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

00:00:00.000 Hey, everyone. Welcome to the drive podcast. I'm your host, Peter Atiyah. This podcast,

00:00:15.480 my website, and my weekly newsletter all focus on the goal of translating the science of longevity

00:00:19.800 into something accessible for everyone. Our goal is to provide the best content in health

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00:00:37.320 the end of this episode, I'll explain what those benefits are. Or if you want to learn more now,

00:00:41.720 head over to peteratiyahmd.com forward slash subscribe. Now, without further delay,

00:00:47.740 here's today's episode. I guess this week is Mike Joyner. Now Mike, someone I've wanted to have on

00:00:54.460 this podcast for quite some time. And I even, I think I mentioned it in the podcast, you know,

00:00:58.620 Mike's someone whose research I've been reading personally for probably over 20 years. He's a

00:01:03.800 physician researcher. He is a professor and vice chair for research in the department of anesthesia

00:01:08.120 and perioperative care at the Mayo Clinic. He's coauthored over 250 journal articles, and he's

00:01:13.220 written numerous pieces all over the place, including in magazines that maybe some of you have read in

00:01:17.280 Outside and Sports Illustrated. He also has his own website titled Human Limits, which as the name

00:01:21.280 suggests, speaks to Mike's interest, which is really around the limits of human physiology. Now his

00:01:26.800 research background is in studying how the nervous system regulates vascular systems and blood flow,

00:01:30.920 how age and sex disease states affect physiology, and understanding basically the limits of human

00:01:35.840 physiology by studying elite athletes. In this episode, we talk mostly about exercise. And within

00:01:41.300 that, we talk about how exercise helps us live longer, the importance of exercise as we age,

00:01:45.340 and how exercise compares to nutrition in terms of the impact it can have in health. We talk about the

00:01:49.640 impact of the autonomic nervous system, blood pressure, heart rate, heart rate variability,

00:01:53.100 heart rate recovery, and maximum heart rate. From there, we talk about VO2 max, we discuss how

00:01:57.420 it's measured, we talk about what leads to the decline in VO2 max as we age. We spend some time

00:02:02.880 talking about the J curve as it pertains to overexercising. Is it possible? What are the

00:02:07.160 dangers of too much exercise? We speak about how one should partition their time between training at

00:02:12.620 high intensity and low intensity. And we talk about a few other things like performance enhancing drugs

00:02:17.000 in sports, and if there's ever going to be a drug that mimics the benefits of exercise. So without further

00:02:22.560 delay, please enjoy my conversation with Mike Joyner. It is such a pleasure to be at least virtually

00:02:33.700 sitting here with you today. As I was kind of alluding to a moment ago, if I were to sort of

00:02:37.820 look at all the people I've had on this podcast so far and kind of ask the question, when was the

00:02:42.960 first time I became familiar with their body of work? You would be pretty far up there in terms of

00:02:49.980 duration. So growing up, endurance sports were always something that meant the world to me. And

00:02:55.340 once I even made that decision to go to medical school, a big part of it at least was understanding

00:03:00.020 physiology better. And so it's been 25 or 30 years that I've been reading your studies. In some ways,

00:03:07.520 it's a long time coming to finally be sitting down with you and hope to meet you in person one day.

00:03:11.980 Peter, thanks much. And it's great to be able to chance to visit with you today.

00:03:14.880 Thank you for inviting me. And I'm glad somebody has been paying attention to what I've been doing

00:03:18.900 for the last 25 or 30 years. So it's a very validating. Thank you.

00:03:22.620 Let's talk a little bit about your background. You're a physician by training. I believe you're

00:03:26.540 an anesthesiologist, correct? Correct.

00:03:28.860 You decided in medical school, you wanted to do anesthesia. You've always had a lifelong

00:03:32.420 interest in exercise and exercise physiology. Did you just view anesthesia as the most logical

00:03:38.320 conduit to better understand human physiology?

00:03:40.360 Peter, before I went to medical school, I actually volunteered to be a subject in a study on the

00:03:46.780 lactate threshold or anaerobic threshold when I was 19 at the University of Arizona. And luckily,

00:03:52.400 there were excellent physiologists there. But a couple of younger physicians came over from the

00:03:57.040 med school. And it became clear to me when I was 19 or 20 that if I wanted to have a career as a

00:04:02.660 research physiologist doing invasive studies, in other words, putting catheters in people and humans,

00:04:08.240 it might be wise to go to medical school. So this was always sort of my vision starting by age 20 or

00:04:13.040 21. And then what happened is I was thinking of going to cardiology or pulmonary medicine.

00:04:18.800 And I was working at the Tucson VA at one time doing a surgery rotation. And I saw what they did in

00:04:23.860 anesthesia, which is a lot like an exercise test. You're measuring people's breathing. You're

00:04:28.500 measuring their blood pressure, their heart rate. And you're giving them drugs that affect their

00:04:32.800 autonomic nervous system. And I've certainly done a lot of that. So I saw it as the flip side

00:04:36.260 of the same coin. It is strange though, to have pursued this vision for over 40 years now.

00:04:42.220 I remember having the same thoughts when I did my anesthesia rotation. I can't even remember if

00:04:45.640 anesthesia was a required rotation in med school. I don't think it was, but it was positioned as sort

00:04:51.760 of a very good thing to do. And I agree with that. And I had a feel that even though I think by that

00:04:56.260 point, I knew I was going to go into surgery, but I absolutely loved it as a sort of physiology geek.

00:05:03.220 I think anesthesia and critical care for that matter are both two remarkable specialties that

00:05:08.100 are the tip of the spear of what physiology is. When you think about exercise or people climbing

00:05:13.140 mountains or adapting to some unusual environment, the brainstem back there has to do all sorts of

00:05:19.040 incredible things to maintain what we call homeostasis or the internal environment in a way

00:05:24.220 that allows you to survive and thrive. In anesthesia and critical care, you turn those mechanisms off

00:05:30.140 and the physicians and the nurses really become the patient's brainstem as they regulate the

00:05:35.340 breathing of the patient, the blood pressure of the patient, the heart rate, and so forth.

00:05:39.500 So again, it's the flip side of the same coin. As soon as I saw what the anesthesiologist did

00:05:45.060 at the Tucson VA, it just sort of clicked.

00:05:48.440 So where did you go on to do your residency in anesthesia?

00:05:51.580 So at the Mayo Clinic. And so what happened is I got out of medical school in spring or early summer of

00:05:56.800 87 that I moved here. I've been here ever since. So 35 years and a couple of weeks.

00:06:03.480 Where did you grow up? Did you grow up in a warm climate?

00:06:05.420 Grew up in Tucson.

00:06:06.620 Obviously the Mayo Clinic is a great program, but presumably there were other great anesthesia

00:06:10.320 programs that weren't in the middle of a place like Rochester. No offense to those from Rochester.

00:06:14.360 So what drew you to Mayo?

00:06:16.100 I'd read this paper, a review article about skeletal muscle blood flow, the regulation of skeletal muscle

00:06:22.580 blood flow. And there were a lot of new ideas in the middle 80s about the regulation of skeletal muscle

00:06:27.500 blood flow. And the world's leading expert was a man named John Shepard, who is a very senior member

00:06:32.120 of the faculty here. And I wrote him a letter, you know, it was before email and stuff. So he was

00:06:37.500 friends with the head of the department, a man named Alan Sessler, and John took it over to him.

00:06:41.260 I wanted to be able to both do my residency and spend time in the lab. And I was able to work with

00:06:45.020 Dr. Shepard. And our department and our residency program were very research friendly.

00:06:50.700 So that's really why I decided to come to Rochester, but I thought I'd stay, you know,

00:06:54.660 three or four years and go back to Doosan. So that obviously didn't happen.

00:06:58.320 Let's talk about exercise. People who listen to this podcast know that I'm really passionate about

00:07:03.420 this idea of longevity. We think about longevity through the lens of five sort of modifiable

00:07:09.020 behaviors, exercise, sleep, nutrition, emotional health, and all the tools around distress tolerance,

00:07:15.460 and then exogenous molecules. Those are the five things that, as far as I can tell,

00:07:20.260 mostly you can manipulate and they can both impact your lifespan and your healthspan.

00:07:25.200 Four of those are kind of behavioral. The medications aren't really behavioral in the

00:07:28.440 sense that compliance is relatively straightforward. The other ones really require a shift in

00:07:32.540 behavior and in mindset. Maybe we all have our biases in our blind spots, but I just think

00:07:37.300 exercise is in a league of its own in terms of its potential, both on the lifespan axis, you know,

00:07:42.320 its ability to extend life and reduce all-cause mortality is well-documented. We'll talk about that.

00:07:47.280 But also on the healthspan side, it really has no rival. So it's for that reason, I think,

00:07:52.500 that we spend a lot of time inside our practice focusing on exercise. It is really the biggest

00:07:58.520 pillar within what we do because it has the most impact. And unfortunately, or fortunately,

00:08:03.780 it's also the most challenging one, I think, to get people to change their existing behaviors around

00:08:09.420 because the time commitment is significant. So let's start with some of the basics just for folks who

00:08:14.920 maybe aren't completely up to speed. What would you say if you're at a party and somebody came up to

00:08:19.480 you and said, Mike, I understand you're really into this exercise thing. Can you explain to me

00:08:23.240 why it is that exercise helps you live longer?

00:08:27.220 I think there's a couple of things, Peter, and it's multifactorial. But the first thing is that

00:08:31.500 the risk factors that contribute to cardiovascular disease, all-cause mortality,

00:08:36.320 are all influenced by exercise and physical activity. These would be blood pressure,

00:08:41.140 diabetes, to some extent, lipids and cholesterol, and also how you deal with stress. So I think you

00:08:47.060 get the big three there. There are some other new age or second wave risk factors like endothelial

00:08:52.920 function, the lining of the blood vessels in your body that improve with exercise, the way what's

00:08:58.600 called your autonomic nervous system. And people may have heard of vagal tone or heart rate variability.

00:09:03.460 That's also influenced positively by exercise. So I think there's five or six things. But what's

00:09:09.020 interesting is when you add up each one, a modest increase in cholesterol, a modest reduction in

00:09:15.120 blood pressure, those sorts of things, when you add them up, you get X percent improvement in health,

00:09:20.900 span, life expectancy, any metric you want to use. But when you look at the epidemiology,

00:09:25.660 people who do the sorts of things you just mentioned have a much bigger benefit than just

00:09:30.180 the simple sum of the other risk factors. So there does seem to be some sort of synergy here

00:09:34.800 or some sort of X factor that we don't really understand yet. But again, this collection of

00:09:40.360 lifestyle related factors, and again, the autonomic nervous system, blood pressure, lipids,

00:09:47.800 the lining of the blood vessels, and diabetes would be the big five.

00:09:51.340 I want to dive into a couple of these in depth. You know, you've thought a lot and you've looked a lot

00:09:55.120 at this literature. And one can say, look, the epidemiology is so overwhelming. The hazard ratios

00:10:00.320 are sort of absurd. When we're used to looking at a field like nutrition and looking at the hazard

00:10:05.900 ratios in nutrition, they're very small. In fact, they're so small and also so inconsistent that it

00:10:13.160 becomes almost impossible to assign a mortality benefit or addition to almost anything you can eat.

00:10:21.200 I mean, literally, jelly beans to bacon to kale. The hazard ratios are trivial and they flip-flop

00:10:29.220 from month to month. Yeah, let me tell you something that's really interesting. It's good

00:10:32.700 you brought this up. So I'm working on a review article on related topics. And one of the things

00:10:37.060 I'm looking at is all of what you might describe as natural experiments, where you have two groups

00:10:43.400 of people that are otherwise similar exposed to different things. And that's a long-use tool in

00:10:48.840 epidemiology. And people are now using it in economics and behavioral sciences. And in fact,

00:10:53.600 these natural experiments, the economists just got a Nobel Prize for them a couple of years ago.

00:10:58.380 But the classic one is the London bus driver bus conductor story led by Jeremy Morris after World

00:11:05.600 War II, where they showed the physically active conductors who are walking up and down the buses

00:11:10.640 all day had much lower rates of cardiovascular disease than the sedentary bus drivers. And it was

00:11:16.660 about 50%. And they had similar things with telephone operators versus people who were out walking around

00:11:21.960 doing things. And you look at that 50%. It's incredibly consistent. Studies of longshoremen, studies of

00:11:30.700 Harvard alumni. There's one in the last 10 or 15 years of 50,000 male and 25,000 female finishers of the

00:11:39.040 Vasa Lopet 90-kilometer cross-country ski race in Sweden. And they compared them to match controls from the

00:11:46.140 Swedish record system. And they showed, again, about a 50% reduction in cardiovascular and all-cause

00:11:51.920 mortality. There's data from the National Cancer Institute showing the same sorts of things and

00:11:57.720 showing, you know, four or five or six-year increase in life expectancy, you know, among the people who

00:12:03.700 got a substantial amount of physical activity or structured exercise, either one.

00:12:08.300 The sort of take-home point for the listener is unlike nutritional epidemiology where the risk

00:12:16.980 increases and risk reductions are very, very small and they're never consistent. I mean, there's some

00:12:22.900 things that are consistent and consistently small. For example, vegetarians consistently have a small

00:12:29.760 reduction in mortality, which of course then gets to the next point, which is what are the confounders?

00:12:34.320 And this is where I want to kind of talk about it with exercise. And this is where the

00:12:37.860 natural experiments are much better on the exercise front than they are on the nutrition front.

00:12:42.460 You see, going back to the example you gave, which is a very famous one, guys running up and down the

00:12:46.600 buses, the sort of conductor guys versus the drivers, that's a great natural experiment because

00:12:52.320 it's really not amenable to a choice. You would be less likely to believe that the bus driver who sits

00:12:59.740 there is also making poor choices relative to the other guy when he's not at work. In other words, we

00:13:06.980 wouldn't really have a reason to believe that he's more likely to be a smoker. He's more likely to,

00:13:11.580 you know, make poor food choices, et cetera. Whereas when you look at sort of the vegetarian

00:13:15.920 to non-vegetarian dietary pattern in nutrition, it's pretty clear that a vegetarian diet is very

00:13:21.540 restrictive diet. And therefore the person who's making that choice is likely very health conscious

00:13:26.300 in a number of other ways, some of which are easy to- Yeah, they have a suite of behaviors.

00:13:30.820 Yeah, exactly. Some of which are easy to measure and correct for like smoking, but many of which are not.

00:13:35.040 That's what sort of makes the nutritional thing harder. The exercise thing is pretty profound.

