- MJMike Joyner
Yeah
- PAPeter Attia
... in fact, there's a J curve here.
- MJMike Joyner
Right.
- PAPeter Attia
And we all agree that a person who doesn't do anything is at the highest risk.
- MJMike Joyner
Right.
- PAPeter Attia
The literature is so unambiguous there, it doesn't warrant any further discussion. But, um, now... let's now look at the addition of work. Now, you and I, I just wanna make sure the, the, the listener understands the way we're gonna talk about this. Let's talk about these in MET hours per week. So-
- MJMike Joyner
Yeah, right
- PAPeter Attia
... you've already done a great job explaining-
- MJMike Joyner
A, a weird, a weird [laughs]
- PAPeter Attia
A, a weird... I, I've actually had to convert my own training-
- MJMike Joyner
Yeah
- PAPeter Attia
... into a MET hour per week spreadsheet-
- MJMike Joyner
Yeah, right
- PAPeter Attia
... so that I can interpret what I do in the context-
- MJMike Joyner
Yeah, yeah, yeah
- PAPeter Attia
... of all the literature.
- MJMike Joyner
A, a weird metric for sure.
- PAPeter Attia
Totally weird, but let's explain to people what it is, right? So you c- so you've, you told us what a MET is. One MET is the metabolic expenditure of sitting-
- MJMike Joyner
Right
- PAPeter Attia
... at rest, which corresponds to about 3.5 milliliters per minute per kilogram-
- MJMike Joyner
Yeah
- PAPeter Attia
... of m- minute ventilation. So, uh... or actually VO2-
- MJMike Joyner
Oh, excuse me. Yeah
- PAPeter Attia
... so oxygen ventilation, not-
- MJMike Joyner
Correct
- PAPeter Attia
... pulmonary ventilation. Okay. So then let's talk about how that ramps up, right? So if you, if... How many METs is it, Mike, to walk three miles in an hour? That's, that's two-
- MJMike Joyner
Oh, probably four, five, six, something like that.
- PAPeter Attia
Oh, is it that high?
- MJMike Joyner
I don't know.
- 51:33 – 1:01:51
Mitigating age-related decline in fitness by elevating your VO2 max at a young age
- PAPeter Attia
The other thing I think that argues in favor of, uh, or sorry, argues against-
- MJMike Joyner
Yeah
- PAPeter Attia
... the J-curve is the VO2 max data that we just discussed-
- MJMike Joyner
Correct
- PAPeter Attia
... which is an enormous cohort, probably the largest-
- MJMike Joyner
Yeah
- PAPeter Attia
... cohort after the-
- MJMike Joyner
Correct
- PAPeter Attia
... Copenhagen cohort, and far more balanced in terms of the number of people in each group.
- MJMike Joyner
And b- has been repeated in other populations.
- PAPeter Attia
Yeah. And so, 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-
- MJMike Joyner
Right
- PAPeter Attia
... by a long shot if they're not training significantly?
- MJMike Joyner
Correct.
- PAPeter Attia
Because I, you know, I, if you... I look at... I know those numbers very well. I mean, we, we p- we put all of our patients up against that template, and we show them where they are and where we want them-
- MJMike Joyner
Yep
- PAPeter Attia
... to be. Um, and we actually hold them to an even higher standard, Mike. We kinda want our patients to be at the elite level for a decade below where they are, actually are age-wise
- MJMike Joyner
Correct
- PAPeter Attia
... and, and I'll tell you in a moment why we do that. I wanna see if you agree with my logic. But I just, you know, having b- been training my whole life, I can tell you, I, I don't see how you're gonna get there doing 40 met hours per week. Like, you, you can't-
- MJMike Joyner
Yeah
- PAPeter Attia
... achieve a VO2 max of that level just doing a little bit of, you know, maintenance stuff here and there. I mean, you, you have to be training.
- MJMike Joyner
Yeah, you have to be training. You have to be doing some high-intensity training, so I agree with you. And, and the other thing is if you look at some classic studies by people like, uh, Bob Hickson and more recently Wisløff's group up in Norway, you know, people who do some longer intervals three or four times a week can get a lot of bang for their buck in terms of VO2 max.
- PAPeter Attia
Well, I wanna, I wanna come back to that, Mike, 'cause I wanna talk very specifically about the-
- MJMike Joyner
Yeah
- PAPeter Attia
... different modalities for training. Before I do, I wanna see if you can check my logic on this.
- MJMike Joyner
Okay, sure.
- PAPeter Attia
A big part of where we come up with the reason you wanna have a high VO2 max when you're young is we wanna be able to prepare for the inevitability of decline.
- MJMike Joyner
Right.
- PAPeter Attia
So I wanna start by just asking you, what, what is the most up-to-date, uh, understanding of how much, uh, peak-
- MJMike Joyner
Right
- 1:01:51 – 1:08:43
Breaking down the variables that drive VO2 max
- PAPeter Attia
Let's talk a little bit about VO2 max again-
- MJMike Joyner
Yeah
- PAPeter Attia
... in terms of like what is actually driving it. So let's go through all the variables, right?
- MJMike Joyner
Right.
- PAPeter Attia
So you've got sort of gas exchange in the lungs.
- MJMike Joyner
In the lung, correct.
- PAPeter Attia
And then you've got gas exchange in, uh... Or sorry, then you have pump efficiency, right? So we-
- MJMike Joyner
Correct
- PAPeter Attia
... we went through the mechanics of that again, but just so people understand what we talk about. You've got stroke volume, contractility-
- MJMike Joyner
Right
- PAPeter Attia
... of course, afterload and preload and all of these things-
- MJMike Joyner
Yeah
- PAPeter Attia
... 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.
- MJMike Joyner
Right.
- PAPeter Attia
So, so broadly speaking, let's just say those are-
- MJMike Joyner
Right
- PAPeter Attia
... 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. Uh, w- is that... I know that's overly simplistic.