00:13:39.700 So let's explain to people what it means when you have a hazard ratio of 0.5, which means a 50%

00:13:48.200 reduction in all-cause mortality. What's the timeframe that that's usually looking at and how

00:13:52.580 does that translate to a five-year increase in life expectancy? The way you would say it is

00:13:58.340 the relative risk of dying of heart disease in any given period of time, whether it's a year,

00:14:03.700 five years, 10 years, whatever the study is doing is 50% lower. But now obviously not everybody dies

00:14:09.540 of cardiovascular disease. People die of other things. And so then you have to translate that

00:14:14.080 into sort of years of life gained. And typically the years of life gained are somewhere on the order

00:14:20.580 if you account for smoking of three to five years, something like that. And then if you look at the

00:14:26.520 concept of health span, you may get six or eight years of improved health span.

00:14:31.340 So health span is, you know, Peter, how disability-free you are. And so you have, you know,

00:14:37.060 four or five-year increase in life expectancy and a four or five-year additional increase in health

00:14:41.520 span. And the idea, you know, is to live a long time and then die quickly with minimal disability.

00:14:47.980 That's right. And I've always found that the current medical definition of health span,

00:14:52.300 I understand why it exists because you have to be able to quantify things, but I've also found it

00:14:56.320 to be not entirely helpful. You know, freedom from disease and disability, which is the current

00:15:00.340 definition, I think that's a pretty low bar. One of the ways we try to get around this idea of the

00:15:06.220 vagueness of freedom from disease and disability is to make it very, very granular. And we do this by

00:15:12.460 creating this model we have called the centenarian decathlon, which says, if you go out to your

00:15:18.120 marginal decade, and we define the marginal decade as the last decade of your life. So again,

00:15:22.060 we don't know when that is, but let's just make the math easy and say, oh, that's going to be 79 to

00:15:26.100 89 or 81 to 91. You're in your marginal decade. What are the athletic events and the activities of

00:15:34.680 daily living that you want to be able to do? But we do it by making people cross off things they do

00:15:41.180 not want to do. So we make this a, you have to opt out of things. And they're very specific. So it's

00:15:48.100 like walking three miles in one hour, being able to climb X number of stairs, you know, 60 stairs

00:15:56.260 that are eight inches in one minute, being able to carry 20 pounds of groceries, a certain distance,

00:16:03.920 being able to get up off the floor with at most one hand of support. So it's very specific stuff.

00:16:11.420 And I think for most people, the initial reaction is, well, that's really easy. Like I can do most of

00:16:17.700 these things today. But when you're a 45 year old reading that, I hope that's easy. I don't think

00:16:22.180 they appreciate the precipitous decline that will occur without deliberate training. And it's for

00:16:28.420 that reason that I think exercise has more potential to offset all of those things than anything else,

00:16:34.760 sleep, nutrition, certainly any medication. To me, that's really what healthspan comes down to.

00:16:40.900 It's not just, I'm not disabled, but it's, I'm really thriving.

00:16:44.860 Yeah, I'm engaged. I can engage in what I want to engage in. I think, Peter, you've hit the nail

00:16:49.920 on the head. What we see in those decades, what's really instructive is if you look at

00:16:55.800 the decline in performance in age group, swimming, running, cycling, rowing, any sport where there's

00:17:02.200 pretty good record keeping, is people can start to decline at age 30 without training. You can push

00:17:08.720 that back to age 40 with training. In other words, if you work out every day and relatively hard.

00:17:13.220 But then something happens to people in their middle 70s where there seems to be a steeper

00:17:18.740 rise. And what's interesting about that steeper rise is it seems to shift from sort of a cardiopulmonary

00:17:25.000 limitation to sort of a skeletal muscle strength slash frailty situation. And what you described in

00:17:31.680 terms of getting up off the floor, 70% of 70-year-olds can't get off the floor. Not one hand, two hands,

00:17:37.460 just can't get off the floor. And we both know from being doctors, if you look at what happens when a

00:17:42.340 person in that age group falls, it's just no fun. So if you look at what really takes people out,

00:17:48.000 it's things like falls, it's inability to do things. And so what happens is walking three miles

00:17:53.940 in an hour takes some cardiopulmonary capability, but not a ton, just some. Whereas being able to go

00:18:00.880 up the stairs takes more, being able to get off the floor takes more. One of the things that people

00:18:05.680 have to think about, especially as they get into their forties and fifties is adding strength or

00:18:10.460 some sort of circuit training and agility training to their program. And one of the things I do is

00:18:15.680 I'm 63, almost 64, is I have the jump rope my mother gave to me when I was 14. She gave me a

00:18:22.060 beautiful boxer's jump rope, leather with ball bearings in the works. I carry it with me when I

00:18:28.280 travel because you can always jump rope, even if it's out in the parking lot of a hotel. People think

00:18:32.960 they're nuts, but it's a terrific exercise. It actually is for a number of reasons, including

00:18:38.240 foot reactivity. You know, the lack of foot reactivity is something that can contribute to

00:18:42.400 the fall. So you're getting the cardio benefit, the coordination benefit, and also this gentle foot

00:18:48.060 reactivity without, and it depends if you know how to skip like a boxer, you don't have to really

00:18:51.560 pound your knees as well. And the other thing is you do that with some body weight, things as simple

00:18:56.560 as pushups or planks, and there's a place to do some pull-ups, you're good to go. There's so many

00:19:01.800 things you said there, Mike, that I want to go back on and just make sure people really capture,

00:19:05.160 because it's so important. We'll probably find this study and I'll link to it, but there's an

00:19:08.480 amazing study that demonstrates like muscle mass changes, strength changes, and activity changes in

00:19:14.680 men and women as they age. And it's one of those things where you don't actually need to understand

00:19:19.540 the statistics to be able to see the figure. And it's exactly as you describe it. At the age of 75,

00:19:25.760 there is a cliff that is so violent, you can't believe what you're watching. It's at that cliff

00:19:34.120 where physical activity level declines like this. It just goes boom. Muscle mass goes boom. Strength

00:19:43.480 boom. Same thing. Of course, it begs the age-old question, is the patient losing strength because

00:19:49.880 they are no longer active or are they no longer active because they have lost strength? My view is it's

00:19:55.080 both. I think these things feed off each other. Which one's the first insult? I suspect it's

00:20:00.440 probably the loss of strength that contributes to the loss of activity. But then I think those

00:20:04.820 feed back and accelerates this thing. You really get into a death spiral. That's why it becomes

00:20:11.540 important to keep exercising relatively hard as you get over at least a few days a week to slow this

00:20:17.480 decline. And there are remarkable examples. There are some Swedish cross-country skiers, men who were

00:20:23.740 world and Olympic champions in the 40s and 50s. Many of them were woodsmen and lived in the countryside,

00:20:30.460 remained very active skiing and so forth. They were studied in their 80s. Now, you could argue that

00:20:35.360 there was something special about these guys to begin with or they would not have become champion

00:20:39.500 athletes. But their rates of decline were quite modest. And more importantly, their fitness levels

00:20:45.760 were similar to what you would see in people in very early middle age. The other interesting thing

00:20:50.600 about that is the classic studies from the 1960s. These fighter pilots, Navy and Marine and Air Force

00:20:56.980 fighter pilots were sent into outer space. These were incredibly fit guys. They'd go for a week and come

00:21:02.560 back completely atrophied, couldn't stand up, and really in bad shape. And in 66, NASA commissioned folks

00:21:09.380 at the University of Texas Southwestern Medical Center in Dallas to put five college-age males, two athletes,

00:21:14.920 at bed rest. And they had tremendous reductions in their fitness over just three weeks of bed rest.

00:21:21.380 And interestingly, Ben Levine and his group in Dallas alone with the late Jerry Mitchell brought

00:21:25.420 these same men back 30 years later. So now they were early 50s. And it's incredible, but three weeks of

00:21:32.840 bed rest caused losses of physiological function associated with 30 years of aging.

00:21:38.560 Wow. So it's an incredible study. And that's one of the things that is instructive. Those sorts of

00:21:44.740 small studies. And that's why it's so important to just avoid inactivity of any type. And whether

00:21:50.080 it's low-grade physical activity, whether it's walking the dog, whether it's gardening, whether it's

00:21:54.720 taking a flight of stairs once in a while, or intentional working out, it's really the way to go.

00:21:59.240 And as you point out, really, in those lifestyle factors you mentioned, really sort of overwhelms

00:22:04.380 things. Overwhelms almost everything else. You mentioned and alluded to the danger of a fall

00:22:10.920 in later life. And this is something we've been doing a lot of research on internally,

00:22:15.820 given our concern around bone mineral density in the aging population. The mortality, when you look

00:22:22.300 at 65-year-olds and up who suffer a fall that results in the fracture of any part of the hip or

00:22:29.380 femur at one year, depending on the study, it can be as low as 25%, as high as 60%.

00:22:37.680 Yeah. The magic number is usually around 40, 50.

00:22:40.500 Yeah. I want people to understand what we just said. You take all the 65-year-olds and you look 0.73

00:22:47.140 at those who fall and the fall results in a broken hip or femur. And you ask the question,

00:22:53.080 how many of those people will be alive in 12 months? The answer is half of them.

00:22:56.920 And the other half, it's not like the other half are-

00:22:59.260 They're not back to themselves necessarily.

00:23:00.600 No, exactly. You want to avoid a major health like that for sure. And the other thing, Peter,

00:23:05.980 there's a couple other things that have really hit me as we've talked. One is this man named

00:23:10.500 Lester Breslow, who was this very famous epidemiologist who died in his late 90s,

00:23:16.460 was at UCLA for many years. And he studied people in Oakland in the late 50s and early 60s who made it

00:23:22.480 to 90. And the sorts of four or five things you talked about, he identified the people in Oakland

00:23:28.580 who made it to 90. And they were non-smokers. They weren't obese. They remained physically active.

00:23:33.220 They ate modestly. They stayed engaged in life. And there was just five or six things that they did.

00:23:38.620 And the same is true in the Honolulu Heart Project, when they've looked at a huge number

00:23:42.000 of Japanese-American males, same exact stuff that you mentioned. They weren't as focused on the small

00:23:47.560 molecules, but exactly what you've described. And then I think about natural experiments.

00:23:53.080 At the Cooper Clinic, they've looked at people's fitness levels. Now, that's not exactly the same

00:23:57.700 as physical activity. But in general, the fittest people are also the most active.

00:24:02.220 And they divided people into three or four groups of fitness and then had them look at a so-called

00:24:07.600 healthy eating index. Were you a junk food junkie? Did you eat okay? Or were you really conscious of

00:24:13.100 your diet? The healthy eating index in people that weren't particularly fit did have something to do

00:24:19.140 with all-cause mortality. But among the fittest people, there was very little impact of diet

00:24:24.720 on the outcomes, which is sort of interesting. It always brings me back to the famous quote in a

00:24:29.740 book about distance running called Once a Runner, where somebody said, if the furnace is hot enough,

00:24:34.360 you can burn anything, even Big Macs. Now, you have to take that with a grain of salt,

00:24:38.580 but it does kind of give you the take-home message. But just about what a powerful thing

00:24:43.700 exercise is. There's a very common mantra that says, oh, you can't outrun a bad diet. And I would

00:24:49.520 argue that's probably not true. I think you can outrun a bad diet, but it's pretty hard to do. And

00:24:54.200 most people don't understand the amount of running that's needed to do it. There's this incredible

00:24:58.120 study from the 50s, people who worked at a jute plant in India, and they categorized people on

00:25:04.420 incredibly physically active, doing manual labor, hacking away on jute to make, I think, linen or

00:25:10.380 rope. They were going to make rope with this stuff, all the way to office workers. As you got more and

00:25:15.660 more physically active, people got lighter. As you got more inactive, they got heavier. But what was

00:25:20.740 interesting is people that were in the middle rung of occupational physical activity also had

00:25:27.540 slightly lower caloric consumption, remained very trim. If people are physically active enough,

00:25:32.280 if you read the old papers about what lumberjacks were eating when they were chopping wood all day

00:25:38.160 long, I mean, it's 5,000, 6,000 calories a day. The old order Amish who walk around and do manual 1.00

00:25:44.400 labor all day long and don't have tractors and stuff like that, they eat an awfully lot and very

00:25:48.600 few of them are obese. You can't outrun a bad diet or can't out exercise a bad diet in a modern high

00:25:56.640 calorie, low physical activity world, I think is the caveat that has to go to that one.

00:26:01.020 And yet, when you look at athletes that are doing insane amounts of exercise,

00:26:05.900 most of them have a hard time keeping on weight.

00:26:08.600 Yeah, there's a terrific study about the Tour de France where they get done every day and they're

00:26:12.060 just handing them food. And these people are eating ad lib, except when they're on the bike and even

00:26:17.100 when they are on the bike. And they have a hard time and they're eating 6,000 calories a day,

00:26:21.280 they weigh about 150 pounds. And they have a hard time keeping their weight.

00:26:24.760 They are catabolic throughout the tour. I mean, they finish in pretty bad shape.

00:26:28.120 Correct. They look like not death camp survivors, but people who certainly haven't had a lot to eat

00:26:32.900 for a few weeks.

00:26:34.000 So let's go back to something you said at the outset, which was the impact of exercise on the

00:26:39.000 autonomic nervous system. Explain to folks what the autonomic nervous system is, how it differs from

00:26:44.820 the sympathetic nervous system, and why it plays such an important role in our health. And of course,

00:26:50.000 how exercise impacts it.

00:26:51.200 When we think about the nervous system, normally we think about our brain, our eyes, our ears,

00:26:56.240 and our senses, and also our ability to grab things, move our muscles, that sort of thing,

00:27:00.420 feel pain or feel heat or cold or sense the environment. But your autonomic nervous system

00:27:05.420 is what controls your internal environment. And it's called homeostasis. So, you know,

00:27:11.280 we can increase our metabolism 10 or 20-fold with exercise. Our body temperature only rises a degree

00:27:16.840 or two. And so this happens due to the actions of the autonomic nervous system. Now, there are two

00:27:22.620 branches of the autonomic nervous system. There's the sympathetic nerves and the parasympathetic

00:27:27.840 nerves. And these used to be kind of categorized as fight or flight. You would either activate,

00:27:34.720 especially the sympathetic nerves, if you needed to fight or fly, run away. And whereas the

00:27:40.400 parasympathetic nerves were seen as what happened when you were asleep, when you're digesting your food,

00:27:46.080 so on and so forth. But it turns out there's kind of more of a balance and a yin and a yang between

00:27:50.780 the two that happen all the time. But the parasympathetic nerves, and the most notable

00:27:55.680 one is the vagus. They control part of your heart rate, make your heart rate slower. They also tend to

00:28:01.260 lower blood pressure, and they're critical to digest your food. That's one side. The other side is the

00:28:06.780 autonomic nervous system. Nerves that increase your heart rate, stimulate your blood vessels to constrict,

00:28:12.780 help your muscles contract harder, and also do things like make you sweat. And the key thing

00:28:19.480 to remember is that they help you regulate the internal environment, and that exercise really

00:28:24.480 keeps these things tuned up. And by having your autonomic nervous system a bit better tuned up,

00:28:30.020 it can do a better job regulating your internal environment. The classic example being your blood

00:28:35.480 pressure. Now, of course, what everybody knows, and we're going to talk in a moment about VO2 max

00:28:40.680 testing and how that's done, because I want to get into the weeds on that. But when we have our

00:28:44.380 patients tested, we have a protocol. We look at their blood pressure before, and then we look at

00:28:49.400 their blood pressure throughout. And then we want to look where they are percentile-wise at the max

00:28:54.160 exertion, what's their blood pressure. And without exception, a person's blood pressure goes up when we

00:28:59.200 do a VO2 max test. So you take somebody whose blood pressure is 115 over 75 at the outset, they'll easily be

00:29:04.780 160 over 95 or 100. And that's completely normal and healthy at a max.

00:29:11.000 Even higher if you measured it while they're weightlifting.

00:29:13.300 So explain to folks why it is that during exercise, nothing looks good, right? Blood pressure is high,

00:29:21.480 heart rate's high, heart rate variability is low. What is it about the recovery phase from exercise

00:29:28.300 that produces a net positive effect, even though in the moment exercise presumably is doing things

00:29:35.400 that are not necessarily in our body's best interest in that moment?

00:29:38.840 I would say they are in their best interest because what happens is the system shifts a little bit to

00:29:44.200 kind of meet the demands of the skeletal muscle. You got to be able to contract the muscles to exercise.

00:29:50.560 And again, that's sort of consistent with the fight or flight thing. If you're going to run away or be in a

00:29:54.360 fight, you want to be able to contract your muscles. And so to do that, you need to send more blood flow

00:30:00.160 to those muscles. And one of the ways you do that is by increasing your blood pressure. More blood

00:30:04.880 pressure equals more flow. And the other thing you got to do is increase the pumping function of your

00:30:09.700 heart. At rest, people's heart is beating about five liters or a little over a gallon a minute.

00:30:15.760 During moderate exercise, it can be 10 liters a minute. During heavy exercise, 15 or 20. And elite

00:30:22.160 athletes who are very trained and have very large hearts, it can be 30 or 40 liters a minute.

00:30:26.780 So what happens is you're pumping all that blood out against these blood vessels and so your blood

00:30:31.320 pressure rises. So it's a completely normal thing to generate that large cardiac output. Cardiac output

00:30:38.400 is heart rate times stroke volume. That's the amount with each squeeze of the heart. And so naturally,

00:30:43.440 you're going to want to increase your heart rate. So that's what happens. But then when you stop,

00:30:47.540 as you mentioned, heart rate falls, blood pressure falls, and things look probably better than they

00:30:52.920 did it in somebody who is untrained and hasn't exercised. What do we know about the rate of

00:30:58.300 recovery? There's something called heart rate recovery, HRR, that is a pretty interesting metric.

00:31:04.620 Tell us what we know about HRR. So people do a maximum exercise test and their heart rate's,

00:31:09.880 you know, 150, 160, 180, whatever their age is. And 220 minus your age is an interesting number,

00:31:15.540 but there's a lot of patient to patient or person to person variability. So what happens is how fast

00:31:21.140 does your heart rate go back down to some number? How fast does it get until it's under 100? How fast

00:31:26.960 until it goes back to baseline? Whatever. So the faster it goes down, the faster it goes down,

00:31:33.140 the better the action of your vagal nerve, the nerve that slows your heart rate. The vagus nerve is also

00:31:39.360 responsible mostly for your heart rate variability. And this nerve also suppresses funny heartbeats and

00:31:46.280 is protective when it's in good shape against arrhythmias and ventricular tachycardia, ventricular

00:31:51.960 fibrillation, sudden death, all of those things. And so heart rate recovery, heart rate variability,

00:31:58.640 all of those things are indirect markers of what we call vagal tone or vagal activity. And that's a good

00:32:05.740 thing. Now heart rate variability can be quite genetic, right, Mike? The absolute number in

00:32:10.700 milliseconds between any two individuals can be quite distinct. And it seems to be not nearly as

00:32:16.800 modifiable as some other factors. Have you found that to be the case? Again, it depends on what sorts

00:32:22.180 of training people have been doing, what they've been exposed to. But in general, you know, most people

00:32:27.060 can get a nice training bradycardia, which again is vagal tone. And most people, if they're trained,

00:32:32.520 can go from, you know, slow heart recovery to faster heart rate recovery and also have more

00:32:38.320 heart rate variability. So I think worrying about the differences in the initial baseline, Peter,

00:32:42.780 while interesting and what they might be attributable to is probably less important than the fact that

00:32:47.860 they're modifiable, as you mentioned, you know, as they say at the top of the show.

00:32:52.300 So let's talk about this VO2 max test because we're going to talk about what it means and how

00:32:56.260 predictive it might be of an individual's mortality. So let's just start by explaining to people what

00:33:03.160 you do when a person comes into the lab. So what you do is you get them on a bike or a treadmill,

00:33:10.320 you put some EKG electrodes on them, and they either run on the treadmill or ride a bike and they have a

00:33:16.180 nose clip on if you're going to measure it directly and either a face mask or a mouthpiece that they

00:33:21.320 breathe. And that allows us to measure how much air they breathe in, how much air they breathe out.

00:33:27.760 We know that the air has 21% oxygen coming in. If we measure the amount of oxygen in the expired air,

00:33:33.260 we can make an estimate of how much oxygen has been consumed. And so what happens is when people start

00:33:40.260 to exercise, they go from using about three and a half mLs per kg per minute, or maybe 250 mLs or 300 mLs,

00:33:50.160 like 10 or 12 oz of oxygen per minute. And an unfit person in their 30s or 40s can typically increase

00:33:57.740 that about 8 or 10 fold to say 30 or 35 or about 3 liters a minute. And with training, most people

00:34:06.520 can increase things at least 10 or 20%. And if you have some ability and or you train very hard,

00:34:12.700 some people can almost double it. So what happens is once your VO2 max goes up, again, just like

00:34:19.940 physical activity. It's a measure of physical fitness, and it's also linked to all-cause mortality.

00:34:26.640 So the fitter you are, the lower your chance of dying in the next year, two years, five years,

00:34:31.740 10 years. For many years, they thought that things sort of plateaued at what they call about 10 or 12

00:34:37.440 METs. A MET mean your resting metabolic rate. So you had to be able to get 10 METs. And 10 METs is

00:34:43.120 being able to run one mile in about 10 minutes, roughly, for the average person. Henry Ford and

00:34:49.240 Detroit have shown that that continues to rise even up to 15, 16 METs. So people that are quite fit

00:34:54.920 continue to gain benefit in terms of all-cause mortality. I mentioned the cross-country skiers

00:35:00.880 earlier. And while they didn't do VO2 max tests in those people, the people who had completed the most

00:35:06.240 races and done the races the fastest, so people who had both been active for the longest period of time

00:35:12.120 and probably were the fittest, also had lower all-cause mortality. Not compared to sedentary

00:35:17.500 periods, but compared to people who'd done a few races a little bit slower. So yeah, peak fitness

00:35:22.640 matters. There's a paper in JAMA that I think is by far the most compelling description of this

00:35:27.380 phenomenon. A couple things are noteworthy about it. I've talked about this on a previous AMA.

00:35:32.200 I would consider it one of the 10 most influential papers that I have read in terms of changing how I

00:35:38.060 think about healthspan and lifespan. As you said, the relationship is monotonic and it does not

00:35:45.100 plateau. That's an important thing to appreciate, which is this is a more is better phenomenon. And

00:35:52.140 very few things in physiology are more is better. Usually physiology behaves in U's and upside-down U's 0.65

00:36:00.360 or maybe J's and things like that or plateaus, sigmoid curves. But this is not the case here.

00:36:06.400 This study that we're talking about put people into the bottom 25th percentile, 25th to 50th percentile,

00:36:12.900 50th to 75th. And then the last group, it basically divided into 75th to 97 and a half. And then they had

00:36:19.420 that little sliver of people that they called elite that were at the top two and a half percentile.

00:36:24.800 And all-cause mortality just went lower and lower and lower and lower. And if you looked at the

00:36:29.940 hazard ratio the other way, because we often think about hazard ratios and risk reduction,

00:36:33.140 but if you look about it in risk increase, when you compared the people in the top two and a half

00:36:38.720 percent, the VO2 max to the bottom 25 percent, the hazard ratio moving in that direction was 5.04,

00:36:46.680 if my memory serves me correctly. That means there's a five-fold increase in all-cause mortality

00:36:52.820 between the fittest two and a half percent and the least fit 25 percent. And even when you took

00:36:59.040 something less extreme, I believe if you looked at the least fit 25 percent to the third quartile,

00:37:06.060 so the 50th to the 75th percentile, the hazard ratio was still about just below three. I think

00:37:11.700 it was 2.75-ish, which was kind of right on par with the increase in mortality that you would see

00:37:18.900 from having end-stage renal disease, which is, by the way, greater than the hazard ratio associated

00:37:23.840 with smoking. Being unfit is an incredible risk factor. And people like Frank Booth have argued

00:37:30.180 that it should be, for lack of a better word, the risk factor. And Jill Barnes, one of my fellows at

00:37:36.020 the time, she's now at the University of Wisconsin, a faculty member. She and I wrote an editorial for

00:37:40.840 Mayo Clinic Proceedings maybe 5, 10 years ago where we said, look, if people had 12, 13, 14 met peak

00:37:48.680 exercise capacity, other than doing cancer screening, you could probably just ignore everything else.

00:37:55.760 I don't think anybody's ready to go there, the sorts of people who do health screening and that

00:37:59.380 sort of thing. But if you screen people for physical fitness and, again, just did the routine kind of

00:38:04.400 cancer screening, and you can even argue that you could probably cut back on the routine cancer

00:38:08.760 screening for most things, except skin cancers, because fit people tend to be outside of it more.

00:38:14.020 You can make that argument. And you can make it with a straight face, and the data's there to support it.

00:38:18.020 And I would belt and suspenders it and say, but look, I'd still do the cancer screening. I'd still

00:38:22.480 consider aggressive lipid management and things like that. But you're absolutely right. I mean,

00:38:26.320 there's really no intervention that we have that's going to rival it.

00:38:29.820 I think you mentioned lipids. I think there's a couple of things you got to remember. One,

00:38:34.620 especially for people who pick it up late in life, exercise is not a vaccine. And one of the most

00:38:40.320 incredible studies ever done, again, we're talking about in a one experiment of nature sorts of things.

00:38:44.820 There was a man named Clarence DeMar. He won the Boston Marathon seven times.

00:38:49.280 Born, I think, in 1888 or 1890. Also won a medal in the 24 Olympics, got a bronze medal in the marathon.

00:38:56.060 And he really is almost like master athlete number one. So he kept training his whole life.

00:39:01.360 Ended up dying, I think, of stomach cancer at about age 70. So he didn't live to be a gazillion.

00:39:07.160 But remember, he was born in 1888 or 1890. Paul Dudley White, a famous cardiologist,

00:39:12.620 we know him from something called the Wolf-Parkinson-White syndrome, a weird kind of

00:39:16.060 funny heart people get. He did an autopsy on DeMar. And he'd run really until very late in life.

00:39:21.780 And he had some plaque or fatty builds up and calcium buildup in his coronary arteries.

00:39:28.200 But his coronary arteries were huge, were just massive. And subsequent to that,

00:39:34.040 a man named Bill Haskell out at Stanford in the middle 90s, studied a bunch of people who've

00:39:39.120 done ultramarathons. And they did the same thing, except this time they put catheters in and

00:39:43.420 injected drugs to make the blood vessels expand. And they showed the blood vessels were bigger and

00:39:48.180 they expanded more. So again, while you could still have some blockages, even if you exercise,

00:39:54.000 and there are people with horrible lipids who do, in fact, get heart disease in spite of exercise.

00:39:58.940 So it's not a complete vaccine. Its overall protective effect is quite large, both in terms of

00:40:05.240 what it does to people's lipids, but the fact that the blood vessels get so much bigger

00:40:09.120 and the linings of the blood vessels are healthier.

00:40:12.380 Mike, one of the things that we've looked at a lot internally is the literature that argues a

00:40:17.860 different point. The literature that argues that, in fact, there's a J curve here. And we all agree

00:40:23.660 that a person who doesn't do anything is at the highest risk. The literature is so unambiguous there,

00:40:30.020 it doesn't warrant any further discussion. But let's now look at the addition of work. Now,

00:40:35.680 I just want to make sure the listener understands the way we're going to talk about this. Let's

00:40:38.640 talk about these in met hours per week.

00:40:40.380 A weird metric for sure.

00:40:42.200 I've actually had to convert my own training into a met hour per week spreadsheet so that I can

00:40:47.820 interpret what I do in the context of all the literature. Totally weird. But let's explain to

00:40:52.020 people what it is. So you told us what a met is. One met is the metabolic expenditure of sitting

00:40:56.800 at rest, which corresponds to about 3.5 milliliters per minute per kilogram of minute ventilation,

00:41:03.320 or actually VO2. So oxygen ventilation, not full minute ventilation. Then let's talk about how that

00:41:08.080 ramps up. How many met is it, Mike, to walk three miles in an hour?

00:41:12.120 Probably four, five, six, something like that. I don't know.

00:41:14.800 Oh, is it that high? Okay. I would have guessed lower.

00:41:16.960 It may be because remember a 10 minute mile is 10 met.