- MJMike Joyner
Yeah, it's a way to look at it. So let's-
- PAPeter Attia
Yeah
- MJMike Joyner
... just think. You got air to lung.
- PAPeter Attia
Yep.
- MJMike Joyner
Lung to blood, blood from the, the, the heart to the tissues, uh, and, and oxygen from the blood to the tissues, right? So there's y- there's four or five steps like that, and you enumerated the, you know, the three big ones. And so in general, you know, oxygen uptake is, 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. And 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 f- how, how much blood can you pump? And, and 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 with 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, and so the key is delivery.
- PAPeter Attia
Mm.
- MJMike Joyner
And that's heart rate times stroke volume. And, and interestingly, Peter, as you, I'm sure you've seen, is some of your fittest people actually have slightly lower peak heart rates, and one of the reasons is, is 'cause their stroke volume is so, so, uh, so high. One of the really interesting, again, experiment of nature patients is, or, or subjects is a man called Eskild Ebbesen, who won gold medals in five Olympics in rowing for, for Denmark.
- PAPeter Attia
Wow.
- MJMike Joyner
And, and they have serial VO2 max data on him from the time he was 18 or 19 till his early 40s, and his VO2 max stayed around, you know, 5.6 liters per minute, which is quite high.
- PAPeter Attia
Wow.
- MJMike Joyner
And he weighed about 70 kilos, so he... I, I believe he was a lightweight rower. And anyways, uh, but his peak heart rate dropped from about 190 to 1, 1, uh, 50 over that period of time, which all that means is for, is that he was able to pump the same amount of blood, but he had to do more with each beat. And, and that's a, that's sort of an interesting example, but the, the data on, on-
- PAPeter Attia
That, that's an insane example, actually.
- MJMike Joyner
Yeah. Yeah. And again, th- these are the sorts of things you, you, you see. So, so that is really the key. A- and if you look-
- 1:08:43 – 1:19:02
Learning from elite athletes: Training regimens, aerobic efficiency, and other impressive metrics
- MJMike Joyner
big pumps.
- PAPeter Attia
All right, so let's talk a little bit about the training. So, so, um, l- let's, um, let's start with something that we haven't talked about, which, you know, when you look at the best, you know, high-output endurance athletes today, you know, it's, 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. [smacks lips] You know, I've had Iñigo San Millán on the podcast twice, and we've talked at length about, uh, Tadej Pogačar, and it's, it's, it's amazing to talk about how hi- how high his FTP is, his functional threshold power.
- MJMike Joyner
Yeah.
- PAPeter Attia
We can talk about his VO2 max, but equally amazing to that is how much power he can put out while keeping lactate below two millimole.
- MJMike Joyner
P- right, right, right, right.
- PAPeter Attia
And, and, and, you know, I think he's at four... Oh, he's over four watts per kilo-
- MJMike Joyner
Right
- PAPeter Attia
... while keeping lactate before, below two millimole.
- MJMike Joyner
Right.
- PAPeter Attia
And, and what, why that's amazing for someone who doesn't ride a bike is you... 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-
- MJMike Joyner
Yeah, correct
- PAPeter Attia
... couldn't do it for a minute, and this guy-
- MJMike Joyner
Correct
- PAPeter Attia
... can do it for four hours.
- MJMike Joyner
Correct.
- PAPeter Attia
So, so, so 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, your peak. Do you agree with that sentiment?
- MJMike Joyner
So w- what I, what I would simply say, Peter, you know, as we think about performance and you think about these elites, we think obviously about their VO2 max. Then you start thinking about, you know, well, their 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 in arguments with people about the details, but what fraction of, of your VO2 max can you perform at for, you know, minutes to hours?
- PAPeter Attia
Extended... Yeah, exactly.
- MJMike Joyner
Yeah. And so, you know, t- and, and typically, it's about 60% in untrained, kind of young to middle-aged people, uh, lower in people that are, are really untrained. Uh, but, but just, just sort of sedentary. People that are, are, are very fit, it can be 75, 80, 85, even 90%-
- PAPeter Attia
Mm
- MJMike Joyner
... of VO2 max, and in some older athletes, close to 100. So, so that's exactly what you describe. Somebody like that probably has a, you know, a, a peak work rate that they could sustain for 10 or 20 minutes of six, seven, uh, watts per kilo. So the fact that they can do four watts per kilo forever shouldn't surprise anybody, and that's just like you, you look at somebody like Mr. Kipchoge, you know, who's running 440 miles at, at a, at a, at a, a pace that doesn't really probably cause much of an increase in his blood lactic acid levels at all.
- PAPeter Attia
Did they ever reveal any of those metrics, that he-
- MJMike Joyner
Yeah, that data's, that data's been published now.
- PAPeter Attia
So t- tell me, what was his lactate level at the completion of the two-hour, of the just under two-hour marathon?
- MJMike Joyner
Well, remember, remember, at the end of, of the race, you wouldn't have a lot of carbohydrate on board, but-
- PAPeter Attia
Yeah
- MJMike Joyner
... but I would just simply say he can run 440 miles or over 12 miles an hour at, at, at, you know, substa- at levels that barely nudge his lactic acid levels.
- PAPeter Attia
[laughs]
- MJMike Joyner
Barely nudge them. But, but, but remember too, but his VO... Uh, but, but he... And what's interesting is, is when I first started thinking about this and making models of performance, I, I thought the, the highest number was 85% of max, and it's probably closer to 90 for somebody like him. Uh, but, but, but the, the other interest, so, so the... A- and when you were talking about FTP for one minute, the other interesting thing about that, uh, Peter, is, you know, the, the Kipchoge challenge, people have gone and cr- you know, put treadmills at 12 and a half-
- PAPeter Attia
Yep, I've seen it done
- 1:19:02 – 1:21:55
Health benefits of light exercise for the average person
- PAPeter Attia
Yeah, yeah. Um, so, so do you think there is a, a sort of training benefit? I know there's a health benefit, but a, a training benefit in the lowest zone. So, so we kind of think about zone-
- MJMike Joyner
Yeah
- PAPeter Attia
... two as where Kipchoge is probably spending 60 to 70% of his time. He can still talk.