00:41:21.040 10 minute mile is six miles in an hour. And that's pretty nonlinear. Yeah, you're right. It's

00:41:25.640 probably about three to four met, I would guess. And then of course, as you noted, to run six

00:41:30.260 miles in an hour would be 10 met. So let's say you did that. You ran six miles in an hour for an

00:41:36.440 energy expenditure of 10 met. So that would be 10 met hours. You did 10 met times one hour. And if

00:41:42.120 you did that four times a week, and that was the only thing you did, you'd be at 40 met hours per

00:41:47.300 week of activity. So I do this for my training. I spend how much time am I on the bike at this

00:41:52.420 many watts, at this many watts, and in the weight room and carrying my rucksack. And I'm sort of in

00:41:57.860 the 100 met hours per week category. So if you look at the literature, the epidemiology on this,

00:42:03.800 it would say my mortality risk might be higher. That would be the headline than someone who's

00:42:10.000 doing 40 met hours per week. In other words, it's a J curve. So it sort of starts up here, 0.52

00:42:15.920 highest mortality at nothing. Mortality comes down, sort of naders, depending on the study,

00:42:20.860 between 50 and 75 met hours per week. And then the mortality tends to climb. Now,

00:42:25.800 I won't go into this in great detail other than we've looked at every one of these papers and we

00:42:30.140 find significant fault in each of them. What do you see? Not all of them say that in the sense that

00:42:35.880 some... That's right. Some of them don't. The big NCI study with 650,000 patients or subjects didn't say

00:42:42.180 that. And again, what I really like is that cross-country ski paper that I mentioned from Scandinavia.

00:42:47.820 If somebody's going to ski 90 kilometers and if they're going to do it year after year and they're

00:42:52.320 going to do it fast... They have to be training a lot.

00:42:55.080 You're going to have to be training a lot. You're going to have to be training year-round. You almost

00:42:58.020 are certainly getting all sorts of met hours and training pretty hard. Now, the one caveat in all

00:43:03.920 this, and I agree with you completely, I don't think the evidence for a J curve is particularly good.

00:43:09.620 The other thing is in many of these studies, the number of people that are way out there is very

00:43:14.040 small. So, even one death, somebody gets hit by a car or something, it can make a difference. That's

00:43:18.860 certainly one of the problems with a study from Copenhagen, as I recall, or Norway, but one of

00:43:23.400 the Scandinavian capitals. So, I really think that the dispositive study here is the real-world data

00:43:29.060 from the Vassalopet story. Now, the one thing that does happen is people do have an apparent increase

00:43:34.980 in risk of atrial fibrillation. A couple of caveats to that. The first thing is they do not have

00:43:40.340 any increased risk of fatal arrhythmias. Atrial fib is no fun, but it certainly can lead to medical

00:43:47.120 problems, but not typically to kill you. The sorts of things that kill you, ventricular arrhythmias,

00:43:52.720 these are not seen to any greater extent in these people that are really heavy exercises for their

00:43:57.180 entire life. So, then the question becomes, do these people actually have more atrial fibrillation,

00:44:02.440 or is it just that they're exercising and notice it? And that's the controversy. I think you would

00:44:07.300 probably have to say that people who train what you're talking about for their entire life have

00:44:13.220 some increased risk of atrial fib compared to people that are just super healthy otherwise,

00:44:18.980 physically active at that 50 to 70 met hour per week thing you're talking about or level you're

00:44:23.200 talking about. But your risk of atrial fibrillation is still probably lower than people who are sedentary,

00:44:28.540 hypertensive, obese, diabetic, and so forth. And there are good treatments for atrial fibrillation,

00:44:33.580 and you're continuing to be protected against fatal arrhythmias.

00:44:37.140 And what do you think about sort of myocardial fibrosis? There's been some talk about that.

00:44:41.240 Do we see compelling evidence to suggest?

00:44:43.620 Again, the data from Ben Levine's group down in Dallas, where they've done a bunch of echoes and

00:44:47.640 loaded the heart and done all kinds of things. And they show that fit young people have very flexible,

00:44:54.300 compliant heart muscles. And they show that that declines with age, but doesn't decline nearly so fast

00:45:00.180 in people that are either habitual exercises or people who remain master athletes or remain

00:45:04.300 highly competitive. So again, I think that you can talk yourself into these sorts of things

00:45:09.900 through a case report here, a case report there. But when you look at the sort of data that came from

00:45:14.720 Ben's lab and other things, you see that this sort of training keeps the ventricles compliant,

00:45:20.580 flexible, and able to handle the increased demands and pumping demands of exercise. So I think the

00:45:27.080 fibrosis argument's a little spurious. I think we've talked a little bit earlier about large

00:45:32.400 coronary arteries in people that are habitually physically active. We've talked that those

00:45:37.340 arteries vasodilate better. They probably are less likely to generate a clot. And then we've just

00:45:44.000 simply said, and you're protected against fatal arrhythmias, we've just simply said there may be a

00:45:47.960 subtle increased risk in atrial fibrillation. But again, good treatments for atrial fib. So I think

00:45:53.240 they're in good shape. I think in that regard, doing as much as you do, Peter. And the other

00:45:57.600 thing to remember is that it's not an absolute vaccine or an absolute, you work out an hour a day,

00:46:03.200 you're never going to get, have heart disease, but I think your risks are going to be dramatically

00:46:06.860 reduced. The other thing I think that argues against a J curve is the VO2 max data that we just

00:46:12.920 discussed, which is an enormous cohort, probably the largest cohort after the Copenhagen cohort and far

00:46:18.740 more balanced in terms of the number of people in each group. And has been repeated in other

00:46:23.100 populations. So there you have to ask the question, how is it that people in the top 2.3%

00:46:29.640 of the population for VO2 max have the lowest mortality by a long shot if they're not training

00:46:36.820 significantly? I know those numbers very well. I mean, we put all of our patients up against that

00:46:41.720 template and we show them where they are and where we want them to be. And we actually hold them to an

00:46:45.600 even higher standard, Mike. We kind of want our patients to be at the elite level for a decade

00:46:50.940 below where they are actually are age-wise. And I'll tell you in a moment why we do that. I want

00:46:54.780 to see if you agree with my logic. I don't see how you're going to get there doing 40 mat hours per

00:46:59.300 week. You can't achieve a VO2 max of that level just doing a little bit of maintenance stuff here

00:47:05.320 and there. You have to be training. Yeah, you have to be training. You have to be doing some high

00:47:08.880 intensity training. So I agree with you. The other thing is if you look at some classic studies by

00:47:13.140 people like Bob Hickson and more recently Wissloff's group up in Norway, people who do some

00:47:18.860 longer intervals three or four times a week can get a lot of bang for their buck in terms of VO2 max.

00:47:24.740 I want to come back to that, Mike, because I want to talk very specifically about the different

00:47:28.320 modalities for training. Before I do, I want to see if you can check my logic on this. A big part of

00:47:33.940 where we come up with the reason you want to have a high VO2 max when you're young is we want to be

00:47:40.360 able to prepare for the inevitability of decline. So I want to start by just asking you, what is the

00:47:45.360 most up-to-date understanding of how much peak VO2 declines? And let's do it in a non-training

00:47:52.440 individual and a training individual. So in general, people think VO2 max declines about 10%

00:47:58.240 per decade starting in the fourth decade, so sometime in your 30s. You know, some people say 9,

00:48:03.480 some people say 12, some people say 8, but roughly 10%. A lot of that is driven by age-related decline

00:48:09.200 in heart rate. But in people that are not training, it's driven because their heart can't pump as much

00:48:14.760 blood and their muscles can't use it. So among people who are training, you start at a higher

00:48:20.120 level. And then if people continue to train, you probably don't see a big decline until your late

00:48:26.880 30s or early 40s. And we see that among athletes because there are world-class endurance athletes in

00:48:31.780 the early 40s. And then you can reduce the rate of decline by about half, certainly up to your 70s

00:48:40.740 probably. Now, not everybody keeps training hard. If people stop training, their VO2 max falls

00:48:48.180 precipitously. Dr. Dave Costell, really one of the founders of exercise physiology in the United States,

00:48:54.300 studied a lot of elite athletes in the 60s and 70s. He brought them back to his lab when these guys

00:48:59.480 in the 90s, 1990s, when they were in their late 40s and 50s. And about a third of them had continued

00:49:05.440 to train very hard and had minimal reductions in their VO2 max. A third had become sort of joggers,

00:49:10.520 had some reduction. And there was a third that had just stopped doing anything and they looked like

00:49:14.720 regular sedentary people. So you do have to stay at it. A group of master athletes out in the LA area

00:49:19.580 were studied. Same sorts of things. People declined and their VO2 max declined. But among the people who

00:49:26.400 continued to train intensely, in the case of the men do some strength training, their VO2 max declined

00:49:33.120 at a much lower rate. So you have a situation where it's 10% if you do nothing. And if you really work

00:49:39.520 at it and stay with it at a really high level, it's maybe 5% or 6% per decade. But most people

00:49:46.180 who've been super competitive can't quite keep doing that their entire life. So they drop off a little

00:49:50.740 bit. But even if they drop off 10% per decade, they start at a much higher baseline. If your baseline

00:49:56.600 is 60 versus 35 and you lose 10% per decade, you're still going to be way, way, way ahead.

00:50:02.540 And at age 60 or 70, you're going to have a VO2 max value higher than a 30-year-old.

00:50:09.460 The reason we push so hard, Mike, for our patients to have as high a VO2 max as possible when they're in

00:50:15.620 their 40s and 50s, is based on this inevitability of decline and with the hopes that we're extending

00:50:22.140 life by a decade so that, hey, even though actuarially you might only be expected to live

00:50:27.800 to 81, we're kind of hoping you're going to get to 91. And if you say you want to be active,

00:50:33.580 then we have to reverse engineer what that means. So what do you think is the VO2 max above which

00:50:41.760 you have absolutely no limitation on any normal person's activities? In other words,

00:50:48.020 if you said to me, hey, look, when I'm in my 80s, I want to be able to do pretty much anything

00:50:54.340 reasonable. I don't have to run a five-minute mile, but what I do want to be able to do is I

00:50:58.660 want to go on a hard hike. And if that means I got to climb 100 feet in half a mile, so be it.

00:51:06.060 That's a great question. It goes back to one of your earlier comments about

00:51:09.880 your scale versus the traditional kind of anti-frailty scale. And what do you want to

00:51:14.900 not be able to do when you're 85 or whatever the magic number is? A VO2 of 14, mLs per kg per minute

00:51:22.000 or four METs. Four METs is required from an oxygen consumption perspective for people to do their

00:51:28.000 activities of daily living, which means an occasional somewhat brisk walk for a few minutes and be able

00:51:34.480 to kind of get around the house, go to the supermarket and be, quote, independent, whatever that means.

00:51:38.640 If you want to be able to run a mile in 10 minutes, that would be-

00:51:43.660 35 VO2 max, yeah.

00:51:45.020 Yeah, 35 or 10 METs. So somewhere between those two are the magic number. So I would say that,

00:51:51.220 you know, if somebody in their 80s had a max in their 20s or lower 30s, that'd be terrific.

00:51:56.700 We have arrived at 30 to 31 as the magic number.

00:52:00.680 That would be a rough guess. And what's interesting that you mentioned that

00:52:03.920 is those Scandinavian elite skiers I mentioned had values in that very high 30s or low 40s.

00:52:11.640 In their 80s.

00:52:12.640 Any sort of biological gifts or genetic gifts that those men had and or fact that they started

00:52:19.220 to train, you know, probably be very physically active as youngsters and were maximally physically

00:52:24.300 active from age, you know, 13, 14 to probably 30 would account for that.

00:52:27.920 And I think 30 would be a terrific goal. But I think the other thing too is how many push-ups

00:52:33.900 do you want to be able to do and how many sorts of body weight type of things do you want to be

00:52:37.540 able to do? What sort of agility maneuvers do you want to be able to do? And I think, you know,

00:52:41.840 you have to factor in orthopedic problems and that sort of thing. But again, we have good treatment

00:52:46.160 for those now. And our orthopedic surgeons can fix a lot of things that otherwise would have made

00:52:51.080 people difficult for them to walk and move around.

00:52:53.100 Yeah, we think a lot about those things. And we think that strength and stability need to be

00:52:57.040 trained in parallel and as hard as we're training from a cardio standpoint. But I do think this idea

00:53:03.040 that if you're trying to reverse engineer ending your life with a VO2 max in the mid-20s to high-30s,

00:53:11.600 the good news is you are never going to not be able to do something that you want to do.

00:53:17.760 If you're in the airport and the escalator isn't working, you don't care.

00:53:23.260 Yeah, right. And I think the thing you have to ask people, and this really resonates, is do you want

00:53:28.880 to be able to play with your grandchildren? That's one question for people. The escalator question,

00:53:33.280 that's a terrific question.

00:53:34.840 I was just in the airport last week, escalator down, and it's a long one. It was one of those

00:53:38.220 really long ones. You got your carry-on bag plus your backpack and you got to get up the escalator.

00:53:42.500 Now, I'm sure somewhere out there there was an elevator, but the point is, do you want to be

00:53:46.940 able to do this stuff? And if you do, then you have to do the math.

00:53:50.760 You have to work that. Agreed. And what's interesting, you see a few people around here

00:53:56.120 in rural Minnesota who grew up on less than fully mechanized farms and remained active milking cows

00:54:04.360 and doing these sorts of things, doing a whole lot of chores. It's remarkable the muscle mass that

00:54:09.720 some of these men and women have. Well, and if you look at in Japan, for example, and

00:54:14.160 the hilliest parts of Japan and some of the hilliest parts of Italy and Greece are where

00:54:18.540 the longevity is the highest. And people have argued it's because people have to walk up and

00:54:22.420 down the hills. And also, they keep their balance. They keep their glute strength. They don't fall.

00:54:26.620 That sort of thing, Peter. And also, that they're living a more rustic lifestyle is probably getting

00:54:31.340 them some de facto strength training on a daily basis.

00:54:35.000 Let's talk a little bit about VO2 max again in terms of what is actually driving it. So let's

00:54:41.260 go through all the variables. You've got gas exchange in the lungs.

00:54:45.280 In the lung, correct.

00:54:46.500 Then you have pump efficiency.

00:54:47.940 Correct.

00:54:48.400 We went through the mechanics of that again, but just so people understand what we talk about.

00:54:51.720 You've got stroke volume, contractility, of course, afterload and preload and all these things

00:54:57.580 that determine basically the efficacy of the pump to move the medium to the capillary bed. And then you

00:55:03.360 have capillary exchange in the muscle bed. So broadly speaking, let's just say those are three

00:55:08.140 variables, right? You've got the gas exchange at the source, you've got the pump, and then you've

00:55:12.800 got the gas exchange at the destination. I know that's overly simplistic.

00:55:16.360 So let's just think you got air to lung, lung to blood, blood from the heart to the tissues,

00:55:23.840 and oxygen from the blood to the tissues. There's four or five steps like that,

00:55:27.960 and you enumerated the three big ones. And so in general, oxygen uptake is cardiac output,

00:55:35.240 how much blood you're pumping per minute times arteriovenous oxygen difference, how much blood

00:55:39.540 you're extracting or oxygen you're extracting out of the blood. And it turns out that if you look at

00:55:45.540 all the studies and all the people fit, unfit, trained, untrained, in general, the biggest issue is

00:55:51.760 how much blood can you pump? So what is that heart rate times stroke volume equation? Where does that

00:55:57.680 leave us? Now, when you train, you get so you can extract more. And if you're at high altitude or if

00:56:03.220 you've got problems in your lungs, maybe the lungs don't work as well. But in general, I like to tell

00:56:07.860 people you cannot extract what has not been delivered. So the key is delivery, and that's

00:56:13.140 heart rate times stroke volume. And interestingly, Peter, as you, I'm sure you've seen, is some of your

00:56:17.960 fittest people actually have slightly lower peak heart rates. And one of the reasons is, is because

00:56:22.820 their stroke volume is so high. One of the really interesting, again, experiment of nature patients

00:56:27.160 or subjects is a man called Eskild Eberson, who won gold medals in five Olympics and rowing for

00:56:34.220 Denmark. They have serial VO2 max date on him from the time he was 18 or 19 until his early 40s.

00:56:40.860 And his VO2 max date around, you know, 5.6 liters per minute, which is quite high. And he weighed about

00:56:46.540 70 kilos. I believe he's a lightweight rower. But his peak heart rate dropped from about 190 to 150

00:56:52.160 over that period of time, which all that means is that he was able to pump the same amount of blood,

00:56:57.720 but he had to do more with each beat. That's an insane example, actually. So in other words,

00:57:02.640 in the individual, as they age, we think that the majority of the reduction in VO2 max is coming from

00:57:08.860 cardiac output reduction. Right. And the majority is probably coming from a reduction in peak heart rate,

00:57:14.180 which can be buffered to some extent if you have a nice compliant ventricle, like we talked about.

00:57:19.900 I'll tell you, I'm not quite yet 50. And I am just saddened by the reduction in my peak heart rate.

00:57:26.600 It is really breaking my heart. I mean, I...

00:57:29.380 Mine was never very high anyway, and I don't worry about it, you know, but I'm 63. So I stopped

00:57:33.660 worrying about it. I just, I worry about where my workload is.

00:57:36.460 I remember thinking like, there will never be a day when I can't get my heart rate above X.

00:57:42.240 But actually, I'll tell you, for me, it fell quite precipitously in my 20s. So as a teenager,

00:57:48.620 when I was training obscenely hard, inappropriately hard, a heart rate of 200 was an everyday

00:57:54.520 occurrence. There was never a day in high school that my heart rate didn't hit 200 to 205 beats per

00:58:00.420 minute. By the time I was in medical school, so 24, 25 years old, all of a sudden it dropped

00:58:08.040 immediately to about 180. It became very difficult to get over 180, which by the way,

00:58:13.140 was far lower than the 220 minus your age prediction.

00:58:17.640 I was in two famous studies as a subject. One is this lactate threshold study when I was 19.

00:58:22.400 And then a few years later, I went and worked one summer at Washington University in St.

00:58:26.260 Louis, and I stopped training. I had just finished my last year of track and field at the University

00:58:30.660 of Arizona. I'd run 10,000 meters in 30, 48 and didn't done well on the Pac-10s, which was a fast

00:58:36.880 time. Well, I was good enough to get lapped by the world record holders, is what I like to tell people.

00:58:40.960 But anyways, what happened is my peak heart rate was like 185 or 188. I can't remember. And over the

00:58:46.900 period of 12 weeks of detraining, it went up to about 10 beats a minute, which would have been,

00:58:51.520 you know, in the high 190s, which would have been, quote, 220 minus my age at the time.

00:58:56.360 There are all sorts of examples. There's a bunch of data on elite athletes showing that

00:59:01.280 some of them have peak heart rates similar to 220 minus their age, but many are lower than that.

00:59:07.240 And they're like Eskild Eberson. There are some people that have been world record holders,

00:59:10.640 Olympic champions that had peak heart rates in the 150s.

00:59:13.680 If I hit 170 today, that's a good day, which is about 220 minus my age.

00:59:17.780 That doesn't surprise me. My guess is I'd be hard pressed to get to 140.

00:59:21.960 I was talking with Lance Armstrong on a, had him on the podcast, maybe about a,

00:59:25.380 less than a year ago actually. And we were talking about back in the heyday of his tours,

00:59:29.700 they weren't really looking at their power meters when they were competing. So they trained with a

00:59:34.300 power meter when it was race day for the time trial, you just went off heart rate. And I was

00:59:40.460 just blown away. I mean, you got to think Lance was winning the tours between 28 and 35. He was still

00:59:47.360 holding 200 beats per minute for the entire time trial. So imagine 45 minutes at 200 beats per

00:59:55.360 minute when you're 30 plus years old is kind of insane.

00:59:58.820 The other example, there'll be a man named Bob Shule, who is an American who won the 5,000 in

01:00:03.280 1964, who did interval training all day and all night. It was incredible how he trained. And

01:00:09.240 I have the data someplace was like 154, 156. Jim Ryan's, the great miler was not particularly high

01:00:16.300 in his twenties.

01:00:17.480 Yeah. So just incredible stroke volume.

01:00:19.540 Correct. Correct. Correct. Big heart, big pumps.

01:00:21.980 All right. So let's talk a little bit about the training. Let's start with something that we

01:00:26.740 haven't talked about, which, you know, when you look at the best high output endurance athletes

01:00:32.200 today, it's one thing to talk about their peak engine performance, but it's easy to overlook what

01:00:37.520 they're doing at the low end. You know, I've had Inigo San Milan on the podcast twice, and we've

01:00:41.700 talked at length about Tadi Pogacar. And it's amazing to talk about how high his FTP is, his functional

01:00:48.520 threshold power. We could talk about his VO2 max, but equally amazing to that is how much

01:00:55.020 power he can put out while keeping lactate below two millimole. He's over four Watts per

01:00:59.860 kilo while keeping lactate below two millimole. Why that's amazing for someone who doesn't

01:01:05.160 ride a bike is if you took an average fit person off the street and said, hold four Watts

01:01:10.100 per kilo, they could maybe do it for a minute. Most people couldn't do it for a minute. And this

01:01:14.940 guy can do it for four hours. That low end aerobic efficiency, I always try to explain to my patients,

01:01:23.020 if your VO2 max represents the height or peak of your pyramid, the wider your base, the higher

01:01:28.400 your peak. Do you agree with that sentiment? What I would simply say is we think about

01:01:33.160 performance and you think about these elites, we think obviously about their VO2 max. Then you start

01:01:37.120 thinking about, you know, well, their lactate threshold, which would be sort of the FTP and

01:01:41.460 they're all sort of related anaerobic threshold. There's a lot of terminology here. You can get

01:01:45.900 in arguments with people about the details, but what fraction of your VO2 max can you perform at

01:01:51.840 for, you know, minutes to hours? And typically it's about 60% in untrained, young to middle-aged

01:01:59.080 people, lower in people that are really untrained, just sort of sedentary. People that are very fit,

01:02:04.400 it can be 75, 80, 85, even 90% of VO2 max. And in some older athletes, close to 100. So that's

01:02:12.220 exactly what you described. Somebody like that probably has a peak work rate that they could

01:02:17.100 sustain for 10 or 20 minutes of six, seven watts per kilo. So the fact that they can do four watts

01:02:22.620 per kilo forever shouldn't surprise anybody. You look at somebody like Mr. Kipchoge, you know,

01:02:27.460 who's running 440 miles at a pace that doesn't really probably cause much of an increase in his

01:02:32.600 blood lactic acid levels at all. Did they ever reveal any of those metrics when he...

01:02:38.420 That data has been published now. Tell me, what was his lactate level at the completion of the just

01:02:42.680 under two hour marathon? Remember at the end of the race, you wouldn't have a lot of carbohydrate on

01:02:47.140 board, but I would just simply say he can run 440 miles or over 12 miles an hour at levels that

01:02:53.000 barely nudges lactic acid levels. When I first started thinking about this and making models of

01:02:58.440 performance, I thought that the highest number was 85% of max. And it's probably closer to 90 for

01:03:03.760 somebody like him. And when you were talking about FTP for one minute, the other interesting

01:03:08.520 thing about that, Peter, is, you know, the Kipchoge challenge. People have put treadmills at 12 and a

01:03:13.440 half miles an hour. Yep. I've seen it done. Yeah. And see how long somebody can last on the treadmill,

01:03:18.180 you know, and it's like... Yeah, they're getting spit off in 30 seconds. Yeah, less than that.

01:03:21.920 It's insane. So same sort of thing. That sort of training, you know, for... And these people are

01:03:26.400 training two, three, four hours a day. If you look in terms of the runners, running is limited to some

01:03:33.020 extent because of... Yeah, the impact just becomes a problem. You know, orthopedic issues, the impact,

01:03:38.080 right. And so it's really difficult for people to run more than about 120 or 130 miles a week and

01:03:44.220 ever run too hard training for long periods of time. Now, there are a few people who can do it.

01:03:49.560 And if you look at what Kipchoge does, it's almost identical, even day for day, what Bill Rogers and

01:03:54.440 Frank Shorter did. Does it at altitude, but there's a lot of medium eight and 10 and 12 miles

01:04:00.500 of runs, a couple of hard interval sessions per week and, you know, long run. And that gets them

01:04:07.020 to 120 miles a week, you know, week in and week out. Now the cyclists can do more.

01:04:11.400 They don't have the impact.

01:04:12.340 Because you don't have that issue. But remember that with cycling, you know, you're going up and

01:04:17.460 you're going down and you have always a chance to take a break here and there. The swimmers do a ton

01:04:23.240 as well, you know, and again, because swimming is very forgiving in terms of not beating people

01:04:28.300 up, provided your shoulders, you know, don't get a bunch of tendonitis. But what's amazing is,

01:04:32.880 is that if you look at what the elite of the elite are doing, it does not really change that much for

01:04:37.760 50 or 60 years. You have better equipment, you have better races, you got better this, better that. 0.92

01:04:42.760 But in terms of, if you look at the data on the elite of the elite from the late 60s and early

01:04:48.400 70s, it's not like Kipchoge's VO2 max was 90. It was high 70s, just as what you would anticipate

01:04:54.900 and so forth. I think a lot of what's happened in terms of, at the very edge of things has been

01:05:00.960 better races. People that have longer careers, they don't stop when they're 25 or 26.

01:05:06.940 Sports medicine is better. So if they get injured, they can recover. We saw this last night with Clay

01:05:11.320 Thompson. He had two injuries that 30, 40 years ago would have been basically career ending.

01:05:17.120 And he's come back from a combination of an ACL issue and Achilles especially used to just

01:05:22.220 destroy people and he's playing very well. So I think those sorts of things, the races are much 1.00

01:05:26.900 better, you know, and they used to run the Boston Marathon at noon when every so often you'd get a,

01:05:31.820 you know, a really hot day. So most of the improved performance can be equipment, these sort of social

01:05:37.820 factors. Unfortunately, in the case of Mr. Armstrong, people, you know, bending the rules and so forth and

01:05:42.620 so on. So let's talk about kind of the intensity levels that one needs to be training at. I mean,

01:05:47.980 we could pick the most extreme example and talk about Kipchoge. How many hours per week is Kipchoge

01:05:53.760 running? Because I know he also does a ton of other strength training and bodyweight training.

01:05:57.900 My guess is that the total amount of time he's running is somewhere between 14 and 18 or 20 hours

01:06:04.280 a week. Yeah, he's covering a much greater ground, of course. You know, if you looked at it in terms of

01:06:09.160 the lactate threshold or the equivalent of critical power on the bike, probably 60, 70% of that is

01:06:15.780 fast, but not that fast. They typically start off their group run sort of jogging and then they pick

01:06:21.400 it up over time. Also remember that he's doing this at, you know, 7,000, 8,000 feet. And then my

01:06:27.420 understanding in reading his training program is a couple of days a week, he goes to a track and they

01:06:32.700 run multiple 400 meters, let's say 200 meter jog or multiple kilometers with a 200 or 400 meter jog,

01:06:40.360 like 10 times a kilometer, very fast. So the total amount of time he's running faster than Ray's pace

01:06:46.520 might just be 10 miles per week. So he's probably running about 60 or 70% of his stuff. Some of it

01:06:52.900 quite slow, but most of it, you know, medium fast, but certainly not where he's can't talk to you where

01:06:58.180 he's short of breath. Then he's probably spending about 20% of his time. He can still talk to you,

01:07:03.340 but he's pushing it a little bit and probably 10% of his time where he's pushing it a lot.

01:07:07.280 I mean, that's exactly my impression. And it's the same impression I have of elite cyclists and

01:07:11.760 elite swimmers. Those sorts of breakdowns, kind of the 60, 70, 20, 30, 10 are pretty typical. Now,

01:07:18.580 what's interesting is that's really emerged the last say 20 years. If you look at people who've

01:07:25.720 looked at the history of training and they have gotten training logs from people. And I told you,

01:07:31.100 we have lab data on people that's quite good starting in the 19, some even in the 1930s,

01:07:35.900 but certainly by the fifties and sixties, we've got plenty of good data. And if you look at what

01:07:40.980 these individuals who have tremendous treadmill values, tremendous VO2 max values, ran very fast

01:07:46.580 times on like dirt tracks and muddy conditions, that sort of thing. What we'd describe as a kind of a

01:07:51.420 kludgy bike now, certainly no aero bars. Look at the swimsuits people were racing. So if you look

01:07:55.980 at what those people were doing, they were doing all kinds of things. Runners in the sixties,

01:08:00.320 there were people again, like Bob Shule, a fascinating man who's still alive. His morning

01:08:05.300 workout would be 40 times a hundred meters with a short jog in between. And his afternoon workout

01:08:11.240 might be 20 times 400 meters. And he rarely ran continuously at all, except in races.

01:08:16.860 And it would be a fast interval slow. And there are other people who ran up to 200 miles a week

01:08:23.060 and hardly ever ran fast, again, except in races and some strides. There were already people doing

01:08:27.640 the sort of mixed training I described a minute ago. So what is interesting is the extent to which

01:08:32.700 things have sort of converged on this 60, 70, 20, 30, 10 sort of model. It makes sense if you've ever

01:08:40.020 done it yourself. And I can understand why there is a benefit to just the mitochondrial efficiency that

01:08:45.500 comes from the continuous effort that you'd miss out on if you were just doing the short bursts.