- MJMike Joyner
Yeah, probably right, right at the edge of two or three.
- PAPeter Attia
Yep. And then, um, and then obviously he's in zone three, four for, you know, kind of race pace.
- MJMike Joyner
Yeah.
- PAPeter Attia
And then, and then he's like 4, 5, 10% of his-
- MJMike Joyner
Correct
- PAPeter Attia
... mileage, which is-
- MJMike Joyner
Correct, correct, correct
- PAPeter Attia
... you know, really stretching himself. Now, is Kipchoge or, or other athletes deliberately putting time into zone one, which is truly a recovery pace, or...?
- MJMike Joyner
Yeah, they do that when they're recovering, you know, between intervals. And, and y- you would be amazed at how, uh... I mean, 'cause I did it many, many years ago. Uh, you know, getting started, so the first mile or two can be very slow.
- PAPeter Attia
Mm.
- MJMike Joyner
I mean, it can be just almost a walk-jog, and then they kind of drift into it. Uh, a- and I think, but, but thinking about the listeners who are just trying to improve their health, that where, that's where you come back to physical activity, you know, versus intentional training. So, you know, you start looking at the health benefits of just kind of, uh, less than brisk walking. You know, purposeful, but not really brisk walking. They're substantial.
- PAPeter Attia
Yeah.
- MJMike Joyner
So, so I, I think, you know, people at zone one, two, you know, you know, you know, parking your car, uh, farther out in the parking lot and, and strolling in, I think, you know, walking the dog, and that can mean all sorts of things depending on what kind of dog you have and, and who's in the neighborhood, uh, you know, can, can helpful. I mean, the, the, the data on gardening. Uh, y- you know, and again, you, you could be out there, uh, hacking away weeds with a, with a machete or... but, but most of us think about gardening as relatively light exercise. So the, the health benefits of, of light physical activity, light exercise, I mean, are substantial. And remember, you're, you're correct in the sense that it, that it, at least from our perspective, there is no J-curve and things, you know, things, uh, uh, go up, but it's not completely linear. And, and, you know, the, the biggest benefit people get health-wise is the first 10 or 15 minutes a day.
- PAPeter Attia
And why do you think that is?
- MJMike Joyner
Well, I, I think that if you, if you, if you look at what 10 or 15 minutes does, I mean, I think it begins to do things in your skeletal muscle that improve your insulin sensitivity and, and help you fight against, uh, diabetes. I think just a tiny bit of additional physical activity is at least some buffer against weight gain. I think that there's some, uh, improvement in your, the lining in your blood vessels and, and probably some improvement in your autonomic function. Is, is your, is your heart gonna get bigger? Are you gonna get a, a more efficient cardiac pump? Probably not. But are you gonna begin to, to do some of the things? Uh, and the answer is yes.
- 1:21:55 – 1:31:24
Simple training metrics to track, and Mike’s current exercise regimen
- PAPeter Attia
So Mike, should those of us who really kind of care about this and care about using as many-
- MJMike Joyner
Yeah, yeah
- PAPeter Attia
... metrics as we can to understand this and, you know... 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?
- MJMike Joyner
So, you know, I think that, that, that, that... and you see it more among the cyclists than you do ag- among the runners. Uh, and, and, and is, is I think that there are people that are, you know, uh, really into tech and monitoring, and then there's sort of tech nudies.
- PAPeter Attia
[laughs]
- MJMike Joyner
I'm, I'm, I'm a, I'm a tech nudie, and, and part of the reason is, is, is there wasn't as much around when I started, and I mean, we just were getting digital watches, and they weren't even stopwatches. And, and the other reason is, is that, that at the time, one of the big innovations was rating of perceived exertion.
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
Uh, 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... 'cause, you know, you can have a good day and a bad day in terms of the metrics. So I think what's been shown i- is, is that, that they're all sort of parallel, and, and if you learn to read your own body via the, via, you know, the rating of perceived exertion and/or, or metrics, you know, find one you like and then just focus on sort of big picture things. So I would not get too hung up on heart rate recovery and too hung up on, on, um, on, uh, heart rate variability. I would just more say, "Are you... How much are you doing?" You know, uh, 30, 40, 60, 100, you know, 180 minutes a week. Are you also doing other forms of... uh, not a week, a day. Are you also doing other forms of, of activity, you know, like, uh, 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, you know, kind of a pleasant sort of pace? So I, I think that that sort of information can get you as, as much as you need, and I think the main thing then, Peter, is to make sure that, that, um, you have some accountability, whether it's, you know, with a training partner, maybe with a device or a diary, maybe, you know, with just how far did I run today? That sort of thing.
- PAPeter Attia
So, 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 is a tr-
- MJMike Joyner
No, I... So, so here's what I do is, is that-
- PAPeter Attia
I mean, that, that, but that, that's just... I don't think people understand how fast that is. I mean, to even-
- MJMike Joyner
Yeah, no, and I, I w- I once ran a 2:25 marathon, but, but, you know, the older I get, the better I was, right?
- PAPeter Attia
[laughs]
- MJMike Joyner
So here's what I do. Here's what I do, Peter, and is, is it that, like, I'm a big believer in what's called hard/easy, hard day, easy day. And, and I think that, that, that, that... and so what, what I, what I'll do ... uh, like tomorrow will be a hard day. So I'll get on, on, uh, uh, you know, a stationary bike in my, in my, uh, workout room and, and, and 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, um, uh, 15, uh, or, or really kind of 25 squat thrusts, a minute of jumping rope, static wall sit to failure, and then some drop sets where you go down, you know, where, where you, you go down the weight stack. A drop set... Then, then, then drop sets with, with, uh, incline flies, then drop sets with leg extensions, then drop sets with a combination of, of, uh, pull-ups and lat pull-downs and military press. Then some additional s- stuff for my legs, then some, uh, uh, 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, major muscle masses, and that takes about 22 minutes. And it's, it's, it's, uh-
- PAPeter Attia
22 minutes for one circuit.
- MJMike Joyner
One circuit.
- PAPeter Attia
You do. Yep.
- MJMike Joyner
Then, then I get on the bike, right? And, and I'll do, uh, like eight times, uh, uh, three minutes of a ladder where you start, you know, 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.
- PAPeter Attia
And sorry, how long do you take to ladder, three minutes?
- MJMike Joyner
Three minutes. So, so you go, like, 100 watts for something like 100 watts for 30 seconds, 150 for 30, 200 for... 200 for 30, 250 for 30, th- 300 for 30, 350 for 30, come back down.
- PAPeter Attia
Yep.
- MJMike Joyner
Times eight. And, and that, you know, and, and that takes about an hour, and that-
- PAPeter Attia
And how long in between your three-minute sets?
- MJMike Joyner
No, you just go up and come right back down.
- PAPeter Attia
You're already done. Okay, you're right. So your-
- MJMike Joyner
Yeah, so-
- PAPeter Attia
... your rest from the-
- MJMike Joyner
So the recovery is-
- PAPeter Attia
Yep, yep
- MJMike Joyner
... exactly.
- 1:31:24 – 1:39:49
How to boost your VO2 max, and the importance of form and tempo with interval training
- PAPeter Attia
So let's talk about folks who are listening to this who-
- MJMike Joyner
Yeah
- PAPeter Attia
... want to boost their VO2 max.
- MJMike Joyner
Correct.
- PAPeter Attia
Let's talk about the different protocols that exist. I'll tell you what we typically, uh-
- MJMike Joyner
Yeah
- PAPeter Attia
... tell, tell patients to do, which is kind of i- i- 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, a four on, four off protocol.
- MJMike Joyner
Yeah. No, you're right there.
- PAPeter Attia
So, so we'll-
- MJMike Joyner
Yeah
- PAPeter Attia
... tell people, um, a- and again, the easiest way that I personally can do this is on a bike on an incline.
- MJMike Joyner
Yep.
- PAPeter Attia
A- and it can't be a very steep incline. It's gotta be, like, 6% grade.
- MJMike Joyner
Yep.
- PAPeter Attia
I wanna stay in the saddle, and, but I never want the resistance to go away, and I basically-
- MJMike Joyner
Correct
- PAPeter Attia
... wanna be in the saddle climbing against resistance-
- MJMike Joyner
Correct
- PAPeter Attia
... for four minutes. And I use a power meter and a heart rate, so I just wanna keep the power as steady as I can. Invariably, it dips in about the third minute-
- MJMike Joyner
Yep. Yep
- PAPeter Attia
... 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.
- MJMike Joyner
Right. So, so it's-
- PAPeter Attia
And then it's basically just repeat that. So, so-
- MJMike Joyner
So m-
- PAPeter Attia
Yeah
- MJMike Joyner
... yeah, no, no, I'm with you. What I tell people, for example, that have come and say, "I wanna run a faster marathon, I wanna do this, I wanna do that," you know, and they're running a lot of miles, they need to get their VO2 max up. And I tell them exactly what you've described. Sometimes I tell them five minutes and three minutes rest, sometimes whatever. And people that are fitter sometimes only ta- like, I would only take two minutes of rest.
- PAPeter Attia
Okay.
- MJMike Joyner
A- and that's just y- 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.
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
Maybe a little faster, or, 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, and 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, were not going so fast, you would walk in between. So that would be the sort of thing that, that I would i- i- describe to people. And the, the classic training, you know, among elite runners is, is mile repeats. You know, people doing, you know, four or five times one mile, and then they jog a, a m- a quarter mile or a half mile in between. And I, I personally have seen [laughs] really good runners. [laughs] I mean, it's... I've seen people s- you know, do, you know, 4:30, 4:25, 4:20, 4:15 [laughs] , 4:10, 4:05, which is... But I mean, these were people getting ready for the Olympics, you know. So, so, so, but, but those sorts of things-
- 1:39:49 – 1:42:33
Training advice for the average person
- PAPeter Attia
Now, going back to our very, very-
- MJMike Joyner
Yeah
- PAPeter Attia
... recreational person who's never trained in their life, we, we don't even, we don't use lactate testing on people at that level.
- MJMike Joyner
Yeah.
- PAPeter Attia
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 b- we want you to be able to talk, but not enjoy it, right? I don't want you to be any, I don't want you to be any higher than that.
- MJMike Joyner
Right.
- PAPeter Attia
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 you to do kind of four on, four off-
- MJMike Joyner
Correct
- PAPeter Attia
... four rounds. Um, do you think that once a week doing tho- four hard intervals is sufficient to boost VO2 max?
- MJMike Joyner
It will increase it for sure, yeah, in the vast majority of people, especially if they're doing the other stuff you're talking about.
- PAPeter Attia
Uh-huh.
- MJMike Joyner
And, and I think that, that what I really like about what you describe and what people don't realize, especially when you're gonna advocate relatively hard training for citizens, is that sometimes you have to train before you can really train.
- PAPeter Attia
Yeah, that's right. You gotta train to train, yeah.
- MJMike Joyner
Yeah, you, you gotta get... And you s- certainly have seen that in some, some, uh, [smacks lips] uh, studies with, with older, you know, people that are really, you know, 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, I think you're spot on there. And I, my guess is after they, they've been able to do it for, you know, once a week for a while, you build them up to two times per week. I, 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, was a, one of the pioneers of sports medicine orthopedic surgery, and I... He's not operating anymore, but he, the last I checked, he was alive and well out in Eugene, Oregon. And, and he, he worked with Coach Bill Bowerman, you know, the, the great Oregon coach, uh, found- one of the founders of Nike, the waffle shoe guy. You know, and they got into this hard, easy thing, which is, is sort of what I do. And I, and, and, uh, y- you know, Dr. James would tell you that once people start doing more than about five or six hard, 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 you're fatigued, whether it's this, whether it's that. So I do think that, that, um, you, you know, you wanna do something literally, I mean, m- I can't remember the last day I didn't do anything.