01:08:50.360 And similarly- Yeah, right. You'd make more money. Sure.

01:08:52.940 Yeah. Well, it depends what short is. I mean, again, if you're moving to 400s and to 800s-

01:08:57.200 Unless you do a whole lot of them. And the recovery is a jog because these guys aren't walking.

01:09:02.220 Do you think there is a training benefit? I know there's a health benefit, but a training benefit in

01:09:07.960 the lowest. So we kind of think about zone two as where Kipchoge is probably spending 60 to 70% of his

01:09:14.140 time. He can still talk. And then obviously he's in zone three, four kind of race pace. And then

01:09:19.860 he's like four, five, 10% of his mileage, which is really stretching himself. Now, is Kipchoge or

01:09:26.060 other athletes deliberately putting time into zone one, which is truly a recovery pace or-

01:09:32.000 Yeah. They do that when they're recovering between intervals. And you would be amazed at how,

01:09:38.540 because I did it many, many years ago. So the first mile or two can be very slow. It can be just

01:09:43.780 almost a walk, jog, and then they kind of drift into it. But thinking about the listeners who are

01:09:48.560 just trying to improve their health, that's where you come back to physical activity, you know,

01:09:51.800 versus intentional training. You start looking at the health benefits of just less than brisk

01:09:56.980 walking. You know, purposeful, but not really brisk walking. They're substantial. You know,

01:10:02.000 parking your car farther out in the parking lot and strolling in. I think, you know, walking the dog.

01:10:07.800 And that can mean all sorts of things, depending on what kind of dog you have and who's in the

01:10:12.360 neighborhood. The data on gardening. You could be out there hacking away weeds with a machete,

01:10:18.520 but most of us think about gardening as relatively light exercise. The health benefits of light

01:10:23.440 physical activity, light exercise are substantial. And remember, you're correct in the sense that,

01:10:29.500 at least from our perspective, there is no J-curve and things go up. But it's not completely linear.

01:10:35.960 The biggest benefit people get health-wise is the first 10 or 15 minutes a day.

01:10:40.580 And why do you think that is?

01:10:41.720 If you look at what 10 or 15 minutes does, I mean, I think it begins to do things in your

01:10:46.540 scalable muscle that improve your insulin sensitivity and help you fight against diabetes. I think just a

01:10:51.860 tiny bit of additional physical activity is at least some buffer against weight gain. I think that

01:10:57.560 there's some improvement in your aligning in your blood vessels and probably some improvement in

01:11:03.120 your autonomic function. Is your heart going to get bigger? Are you going to get a more efficient

01:11:06.880 cardiac pump? Probably not. But are you going to begin to do some of the things? And the answer is yes.

01:11:14.260 So, Mike, should those of us who really kind of care about this and care about using as many

01:11:18.640 metrics as we can to understand this? Should we be looking at heart rate recovery and adding that

01:11:23.040 to our kind of repertoire of something we track in ourselves as we train?

01:11:27.300 I think that there are people that are really into tech and monitoring, and then there's sort of

01:11:31.460 tech nudies. I'm a tech nudie. And part of the reason is there wasn't as much around when I started.

01:11:37.700 I mean, we just were getting digital watches and they weren't even stopwatches. And the other reason

01:11:42.100 is at the time, one of the big innovations was rating of perceived exertion. You know,

01:11:46.720 the 6 to 20 scale or some people use a 1 to 10 scale about how hard you're working. And I think

01:11:51.780 that what's been shown is because, you know, you can have a good day and a bad day in terms of the

01:11:55.460 metrics, that they're all sort of parallel. And if you learn to read your own body via, you know,

01:12:01.660 the rating of perceived exertion and or metrics, you know, find one you like and then just focus on

01:12:07.060 sort of big picture things. So, I would not get too hung up on heart rate recovery and too hung up on

01:12:13.060 heart rate variability. I would just more say, how much are you doing? 30, 40, 60, 180 minutes a week.

01:12:19.180 Are you also doing other forms of, not a week, a day? Are you also doing other forms of activity,

01:12:25.860 you know, like taking the stairs, as you mentioned? And what sort of combination are you doing? How much

01:12:31.600 time are you spending where you're really short of breath? How much time are you spending where

01:12:35.520 you're a little bit short of breath? And how much time is it kind of a pleasant sort of pace?

01:12:41.040 I think that that sort of information can get you as much as you need. And I think the main thing

01:12:46.640 then, Peter, is to make sure that you have some accountability, whether it's a training partner,

01:12:52.680 maybe with a device or a diary, maybe, you know, with just how far did I run today?

01:12:59.040 That sort of thing. So, what is your current exercise regimen? I mean, you sort of downplayed

01:13:03.620 it a minute, but 30 minutes and 40 seconds for a 10K, I don't think people understand how fast that is.

01:13:08.500 I once ran a 225 marathon, but, you know, the older I get, the better I was, right?

01:13:12.860 I'm a big believer in what's called hard easy. Hard day, easy day. What I'll do, like tomorrow,

01:13:19.020 will be a hard day. So, I'll get on, you know, a stationary bike in my workout room,

01:13:24.060 on the bike and the rowing machine, do some sort of warm-up for 10 to 15 minutes.

01:13:28.240 Then I will do a circuit that starts with 25 squat thrusts, a minute of jumping rope,

01:13:34.960 static wall sit to failure, and then some drop sets where you go down the weight stack.

01:13:40.480 Then drop sets with incline flies, then drop sets with leg extensions, and drop sets with a

01:13:47.040 combination of pull-ups and lat pull-downs and military press. Then some additional stuff for my

01:13:53.920 legs, push-ups, bar dips in, upright rows, followed by something else for my legs. So,

01:13:59.920 I alternate arms and legs, and I work my way through this with no rest. Drop sets on each

01:14:04.120 thing for all large major muscle masses, and that takes about 22 minutes.

01:14:08.180 22 minutes for one circuit.

01:14:09.860 One circuit. Then I get on the bike, and I'll do like eight times three minutes of a ladder where

01:14:16.380 you start unloaded, go up a notch, go up a notch, go up a notch, and I get to maybe about 350 watts

01:14:22.160 for the last 30 seconds, come back down to about 100 watts, 350 watts, do that times eight.

01:14:27.660 And sorry, how long do you take the ladder? Three minutes?

01:14:30.080 Three minutes. Something like 100 watts for 30 seconds, 150 for 30, 200 for 30, 250 for 30,

01:14:37.320 300 for 30, 350 for 30, come back down times eight. And that takes about an hour.

01:14:42.760 And how long in between your three-minute sets?

01:14:45.480 No, you just go up and come right back down.

01:14:47.140 Your rest from the...

01:14:48.040 So, the recovery is... Exactly. That takes about an hour, and that'll fix your wagon for a while.

01:14:53.140 That'll be your hard day tomorrow, and then what...

01:14:55.200 That'll be my hard day, and I'll do that basically every other day or every third day.

01:14:59.800 My easy days will be something like, this morning, I want to go do 20 more minutes,

01:15:03.920 not because I need to do 20 minutes, because I wanted to watch the first bit of Obi-Wan Kenobi.

01:15:08.720 So, all my easy days are built around what documentary or, you know, how many times can

01:15:16.140 you watch The Mandalorian? How many Clint Eastwood movies can you watch? And this started during

01:15:19.760 lockdown, right? So, my easy days are 30 to 40 minutes of light cycling, transitioning to rowing

01:15:26.320 back and forth of around 30 to 40 minutes. Sometimes I do one. Sometimes if I come home

01:15:31.340 from work, I do another one. But the goal there is an old concept called active rest.

01:15:37.020 So, I'm not trying to get a real training effect. I'm trying to loosen up from the day before

01:15:41.940 this workout, because I'm sore. You do what I described. You warm up for 10 or 15 minutes,

01:15:46.960 do 20 minutes of drop set, and that type of intervals at the end, you will be sore, right?

01:15:52.080 So, you have to recover the next day. Now, I'll do this for about six months,

01:15:55.520 and then probably when it starts getting dark again, I'll do what I did like last year,

01:16:00.100 where I start just doing kind of maintenance circuits in terms of the strength,

01:16:04.180 and maybe only twice a week. And I'll start doing longer rides. We have a Peloton.

01:16:09.060 I don't do any of the classes, but I started doing this hour of truth to see how many watts I could

01:16:14.040 average for an hour. Okay. What are you at?

01:16:16.680 I think my best during lockdown last year was 316, average 316 watts for an hour.

01:16:21.220 Wow. That's obscenely.

01:16:22.780 Yeah, that's pretty good for it. And the things are calibrated pretty well. I got a lot of equipment.

01:16:27.380 I got a watt bike, and I think they're pretty close. If you look online, they claim they're close,

01:16:31.140 right? It's consistent with what I think. I haven't measured my VO2 max in a while.

01:16:35.620 So, I want to see if I can get like 320 watts next year.

01:16:38.460 What do you think your VO2 max is right now?

01:16:40.440 Well, I'll tell you, back when I was quite young, it was 5.4 liters a minute.

01:16:44.000 At what weight?

01:16:44.880 My weight then was probably between 75, but close to 80 kilos. So, I was right at under 70.

01:16:50.640 I think my weight now is probably about 95 kilos because I've actually made an effort to gain some

01:16:55.200 weight. And I think my max is probably 4.5 liters a minute, would be my guess.

01:17:01.340 That's still an amazing wattage under any circumstance.

01:17:04.920 Assuming the machine is okay, but I think it is because remember when I'm doing those ladders

01:17:09.100 that I was telling you about or those pyramids, that's after I've done a heavy leg workout.

01:17:13.060 You know, so my legs are pretty fatigued when I've done that. But remember, I have some ability

01:17:17.480 too because...

01:17:18.580 Well, clearly given what you ran, yeah.

01:17:20.320 I didn't really start running until my senior year in high school, so I started late. And I'm 6'4",

01:17:24.860 and I like to tell people if I come back at the next life, I'll be a swimmer or a rower because I

01:17:28.860 used to show up with these tidy people. I'm the world's largest relatively good distance runner.

01:17:33.980 Formerly relatively good.

01:17:35.540 On your easy recovery day, Mike, are you just paying attention to RPE or are you looking at a

01:17:40.920 split time on the rowing machine or as a low wattage bar on the bike?

01:17:44.900 No, no. It's just all RPE. It's really just active rest, which is a lost

01:17:49.920 concept.

01:17:51.080 Do you have a sense of what your heart rate is as a percentage of your max heart rate?

01:17:55.280 No, I don't even measure it. It's probably about 140 is my peak heart rate. That would be my guess.

01:18:01.060 Again, I go with RPE. I go till I suffer. It's unusual to be able to do intervals on your own

01:18:06.260 and really push it. Not everybody can do it. And that's why you need a class or you need a coach or

01:18:10.780 you need a group and so forth. But I'm lucky enough to be able to do it. So my training is really

01:18:16.280 polarized. I mean, like really polarized.

01:18:18.140 So let's talk about folks who are listening to this who want to boost their VO2 max. Let's talk

01:18:24.840 about the different protocols that exist. I'll tell you what we typically tell patients to do,

01:18:30.060 which is in my experience, one of the most efficient ways that you can do it. But I'm

01:18:34.500 curious as to what other ways. So we typically talk about a four by four, four on four off protocol.

01:18:39.140 So we'll tell people. And again, the easiest way that I personally can do this is on a bike

01:18:44.960 on an incline. And it can't be a very steep incline. It's got to be like 6% grade. I want to stay in the

01:18:49.780 saddle, but I never want the resistance to go away. And I basically want to be in the saddle climbing

01:18:56.460 against resistance for four minutes. And I use a power meter and a heart rate. So I just want to keep

01:19:02.180 the power as steady as I can. Invariably, it dips in about the third minute, and then I can recover

01:19:08.180 it in the fourth minute psychologically. And then the recovery is four minutes of literally doing

01:19:13.660 nothing but rolling back to the starting line. And then it's basically just repeat that.

01:19:18.260 No, no, I'm with you. What I tell people, for example, that have come and say, I want to run a

01:19:21.780 faster marathon. I want to do this. I want to do that. And they're running a lot of miles.

01:19:25.120 They need to get their VO2 max up. And I tell them exactly what you've described.

01:19:28.700 Sometimes I tell them five minutes and three minutes rest, sometimes whatever.

01:19:32.660 And people that are fitter, sometimes only take, like I would only take two minutes of rest.

01:19:36.820 But four times four is terrific. So you would do something, if you were thinking about running,

01:19:42.960 I would tell people to do something that would be right at their sort of 5k race pace,

01:19:47.820 maybe a little faster, or you would do the first one a little slower than your 5k race pace.

01:19:53.160 The next one, you know, a little faster than that. The next one a little faster. The next one

01:19:56.980 faster than your 5k race pace. And depending on how fast you're running, if you're going pretty

01:20:02.220 fast, then you would just jog in between. And if you were not going so fast, you'd walk in between.

01:20:07.320 So that would be the sort of thing that I would describe to people. The classic training,

01:20:11.940 you know, among elite runners is mile repeats, you know, four or five times one mile. And then they

01:20:19.380 jog a quarter mile or half mile in between. And I personally have seen really good runners

01:20:24.360 do, you know, 430, 425, 420, 415, 410, 405. But I mean, these were people getting ready for the

01:20:33.000 Olympics. But sort of for the average person, the hard part that I think requires a little bit of

01:20:38.220 coaching up front is, you know, you and I have done this our whole lives. So we sort of know what

01:20:43.220 four minutes all out feels like. At 30 seconds in, you shouldn't be hurting too much. If you are,

01:20:49.360 you've gone out too hard. It takes a little bit of work to coach somebody to understand

01:20:54.100 what you're going for is a constant four minutes. But the suffering is disproportionately in the last

01:20:59.760 90 seconds. When you get done with the last one, the fourth one, you do not want to be bending over.

01:21:05.060 If you'd have gone a little bit of faster, you'd want to be bending over. So I call it the no bend

01:21:09.020 over rule. And then what people have to recognize, both for the four times four minutes and within the

01:21:15.420 four minutes is a good interval workout. And this sounds completely masochistic is like putting

01:21:21.580 your hand in warm water and then slowly increasing the temperature in the water to where you can

01:21:27.940 barely stand it anymore and then leave it in for a while. And then you turn it down, let your hand

01:21:33.480 cool off and do it again. One of the things I think we've learned from the cyclist is a terrific

01:21:38.260 phrase called manage your suffering. You know, you need to learn to manage your suffering.

01:21:42.840 And I think that's the other interesting thing about this type of training is to the extent,

01:21:48.300 you know, people can have these sort of religious experiences exercising.

01:21:52.120 This sort of interval training is one way to get them.

01:21:55.180 No, I completely agree. I mean, obviously, we're cut from the same cloth in this way. But I think

01:21:58.880 that there really is something wonderful about experiencing your limits and understanding that

01:22:04.880 level of discomfort.

01:22:06.580 And if you're able to maintain your rhythm and tempo, Peter, while you do it, that's when you can

01:22:11.620 have these sorts of experiences. I mean, one of the most beautiful things ever, and it wasn't a

01:22:16.000 total endurance, you know, even it was a little bit short, a couple of minutes. But to watch Michael

01:22:20.420 Phelps swim the butterfly and watch his stroke, he was good at everything, but he was especially good

01:22:25.720 at the butterfly. Most people's stroke has fallen apart and they end up taking more strokes the last

01:22:30.800 50 of a 200 meter butterfly. You know, his stroke count, the second, third and fourth lap didn't change

01:22:36.900 because he had that rhythm, that tempo. And if you listen to the old school coaches

01:22:41.080 talk about interval training, they're constantly talking about tempo. What is your rhythm? What is

01:22:46.760 your tempo? And why you're doing it, why you're suffering, Peter, why you're pushing it while it's

01:22:51.860 hurting, while it's burning. The goal was to not lose your form and not lose your tempo.

01:22:56.620 I used to watch Michael Phelps train before he kind of broke out in the early 2000s. I lived in

01:23:02.680 Baltimore because I did my residency at Hopkins and he used to train at a place called North Baltimore

01:23:06.760 Aquatic. Now, Michael, of course, within the swimming world was already an unbelievable prodigy

01:23:11.500 because he had gone to the Olympics in Sydney, placed fifth. At age like 15 or something, which

01:23:16.860 is quite young for a man. That's right. He became the youngest male to ever set a world record in a

01:23:22.240 time sport in early 01. He was still 15. When he, yeah, set the record for the 200 fly. So watching this

01:23:29.660 16 year old swimming at North Baltimore Aquatic and BAC, which his signature event of course was

01:23:35.740 the 200 fly. Now it's 200 long course butterfly. I would put that up there with the 200 breast and

01:23:42.180 the 400 IM as the three worst races in all of swimming. To me, it's like doing an 800 meter

01:23:47.900 intermediate hurdles on the track that event doesn't exist. It's insane suffer. But here's the

01:23:53.920 thing, Mike, his training, you never once saw him do a 200 fly. It was lots of 75s, lots of 75s. And

01:24:03.920 his coach, Bob Bowman was really adamant about perfect form. Because if I recall, Michael had an

01:24:10.040 unusual rhythm, which is that he breathed on every stroke. And when most people swam butterfly,

01:24:14.920 it was every other, you were head underwater for one stroke, head up for one down for one. Michael,

01:24:20.220 I'm pretty sure he would breathe every stroke. But as you pointed out, no one's form could rival his.

01:24:26.620 And that's why he was usually the last guy to hit the wall at the 50, yet would come back and just

01:24:31.680 devour everybody. And you see that with Edwin Moses, 13 steps between hurdles in the 400 hurdles in the

01:24:37.700 late seventies with that innovation. You see these people, you start with Kipchoge doing it for two

01:24:43.040 hours, their ability to maintain this form and tempo. And as you watch it, as you watch it, Peter,

01:24:48.880 you are awed by this sense of great effort and simultaneous relaxation. It's a real paradox.

01:24:55.720 You see that in other sports too. You see it when golfers get hot, how far they hit the ball,

01:25:00.480 both violent and relaxed at the same time. You sit there and watch Steph Curry or Clay Thompson

01:25:05.440 start launching balls. And it's just incredible, the tempo, the rhythm, the form, and the effort. But

01:25:11.340 again, just how relaxed they are. It's just wild to think about even.

01:25:15.540 Now going back to our very, very recreational person who's never trained in their life,

01:25:21.160 we don't use lactate testing on people at that level. We basically do the whole thing off RPE

01:25:25.860 and we try to get 80% of their time, which might start out at two to three hours per week as we

01:25:32.780 want you to be able to talk, but not enjoy it. I don't want you to be any higher than that.

01:25:37.580 And then once we build up a bit of a reserve in that, after maybe six months of that kind of

01:25:42.180 training, we're sort of ready to move them to that next phase of, Hey, once a week, I want you

01:25:47.780 to do kind of four on four off for four rounds. Do you think that once a week doing four hard

01:25:55.100 intervals is sufficient to boost VO2 max? It will increase it for sure. In that vast majority of

01:26:01.380 people, especially if they're doing the other stuff you're talking about, what I really liked about what

01:26:05.380 you describe and what people don't realize, especially when you're going to advocate relatively hard

01:26:09.880 training for citizens, is that sometimes you have to train before you can really train.

01:26:14.420 That's right. You got to train to train.

01:26:15.740 You've certainly seen that in some studies with people that are really 60, 70 years old,

01:26:19.960 is that they almost have to do three or four or six months of sort of pre-training before they

01:26:24.340 are fit enough to train hard. So I think you're spot on there. My guess is after they've been able

01:26:29.380 to do it for once a week for a while, you build them up to two times per week. I think the one thing

01:26:34.700 that people need to recognize, and this comes from a man named Stan James, who I think is still

01:26:39.620 practicing medicine. He's in his 90s. One of the pioneers of sports medicine, orthopedic surgery.

01:26:44.680 He's not operating anymore. The last I checked, he was alive and well out in Eugene, Oregon.

01:26:49.220 He worked with coach Bill Bowerman, you know, the great Oregon coach, one of the founders at Nike,

01:26:53.600 the waffle shoe guy. You know, and they got into this hard, easy thing, which is sort of what I do.

01:26:58.380 And I, you know, Dr. James would tell you that once people start doing more than about five or six

01:27:03.080 hard sessions every two weeks, you're beginning to ask for some sort of load management issue,

01:27:08.780 whether it's orthopedics, whether it's just you're fatigued, whether it's this, whether it's that.

01:27:13.240 So I do think, I can't remember the last day I didn't do anything. You know, it's probably been

01:27:18.440 years, but my guess is the number of times I do something hard is, you know, 120, 130 times per year.

01:27:26.000 And my guess is I'd never go more than a week without doing something relatively intense.

01:27:30.700 When you think about these sort of exceptional elite athletes, the Kipchoge's of the world, 1.00

01:27:35.860 do you believe they have a finite number of exceptional performances in them?

01:27:40.620 You know, people used to drift into the world rankings and they'd last, you know, maybe two

01:27:44.460 Olympics, six, seven years. So they'd come in, kind of emerge right before one Olympiad,

01:27:49.780 do well, do well in the next one and kind of fade. But I think there's two things that have really

01:27:54.740 changed. The first is that again, sports medicine is better. So if people do get injured,

01:27:59.180 they can do things about it. And I think the second thing is just become so professionalized.

01:28:03.440 People can, that are really, really good can now make enough money to make it worth their while

01:28:08.580 to continue. You know, you see this in terms of the age of Olympians, you know, it used to be very

01:28:14.860 unusual to have women over age 20 and swimming. There was no college swimming. There was none of this. 0.98

01:28:19.740 There was none of that. So it was a lot of teenagers. Now you see that drifting up and you see

01:28:23.840 people like Katie Lodecky having extended careers. Phelps going 2000, 2004, 8, 12, and 16 going to

01:28:32.180 five Olympics. Yeah. That would have been inconceivable previously for swimmers. You know,

01:28:37.140 people hung around and maybe stayed for one additional Olympics when they got done after

01:28:40.940 college, sometimes two, but eventually they had to go get a job. But again, among the most elite who

01:28:46.960 can now monetize this, people can last longer. And you see it also in quote, the major unquote,

01:28:52.320 professional sports, you know, before orthopedic surgery was good and every knee surgery was an

01:28:57.440 adventure, you know, somebody like Tom Brady. Yeah. His career would have been over in 2009.

01:29:02.540 And the other thing, Peter, is if you're making a hundred thousand dollars a year, why keep playing?

01:29:06.540 If you're making, you know, 23 million or however, whatever the number is, you know, why not keep

01:29:11.980 playing? And you look at in sports like running, swimming, cycling, you know, that's less of a kind of a

01:29:16.480 journeyman group. But if you look at the NBA, the NFL, major league baseball, the salary scales are

01:29:22.000 pretty good. And if people can play another couple of years, you know, this can be millions of dollars,

01:29:26.160 millions of dollars for them. So they're very motivated to do this. If you can be the eighth

01:29:31.660 man on the NBA team and give people 15, 20 quality minutes of a game, you know, you're going to have

01:29:36.660 a job for a long time. And again, if you're LeBron, you know, who apparently spent some huge amount

01:29:41.300 of money on training and cook and all that other stuff. If you start thinking about spending X per

01:29:46.520 year for a 40 X paycheck, why not? Why stop?

01:29:51.500 So where do you think we are today, Mike, in performance enhancing drugs in sports? So cycling

01:29:58.540 is probably the sport I would follow the closest of the major endurance sports. I guess I follow

01:30:03.460 swimming as well, though not nearly as much as I did for 15 years prior. You know, I think when you

01:30:09.080 go back and look at the cycling data, I love the way Lance talks about this, right? You know,

01:30:13.980 I think he's very open, right? To say, look, as long as there has been a tour de France,

01:30:17.820 there has been a graying of the line, but there is a difference between the kind of high octane

01:30:22.900 cheating that was done in Lance's era and sort of the low octane cheating that was done in Eddie

01:30:28.260 Merckx's era when they were using a little bit of MFET. Here's what I would say about where we are

01:30:33.100 with doping. So the testing has gotten better, both in terms of the frequency of testing and-

01:30:39.780 The ability to detect, yeah.

01:30:40.920 You know, the actual chemistry of the testing of the machines, the analytics.

01:30:45.000 If you look at the way what's called an abnormal test is called, it's not like what we call

01:30:50.660 an abnormal test or an out-of-range test in clinical medicine. There are typically many

01:30:56.560 standard deviations above average for these things, and they're typically designed so there's

01:31:01.480 not a lot of false positives. They don't want to have any false positives. So that gives people a

01:31:05.960 room, some room to micro-dose. And that's why you have relatively few positive tests.

01:31:12.600 But occasionally there'll be people, you know, caught through investigations, judicial mechanisms,

01:31:17.640 the police. And historically, many of the biggest busts have been the police. What I would simply say

01:31:23.880 is that the era of industrial strength doping is over. You know, people doing like the East Germans did 1.00

01:31:29.660 and androgenizing females to the extent that they really look like men. So I think that that is done. 0.87

01:31:35.960 You say that even in light of what the Russians did as recently as less than a decade ago?

01:31:40.380 I think what the Russians did was, again, relatively low dose by comparison. So I think 0.94

01:31:45.180 there's plenty of room for micro-dosing, plenty of room for the kinds of manipulation, systemic

01:31:49.700 manipulation, if there's a motivated government to do it. And there's plenty of room, you know,

01:31:54.700 for other forms of corruption. But I do think that industrial strength doping has largely been

01:31:59.300 quote, stop, prevented. I think there are probably a bunch of novel compounds that are out there,

01:32:05.600 you know, small peptides that cause this to be released or that to be released, which would be

01:32:09.880 very, very difficult to detect. They'd have vanishingly short half-lives and so forth. And

01:32:15.560 they would just boost your endogenous production of hormone X, Y, or Z, you know, something like a

01:32:21.040 growth hormone releasing factor, you know, something that caused testosterone levels to

01:32:25.040 go up or so forth. It's a cat and mouse game. I think for the kind of the big three amphetamines,

01:32:30.700 EPO slash blood doping and anabolic steroids slash growth hormone, I think that testing has gotten

01:32:37.040 better and industrial strength doping is over. We don't know what we don't know about these novel

01:32:43.140 compounds. And I think what we learned from the Ballco situation is that there are all sorts of,

01:32:48.820 you know, clever bathtub chemists who can make all sorts of things at home in the garage,

01:32:54.460 wherever it is in a very unregulated environment. And the barrier to entry for that kind of a do-it-yourself

01:33:00.980 sort of stuff is quite low. You can buy, you know, all sorts of laboratory equipment and reagents

01:33:06.060 and all sorts of things. So, you don't have to be, you know, a big pharma house to make

01:33:09.720 interesting things. That's where I'd say we are with doping.

01:33:13.000 How familiar are you with Ballco and the agents that we're...

01:33:15.480 Ballco and Patrick Arnold.

01:33:17.000 You know Patrick?

01:33:17.600 I don't know Patrick, but I know who he is. The tragedy of Patrick Arnold, this tremendous

01:33:22.360 guy with a master's degree, I believe, in organic chemistry, that he wasn't working for

01:33:26.320 one of the big pharma companies making anti-aging, anti-sarcopenia compound.

01:33:32.280 I've met Patrick a number of times. I've spent a lot of time speaking with him in a very unemotional

01:33:36.860 way and just a very frank way. He can explain in great detail exactly how he modified these androgens.

01:33:43.100 The guy has encyclopedic knowledge, apparently, of everything that's ever been synthesized in the

01:33:48.200 androgen field and what it does in terms of half-life and that metabolism and that sort of

01:33:53.060 thing. If you think about Victor Conte Jr., you know, a refugee from the Tower of Power, 1.00

01:33:58.540 junior college-educated rock-slash-jazz musician who's one of the great autodidects ever out there.

01:34:04.760 So I think with both of these individuals, step back from the legal ethical ramifications and say,

01:34:11.580 what do they know? And try to be a little bit objective about that. With doping, you get into

01:34:16.660 all sorts of other sort of areas. In the cultures those people were operating in, what was considered

01:34:23.080 the cultural norm? Lance was not the only person doing industrial strength doping. Was he doing it

01:34:29.400 better than other people? If there were six ways to dope and person X was doing two and you were doing

01:34:34.220 three, was Lance doing all six? That sort of thing. The other thing people have to recognize about

01:34:40.200 doping in these incredibly competitive situations with these incredibly competitive people,

01:34:46.900 competitive organizations or people that have, you know, foreign policy, our country is better than

01:34:51.880 yours because we won more medals, is that there's always going to be some sort of arms race mentality.

01:34:57.540 And you see it with training. You know, if you're in there lifting an hour a day, I'm going to go

01:35:00.440 lift an hour and 10 minutes a day. And so where does it stop?