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
You know, it's probably been, y- y- you know, years. But, but, but my guess is the, the number of times I do something hard is, you know, 120, 130 times per year. And I, and my guess is I, I never go more than a week without doing something relatively intense.
- 1:42:33 – 1:45:45
Why professional athletes have longer careers than they’ve had in the past
- PAPeter Attia
W- when you think about, about these sort of exceptional elite athletes-
- MJMike Joyner
Yeah, yeah
- PAPeter Attia
... the Kipchoges of the world, do, do you believe they have a finite number of exceptional performances in them?
- MJMike Joyner
You know, I, I think people used to sort of think that, but I think what's happened now is that, um, uh, [smacks lips] you know, people used to drift into the, into the, into the world rankings, and they'd last, you know, maybe, uh, two Olympics.
- PAPeter Attia
Yep.
- MJMike Joyner
So they'd last, uh, you know, um, 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, there's, there's, uh, two, two things that have really changed. The first is, is that, that again, sports medicine is better. Uh, so if people do get injured, they, they, they can do things about it. And I think the second thing is just it's been s- become so professionalized, is, is people can... that are really, really good can now make enough money to make it worth their while to continue. And, and, you know, you see this in terms of the age of Olympians, where, where, you know, you used to have, uh, y- 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 it was a lot of teenagers. Now, you see that drifting up, and you see people like Katie Ledecky having extended careers. You know, uh, uh, Phelps going 2000, 2004, '08, '12, and-
- PAPeter Attia
'16
- MJMike Joyner
... going to five Olympics. Yeah. That would've been inconceivable previously for swimmers, you know, because people, y- you know, people hung around and, and maybe stayed for one additional Olympics, and when they got done after college, sometimes two, but, but eventually they, they had to go do... get a job. But, but again, among the most elite who can now monetize this, people can last longer, and you see it also in, in, quote, "the major," unquote, professional sports. You know, before orthopedic surgery was good and, and so forth, and, and every knee surgery was an adventure, you know, somebody like Tom Brady, Brady, you know, if you would've got-
- PAPeter Attia
Yeah, his career would've been over in 2009.
- MJMike Joyner
A- a- and why keep... Or, or it would've been attenuated. And, and the other thing, Peter, is, is why keep... You know, if you're making $100,000 a year, why keep playing?
- PAPeter Attia
Yeah.
- MJMike Joyner
I- if you're making, you know, 20, 30 million or however, 30, whatever the number is, uh, you know, why not keep playing? A- and you look at, you look at, at, you know, again, uh, i- in, in sports like running, swimming, cycling, you know, th- there, there's less of a kind of a journeyman group. But if you look at, at, at, you know, the NBA, the NFL, Major League Baseball, the salary scales are pretty good, and if, 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 and, um, [smacks lips] uh, to do this. You know, so if, if you can be the eighth man on an NBA team and give people 15, 20 quality minutes a, a game, you know, you're gonna have a job for a long time. And again, if you're LeBron, you know, who apparently spends some huge amount of money on training, and, uh, cook, and all that other stuff, is, is, uh, is, you know, i- I mean, if you start thinking about spending X per year for, uh, an e- you know, a, a 40x paycheck, why not? Why, why stop?
- 1:45:45 – 1:54:24
Use of performance-enhancing drugs in professional sports
- PAPeter Attia
So where do you think we are today, Mike, in, um, performance-enhancing drugs in sports?
- MJMike Joyner
Right.
- PAPeter Attia
So, so cycling is probably the sport I would follow the closest of the major-
- MJMike Joyner
Yeah, correct
- PAPeter Attia
... endurance sports. I mean, I, I guess I follow swimming, uh, as well, though no- not nearly as much as I did for sort of 15 years prior.
- MJMike Joyner
Right.
- PAPeter Attia
Um, but, but y- you know, I think when you go back and look at the, the cycling data-
- MJMike Joyner
Yep
- PAPeter Attia
... uh, and I, 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 g- a graying of the line."
- MJMike Joyner
Right.
- PAPeter Attia
But there is a difference between the kinda high-octane cheating that was done in Lance's era and sort of the low-
- MJMike Joyner
Correct
- PAPeter Attia
... octane cheating that was, was done in Eddy Merckx's era when they were, you know, using a little bit of amphet-
- MJMike Joyner
Well, well, well, here's what I would say about where we are with doping. So the testing has gotten better, both in terms of the frequency of testing and the, uh, the, you know, the actual chemistry of the testing, you know, the machines, the, the analytics.
- PAPeter Attia
Yep, the ability to detect, yeah.
- MJMike Joyner
Yeah. Um, 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, there are typically many standard deviations above average for these things, and they're typically designed so there's not a lot of false, false positives. They don't wanna have any false positives. So that gives people a room t- 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 busts have been the police. So I think what I would simply say is that the era of industrial strength doping is over. You know, pe- pe- people doing like the East Germans did and androgenizing females to the extent that they really look like men. So I think that that is, is done. So I think there is still plenty of-
- PAPeter Attia
But, but sorry, Mike, you say that even in light of what the Russians did as recently as less than a decade ago?
- MJMike Joyner
Yeah, uh, and I think, I think what the Russians did was, again, relatively low dose-
- PAPeter Attia
Mm-hmm
- MJMike Joyner
... by comparison.
- PAPeter Attia
Yep.
- MJMike Joyner
So I think there's plenty of room for microdosing and, and 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, you know, for other forms of corruption. So, so but I do think that the, the industrial strength doping has largely been, quote, "stop prevented." I think there are probably a bunch of novel compounds that are out there, you know, p- small peptides that cause this to be released or that to be released, which would be very, very difficult to detect. They'd have vanishingly short half-lives 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 or, or some sort of, uh, you know, something that cause testosterone levels to go up or so forth. So, so I think that, that, um That it's a cat and mouse game, and, uh, you're always gonna... Y- I think, I think for the, kind of the big three, amphetamines, EPO/blood doping, and, and anabolic steroids/growth hormone, I think that, that the testing has gotten better, and industrial strength doping is over. I think we, we don't know what we don't know about these novel compounds, and I think what we learned from the BALCO situation is that there are all sorts of, you know, clever bathtub chemists who can make all sorts of things, you know, at home, in the garage, wherever it is, in, in, in, in, in a very unregulated environment. A- a- and the barrier to entry for that kind of a do it yourself sort of stuff is quite low. You can buy, you know, all sorts of laboratory equipment and reagents a- and all sorts of things. So you don't have to be, you know, a big pharma house to make, make interesting things.
- PAPeter Attia
Mike, how fa-
- MJMike Joyner
So that, that's why I'd say we are with doping
- PAPeter Attia
... how familiar are you, how familiar are you with, with BALCO and the, and the agents that are-
- MJMike Joyner
BALCO and Patrick Arnold.
- PAPeter Attia
Y- you know Patrick?
- MJMike Joyner
I don't know Patrick, but I know who he is. A- and the tragedy of Patrick Arnold, this tremendous, uh, you know, kind of, uh, guy with a master's degree, I believe, in organic chemistry.
- PAPeter Attia
Yeah.
- MJMike Joyner
The tragic, tragedy of Patrick Arnold, Arnold is he wasn't working for a, wasn't working for a, one of the big pharma companies making, uh, anti-aging, [laughs] anti-sarcopenia compounds. That's the... Y- you know, where he had, he had b- was making, um, y- you know, unusual, uh, uh, you know, chemical, chemically modified androgens.
- 1:54:24 – 1:57:58
Can the miracle of exercise be put in a pill?
- MJMike Joyner
thing.
- PAPeter Attia
So, so we started this discussion, Mike, by talking-
- MJMike Joyner
Yeah
- PAPeter Attia
... about the miracles of exercise.
- MJMike Joyner
Correct.
- PAPeter Attia
We went through all of these things that exercise-
- MJMike Joyner
Yep
- PAPeter Attia
... is doing physiologically, and how the net impact of these things is so profound-
- MJMike Joyner
Correct
- PAPeter Attia
... 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-
- MJMike Joyner
Yeah
- PAPeter Attia
... how can those benefits be put into a pill.
- MJMike Joyner
Exercise pill, sure.
- PAPeter Attia
Exactly. What is your level of optimism around the idea that some-
- MJMike Joyner
Right
- PAPeter Attia
... of the benefits of exercise could be, uh, basically captured by a pharmaceutical strategy?
- MJMike Joyner
So, so there's a couple things there, Peter. One is, is the, the efforts for sort- sort- sort of so- exercise mimetics so far have been primarily things that increase mitochondrial biosynthesis. So, uh, and that appears like it, it, it at least works in animal models. And, and then you always how do you translate it from one to the next?
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
But as I pointed out, exercise, sure, it makes your mitochondria better or makes more of them. But making your mitochondria better isn't gonna make your autonomic nervous system better, isn't gonna make your blood pressure better, isn't going to, um, necessarily make the lining of your blood vessels better, so on and so forth. So it's not gonna make your heart bigger, so on and so forth. So I think at least so far, at least so far, um, you know, these have been sort of one-trick ponies. And, and, and while you might be able to get some benefits for people that, that are, you know, wheelchair-bound or whatever, uh, although even those folk... I mean, people that are quadriplegics, let's put it that way, not even wheelchair-bound, uh, or, or, or, you know, can't exercise for some other reason, that may be helpful. I think the jury is really still out and, and so I th- I think that 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.
- PAPeter Attia
Mm.
- MJMike Joyner
I think more interestingly, I like to tell people, you know, at some level there's already an exercise mimetic out there. It's called the polypill. If, if you look at the data on people who get a combination one pill a day of, of low-dose statins, low-dose blood pressure meds, and maybe one or two other, other components, it, it causes, you know, pretty nice reductions in risk factors in most people, uh, because, because the, um, doses are low, the side effects tend to be low and so forth. And, and but again, none of this is patentable. You know, there's no, there's no market for it. But, but if, if, if people don't wanna exercise, can't exercise or whatever, you know, I think a, a, a, you know, a better choice than trying to find some mythical exercise mimetic is to, to use a, a polypill, which would do the same thing, should give them a statin, their cholesterol goes down, and maybe their endothelial function gets better. You, 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. So I, so I... and again, I'm not advocating this, but, but there's all sorts of data out there that, that, you know, a polypill, uh, is... it would be a, a, a early s- data and speculation and modeling suggesting a polypill is a, quote, legitimate, unquote, whatever that means, you know, p- potential public health strategy for lifestyle diseases. I would encourage people to exercise and, and, and do the sorts of things you're talking about, but I think polypills have been understudied.
- 1:57:58 – 2:00:44
Mike’s current research and questions he’s most interested in answering
- PAPeter Attia
So, Mike, what is it you're most excited about right now? Uh, you know, what is the, what is the pr- what is the question you're most interested in trying to answer?
- MJMike Joyner
I'm excited about a lot of things. So we've got some interesting data with Sarah Baker on sex differences in blood pressure regulation. I'm, I'm quite interested in, in con- you know, human performance. A- 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, over centuries, you know, millennia to high altitude, llamas, the birds that fly over Mount Everest and so forth, are left shifted. We've been doing some really cool hypoxia studies in people with rare left shifted hemoglobins.
- PAPeter Attia
Hmm.
- MJMike Joyner
I'm super interested in that, just as sort of a physiological question.
- PAPeter Attia
Ca- can you explain to folks what the right and left shift looks like on the hemoglobin dissociation curve?
- MJMike Joyner
A right shift, you know, think of a, of a, a curvilinear situation or an S-shaped curve, uh, uh, kind of a, 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.
- PAPeter Attia
Hmm.
- MJMike Joyner
Yeah. And, uh, without acclimation, 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 oxygen out of the air in their lungs at very high altitude. So we have a family of people and some other, uh, subjects that we studied, uh, that are left shifted and, and, um, it's very interesting-
- PAPeter Attia
Sorry, me- meaning there is a family of people who-
- MJMike Joyner
Oh, yeah
- PAPeter Attia
... genetically shift left-
- MJMike Joyner
There's also... Yeah
- PAPeter Attia
... instead of shift right-
- MJMike Joyner
Right
- PAPeter Attia
... under hypoxic conditions?
- MJMike Joyner
Correct. And, and there's all sorts of hemoglob- rare hemoglobin variants, and these just are not, you know, they don't... they're not like sickle cell or anything like that. So what's interesting, it's very interesting, Peter, to be sitting in the lab having somebody breathe in 10% oxygen talking to you. These left shifted people do that. It's, it's crazy. It's just wild.
- PAPeter Attia
What is the FiO2 at the top of Everest, by the way, just for comparison?
- MJMike Joyner
The, uh, the F- FiO2 at the top of Everest is, uh... well, the, the, uh, barometric pressure is about 250, so it'd be 21% of 250, so r- roughly about 50. So, so once you get it into your lung... I th- I think arterial's about, uh, in the 30s.
- PAPeter Attia
Wow.
- MJMike Joyner
Yeah. And so, so 10% would be if... a- and certainly at, at, at 15%, which is 3,000 meters, these people exercise like, like no... you know, they do fine.
- 2:00:44 – 2:07:58
Use of convalescent plasma to treat COVID-19
- MJMike Joyner
So I'm very interested in that. And then as I mentioned, uh, you know, before we went on, is through a weird collection of events, um, as, when the pandemic struck in March and early April of 2020, I somehow Uh, became the principal investigator of the US Convalescent Plasma Program, a, a program that was initially designed to facilitate in 5,000 patients compassionate use of convalescent plasma, plasma from recovered... antibody-rich plasma from recovered COVID patients that we would give to, uh, give to, uh, people who had disease, and hopefully the antibodies would help them. And there, 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, and that has been the gift that keeps giving. So at age 60, you know, 162, 63, I got kind of a, a new career in [laughs] 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, and, and, uh, 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 therapy's essential, uh, to help those folks. And, and, and I was telling you, uh, you know, I'm very happy that we've published papers in high-profile journals, but, uh, we just learned yesterday from People magazine of all places that the actor Jeff Bridges, uh, you know, The Dude from The Big Lebowski, he, uh-
- PAPeter Attia
The Dude himself
- MJMike Joyner
... The Dude himself had gotten lymphoma, gotten drugs that, that depleted his B cells, which is typical for lymphoma patients, got COVID, he could not clear the COVID, and, and responded to convalescent plasma. So that was a-
- PAPeter Attia
How, how much... What's the total volume of plasma you need to give a patient in that setting?
- MJMike Joyner
If you get really high titer stuff, 2 to 400 mLs.
- PAPeter Attia
That's a one-time treatment?
- MJMike Joyner
Yeah, typically. Sometimes we give people more, and what's been helpful, 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.
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
And those people make, uh, y- you know, really, really, uh, the, their plasma has a whole, whole lot of antibodies in them, and they're broad spectrum, so they cover all the variants, and they almost anticipate future variants because of the, of the, the way the immune system works and, uh, as, as 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, uh, less effective due to escape variants, this very high titer plasma is, is still available. So, uh, so we're back doing exercise studies. We're back writing papers about exercise and doing our regular physiology. But I, I think, um, yeah, this antibody therapy's really got, you know, took a bite out of me, and it's, it, it's, uh, it's like what, what Jim Bouton said, the great pitcher. You know, you s- spend your life, uh, gripping the ball and, and, and thinking about your grip on the ball, and in reality, it was the other way around. The ball had a grip on you.
- PAPeter Attia
[laughs]
- MJMike Joyner
So, you know, 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 'cause it's so interesting. And, and we get, uh, reports back to us from, you know, not famous patients that are very similar to what we've heard of Mr. Mr. Bridges, so we're so quite excited to pursue, uh, these solutions for our immune-suppressed patients. And I'm especially, you know, w- when I started, uh, medical school in 1982, those sorts of patients, you know, th- their life expectancy was quite low. And now our patients with heme malignancy, multiple myeloma, lymphoma, uh, leukemias, a lot of those people live a long, long time.
- PAPeter Attia
A- and so how, how long after a person, uh-
- MJMike Joyner
Yeah
- PAPeter Attia
... is infected and recovers from infection are they a suitable plasma donor?
- MJMike Joyner
Within about two to three weeks.
- PAPeter Attia
And how, how long-
- MJMike Joyner
We need to make sure-
- PAPeter Attia
And then, like, what, when does that window close?
- MJMike Joyner
Uh, it, it, certainly, uh, certainly it goes on for three or four months, uh, you know, probably up to six months, and it would probably reopen if they got boosted, that sort of thing.
- PAPeter Attia
Um, but it only, you only get sufficient antibodies from people who have had the actual infection, not from people who just go get a booster?
- MJMike Joyner
Uh, what's happened is, is, is that, that, that's been a... Initially, because there were no vaccines, we only had people that had the nor- net normal, normal infection.
- PAPeter Attia
Mm-hmm.
- MJMike Joyner
Since the vaccines have become widely available in the last, you know, almost 18 months now or, or 15, 16 months, we've now been able to get people who've had both, and those people, the people that have had both are really the, uh, super donors, you know? And, and, and we can work with those people to come back in and, and get multiple units. We collect our own blood at Mayo. We have a terrific blood bank here locally, but, but, uh, they're using it at Hopkins, they're using it at Harvard, using it at Einstein, a lot of other big places. We're working with the societies, the Food and Drug Administration, and others like the Lymphoma and Le- or Leukemia and Lymphoma Society, the CLL group, Infectious Disease, or excuse me, Immune Deficiency Foundation, to make sure that we have this available for their, for those sorts of patients. They've, 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, for, you know, uh, population differences. So that's one of the things we're, we're quite interested in. This is something people can donate. It's a way for people to give back.
- PAPeter Attia
Are, are you able to find sufficient donors? Are there enough donors that are willing?
- MJMike Joyner
Yeah, yeah, there's, they're, they're sufficient. They're, they're... A- again, because there's so many people who've been both infected-
- PAPeter Attia
Mm-hmm
- MJMike Joyner
... and broken through, there's a f- you know, 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. So, so-
- PAPeter Attia
And, and, and with plasma, do you still have to do a type and cross?
- MJMike Joyner
Yeah, you still got, it's gotta still be typed and crossed, and people-
- PAPeter Attia
Yeah
- 2:07:58 – 2:12:18
Parting thoughts on the current state of fitness and exercise in society
- PAPeter Attia
Uh, uh, last, last question, Mike.
- MJMike Joyner
Sure.
- PAPeter Attia
Um, given your long-standing history in athletics, both personally and professionally-
- MJMike Joyner
Yeah
- PAPeter Attia
... are you optimistic or pessimistic about the future of Americans based on the level of physical activity that we, we see?
- MJMike Joyner
Uh, uh, we need to do something. [laughs] We need to do something. And I think it really reflects our, our society in general. I think that you have, you know, 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, and I think we've got a whole lot of people that are, are... Things that when I was growing up in the '60s and '70s that were done through the park, park district and the school, school district, I think a lot of those opportunities are, um, are, uh, have fallen by the wayside. I, I mean, we used to ha- You know, the kids who were college athletes used to come back and have open gym a- a- all over Tucson when I was a kid, a- and there's no open gym at the high schools in Rochester, Minnesota, a rich community, in the summer. And, and I mean, the, and the advantage of open gym was, A, you know, you, you got people off the street and they were doing things, and, and, um, you got better athletes. And, and, and, and, uh, and, and, uh, you know, e- even the, the... And the police knew where we were, uh, which [laughs] would, would, which it, which they're always very pleased about. You know, if they know that they [laughs] if they know that all the high-energy boys are in one place, it makes their life a little easier as well. So, so I, I think, uh, yeah, I think it's a real problem. So, so I think we'll have these incredible performances by the kids who have access, but I think that, that what we're doing in the rest of the world is, is, is problematic.
- PAPeter Attia
Yeah.
- MJMike Joyner
And, and, uh, you know, if I could... I guess if I could do anything, uh, I'd, I'd start a, a national open gym movement, uh, you know, uh, winter, summer, whatever. 'Cause a lot of fa- we have a lot of nice facilities that are used just a, you know, a limited number of time per day.
- PAPeter Attia
Yeah. Could you imagine if you were czar and, and you could sort of do anything, and you just said, "No matter what it, no matter what your lot is in life," right?
- MJMike Joyner
Yeah.
- PAPeter Attia
"If you're a schoolchild, if you're a-
- MJMike Joyner
Correct
- PAPeter Attia
... a, a person who works in an office, if you're a person who works in the..." We somehow rearrange the day such that every person has a mandatory one-hour activity.
- MJMike Joyner
Right.
- PAPeter Attia
And you, you, you could make it exercise, right? You could make it, you, you, you can go to the gym for an hour. But, but it could also be, "Look, at a minimum you gotta go out and walk."
- MJMike Joyner
Well, you know, it's interesting you mention that because, uh, in our department, uh, y- with, with, uh, remote work and so forth, this has broken down a little bit, but we had a number of secretaries, uh, uh, terrific comm- You know, almost, I- they were all women, m- middle-aged women. And we have this huge sort of, uh, you know, s- deep bunker system at the bowels of the hospital with these huge hallways, and it's about a mile around the place. And, and these, uh, these, these folks would go down and walk at lunch, and they were literally, you know, they'd bring, bring their tennis shoes to work, and they, they would meet up with their pals, and, uh, you know, they'd go do 30, 40 minutes a day of, of laps at lunchtime, uh, with the secretaries all over the hospital. And it was, uh, I think terrific for them. Uh, yeah, I think it was a social event for them. And, and I think that they solved a lot of problems too, and, and they actually made them way more productive.
- PAPeter Attia
Mm-hmm. I believe it. Well, Mike, as I said at the outset, I've enjoyed reading your papers for-
- MJMike Joyner
Yeah, no, it's been fantastic, Peter
- PAPeter Attia
... for, for more than-
- MJMike Joyner
Put a quarter in
- PAPeter Attia
... yeah, for more than two decades, and I'll continue to do so. And it's been, it's been great to, to chat, and hopefully we can meet in person at some point and, and do one of the-
- MJMike Joyner
Yeah, I look forward to
- PAPeter Attia
... do a work- do a workout together.
- MJMike Joyner
Where, where, where, where do you live now? Austin or someplace?
- PAPeter Attia
Yeah, I live in Austin.
- MJMike Joyner
Yeah. No, Eddie Coyle at the University of Texas is a good friend of mine, so yeah, I look forward to it.
- PAPeter Attia
Yeah. Well, it's funny, I, I, I have been meaning to, to get ahold of him, and I'd like to have him on the podcast as well, 'cause I've also-
- MJMike Joyner
Yeah. Ed- Eddie's quite a guy
- PAPeter Attia
... I've also read a lot of his stuff. Yep. Yeah.
- MJMike Joyner
Eddie's quite a guy. Yeah. Exactly.
Episode duration: 2:12:18
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