01:35:03.180 Do you still think that growth hormone, human growth hormone, which is of course not something

01:35:08.280 that can readily be tested for, is still one of the more utilized agents probably even today

01:35:13.520 for performance enhancement? There's probably some of it going on. My guess is people are

01:35:19.160 probably have drifted back to more short-acting androgens, low-dose short-acting androgens,

01:35:24.320 and hope for the best. That would be my guess. The same would be true with low-dose EPO

01:35:29.400 and or sort of related compounds or other factors. When you learn about growth hormone is typically

01:35:36.280 because person X says that they're sending FedEx packages to athlete Y, you know, that kind of

01:35:43.120 thing. So much of this has a judicial slash, you know, investigatory element to it when you get to

01:35:49.660 the big scandals. Why do you think some sports seem more affected than others? So for example,

01:35:54.000 swimming as a general rule seems less impacted than say cycling or even running, even though the

01:36:01.400 demands are still pretty high. Hard to know. And how cultures head one way or the next,

01:36:08.040 tribalistic behaviors, what's normal, what's not normal, and so forth. I think that that's 0.97

01:36:12.820 key to understanding that sort of thing. We started this discussion, Mike, by talking about

01:36:17.860 the miracles of exercise, right? We went through all of these things that exercise is doing

01:36:23.000 physiologically and how the net impact of these things is so profound on the length of your life

01:36:30.940 and the quality of your life. There's no shortage of pharma companies out there that are trying to

01:36:36.940 understand how can those benefits be put into a pill. Exercise pills, sure. Exactly. What is your

01:36:43.980 level of optimism around the idea that some of the benefits of exercise could be basically captured

01:36:52.840 by a pharmaceutical strategy? The efforts for exercise memetics so far have been primarily things

01:37:00.180 that increase mitochondrial biosynthesis. And that appears like it at least works in animal models. And

01:37:06.660 then you always, how do you translate it from one to the next? But as I pointed out, exercise, sure,

01:37:11.280 it makes your mitochondria better or makes more of them. But making your mitochondria better isn't

01:37:16.640 going to make your autonomic nervous system better, isn't going to make your blood pressure better,

01:37:20.660 isn't going to necessarily make the lining of your blood vessels better, so on and so forth. So it's

01:37:25.060 not going to make your heart bigger, so on and so forth. So I think at least so far, at least so far,

01:37:30.720 these have been sort of one-trick ponies. And while you might be able to get some benefits for people

01:37:36.500 that are wheelchair bound or whatever, quadriplegic, let's put it that way, not even wheelchair

01:37:40.580 bound, can exercise for some other reasons, that may be helpful. I think the jury is really still

01:37:45.940 out. I'm not particularly enthusiastic about it. I don't think you're ever going to get one that does

01:37:51.680 any more than a little bit. I think more interestingly, I like to tell people, you know,

01:37:56.400 at some level, there's already an exercise memetic out there. It's called the poly pill.

01:38:00.080 But if you look at the data on people who get a combination, one pill a day of low-dose statins,

01:38:07.260 low-dose blood pressure meds, and maybe one or two other components, it causes pretty nice

01:38:13.180 reductions in risk factors in most people. Because doses are low, the side effects tend to be low,

01:38:19.500 and so forth. But again, none of this is patentable. But if people don't want to exercise,

01:38:24.920 can't exercise, you know, a better choice than trying to find some mythical exercise memetic is

01:38:30.960 to use a poly pill, which would do the same thing. She'd give them a statin, their cholesterol goes 0.98

01:38:35.640 down, and maybe their endothelial function gets better. You do a tiny bit of metformin,

01:38:40.140 maybe their glucose tolerance gets better. You do a bit of beta blockers, their heart rate is lower,

01:38:45.200 that sort of thing. And again, I'm not advocating this, but there's all sorts of data out there that

01:38:50.760 a poly pill, data and speculation and modeling suggesting a poly pill is a, quote, legitimate,

01:38:57.340 unquote, whatever that means, potential public health strategy for lifestyle diseases. I would

01:39:02.060 encourage people to exercise and do the sorts of things you're talking about, but I think poly 0.99

01:39:07.400 pills have been understudied. Mike, what is it you're most excited about right now? What is the

01:39:11.540 question you're most interested in trying to answer? I'm excited about a lot of things. We've got

01:39:16.600 some interesting data with Sarah Baker on sex differences in blood pressure regulation. I'm

01:39:21.320 quite interested in human performance. As you know, Peter, the first thing they teach in medical

01:39:26.180 school is that a right shift in the oxygen hemoglobin dissociation curve is good for you

01:39:30.200 at altitude. Well, all animals that are genetically adapted over centuries, millennia, to high altitude

01:39:36.720 llamas, the birds that fly over Mount Everest and so forth are left shifted. We've been doing some

01:39:41.220 really cool hypoxia studies in people with rare left shifted hemoglobins. I'm super interested in that.

01:39:46.820 Just as sort of a physiological question. Can you explain to folks what the right and left shift

01:39:51.300 looks like on the hemoglobin dissociation curve? Think of a curvilinear situation or an S-shaped

01:39:55.480 curve, an italicized curve. And so the idea is that if you shift it to the right, the red stuff,

01:40:02.000 the hemoglobin in your blood doesn't hold onto the oxygen. So it releases it and can give the oxygen

01:40:07.740 to the tissue. And that's great if it's hypoxic. Now, the problem with that is it's harder for that

01:40:13.300 kind of hemoglobin to get the oxygen out of the lung. And animals like llamas and like these incredible

01:40:20.140 athletes called the barheaded goose that fly over Mount Everest without acclimation. They're living in 0.58

01:40:26.480 the plains of Mongolia. One day they just fly over Mount Everest and go to India. They're left shifted 0.94

01:40:31.040 because they prefer to make sure that they can pick up the oxygen out of the air in their lungs

01:40:36.440 at very high altitude. So we have a family of people and some other subjects that we study that

01:40:42.500 are left shifted. Sorry, meaning there is a family of people who genetically shift left instead of

01:40:48.940 shift right under hypoxic conditions. And there's all sorts of rare hemoglobin variants. They're not

01:40:54.660 like sickle cell or anything like that. Very interesting, Peter, to be sitting in the lab having

01:40:59.160 somebody breathe in 10% oxygen talking to you. These left shifted people do that. It's crazy. It's just

01:41:04.200 wild. What is the FIO2 at the top of Everest, by the way, just for comparison? Barometric pressure

01:41:09.580 is about 250. So it'd be 21% of 250. So roughly about 50. So once you get in into your lung, I think

01:41:16.140 arterial is about in the 30s. Wow. Yeah. At 15%, which is 3,000 meters, these people exercise like,

01:41:23.300 you know, they do fine. So I'm very interested in that. And then as I mentioned, you know, before we

01:41:27.620 went on is through a weird collection of events, when the pandemic struck in March and early

01:41:34.160 April of 2020, I somehow became the principal investigator of the U.S. Convalescent Plasma

01:41:39.920 Program, a program that was initially designed to facilitate in 5,000 patients compassionate use

01:41:46.240 of convalescent plasma, antibody-rich plasma from recovered COVID patients that we would give to

01:41:51.600 people who had disease and hopefully the antibodies would help them. Through all sorts of twists and

01:41:56.180 turns, we ended up doing over 100,000 people. We found evidence if we gave people a whole lot of

01:42:01.180 antibody early in the course of disease, we made them better. We also found some evidence that it

01:42:06.340 was probably very helpful in people that were immune suppressed. And that has been the gift that

01:42:10.840 keeps giving. So at age 60, you know, 162, 63, I got kind of a new career in immunology and infectious

01:42:18.400 disease. And so we're pursuing that. And we're especially interested in that, Peter, because

01:42:23.580 whenever COVID sort of finally winds down, about 2% to 3% of the population is what we call B cell

01:42:31.560 deficient. So B cells are the cells in your body that make antibodies, help you respond to fight the

01:42:36.780 virus or respond to the vaccine. About 2% or 3% of the people don't have any or don't have very many.

01:42:42.080 And those people will continue to get COVID and other forms of infectious disease. And antibody

01:42:47.720 therapy is essential to help those folks. You know, I'm very happy that we've published papers in high

01:42:52.780 profile journals, but we just learned yesterday from People Magazine of all places that the actor

01:42:58.160 Jeff Bridges. The dude himself. The dude from The Big Lebowski. The dude himself had gotten lymphoma,

01:43:04.600 gotten drugs that depleted his B cells, which is typical for lymphoma patients. Got COVID, he could

01:43:10.760 not clear the COVID and responded to convalescent plasma. What's the total volume of plasma you need

01:43:15.400 to give a patient in that setting? If you get really high titer stuff, 2 to 400 mLs.

01:43:20.100 That's it. One-time treatment? Yeah, typically. Sometimes we give people more. And what's been

01:43:24.960 helpful, Peter, is that we now have people that have been both vaccinated and they've had a

01:43:30.500 breakthrough infection or they've had an infection and been vaccinated, right? So they have hybrid

01:43:34.100 immunity. And those people make, their plasma has a whole, whole lot of antibodies in them

01:43:39.200 and they're broad spectrum. So they cover all the variants and they almost anticipate future

01:43:45.360 variants because of the way the immune system works is a sort of a sloppy replicator. And so

01:43:51.360 they cover a lot of the variants. They cover potential future variants and as monoclonal

01:43:55.500 antibodies, which have been super helpful during the pandemic, as those get less effective due to

01:44:00.680 escape variants, this very high titer plasma is still available. We're back doing exercise studies.

01:44:06.720 We're back writing papers about exercise and doing our regular physiology. I think this

01:44:11.320 antibody therapies really took a bite out of me. It's like what Jim Bowden said, the great pitcher,

01:44:16.380 you know, you spend your life gripping the ball and thinking about your grip on the ball. And in

01:44:20.620 reality, it was the other way around. The ball had a grip on you. So, you know, I've been thinking a

01:44:24.420 lot about antibodies and maybe antibodies have been thinking about me because it's really hard to

01:44:28.320 stop thinking about it because it's so interesting. And we get reports back to us from not famous

01:44:34.880 patients that are very similar to what we've heard of Mr. Bridges. So we're quite excited to pursue

01:44:38.820 these solutions for our immune suppressed patients. When I started medical school in 1982, those sorts

01:44:44.940 of patients, their life expectancy was quite low. Now our patients with heme malignancy, multiple

01:44:49.900 myeloma, lymphoma, leukemias, a lot of those people live a long, long time.

01:44:55.120 How long after a person is infected and recovers from infection, are they a suitable plasma donor?

01:45:00.020 Within about two to three weeks.

01:45:02.260 When does that window close?

01:45:03.580 It goes on for three or four months, you know, probably up to six months. And it would probably

01:45:07.800 reopen if they got boosted, that sort of thing.

01:45:10.280 You only get sufficient antibodies from people who have had the actual infection,

01:45:13.440 not from people who just go get a booster?

01:45:15.520 Initially, because there were no vaccines, we only had people that had the normal infection.

01:45:19.920 Since the vaccines have become widely available in the last almost 18 months now or 15, 16 months,

01:45:25.480 we've now been able to get people who've had both. The people that have had both are really

01:45:29.060 super donors. And we can work with those people to come back in and get multiple units.

01:45:34.440 We collect our own blood at Mayo. We have a terrific blood bank here locally, but

01:45:37.800 they're using it at Hopkins, they're using it at Harvard, using it at Einstein, a lot of other big

01:45:41.800 places. We're working with the societies, the Food and Drug Administration and others like the

01:45:46.540 Lymphoma or Leukemia and Lymphoma Society, the CLL Group, Infectious Disease or, excuse me,

01:45:52.660 Immune Deficiency Foundation to make sure that we have this available for those sorts of patients.

01:45:57.640 They're doing this at scale in France to about 50 patients a week, which would be about 300 a week

01:46:02.800 in the US if you account for population differences. So that's one of the things we're quite interested

01:46:08.320 in. This is something people can donate. It's a way for people to give back.

01:46:12.000 Are you able to find sufficient donors? Are there enough donors that are aware?

01:46:15.400 Again, because there's so many people who've been both infected and broken through. There's always

01:46:19.640 logistical issues in terms of getting a person to the blood collecting center, getting it here,

01:46:24.080 getting it there. But availability should be pretty high.

01:46:27.700 And with plasma, do you still have to do a type and cross?

01:46:30.740 Got to still be typed and crossed and people are, they have to be eligible to otherwise donate blood.

01:46:35.640 But during the peak of plasma use prior to the vaccines and prior to the monofunals,

01:46:40.420 20, 30, 40,000 units a week were being used in the country. And in the weeks when more plasma was

01:46:46.180 being used, the death rate two weeks later was lower. So there's a pretty nice correlation between it.

01:46:51.080 But again, I think we've talked about training. We've talked a little bit about coaching. We've

01:46:56.320 talked about participation in support and so forth. But I think one of the things that really

01:47:00.900 helped me work with the government and work with our team, instead of do a 5,000-person

01:47:05.480 demonstration project, do really a treatment registry and over 100,000 patients, was the organizational

01:47:11.480 skills I learned from my coaches. And I used to joke with higher-ups in the Food and Drug

01:47:15.940 Administration. They'd say, well, how did you do that? I'd say, I'm a recovering physical educator.

01:47:19.560 And that was always good for laughter in at least a few dark hours.

01:47:24.020 Last question, Mike. Given your longstanding history in athletics, both personally and

01:47:29.380 professionally, are you optimistic or pessimistic about the future of Americans based on the

01:47:35.500 level of physical activity that we see?

01:47:38.120 We need to do something. We need to do something. And I think it really reflects our society in

01:47:45.320 general. I think that you have, for lack of a better word, upper middle class kids who have

01:47:50.180 access to superb coaching, to superb facilities, and to programmatic things. I think we've got a

01:47:58.040 tremendous problem with play and unstructured play. Things that when I was growing up in the 60s and

01:48:04.400 70s that were done through the park district and the school district, I think a lot of those

01:48:08.380 opportunities have fallen by the wayside. The kids who were college athletes used to come back and have

01:48:13.600 open gym all over Tucson when I was a kid. There's no open gym at the high schools in Rochester,

01:48:18.720 Minnesota, a rich community in the summer. And the advantage of open gym was, hey, you got people

01:48:24.440 off the street and they were doing things. And the police knew where we were, which they're always

01:48:28.880 very pleased about. If they know that all the high energy boys are in one place, it makes their life a

01:48:34.220 little easier as well. Yeah, I think it's a real problem. So I think we'll have these incredible

01:48:37.980 performances by the kids who have access. But I think that what we're doing in the rest of the

01:48:44.220 world is problematic. I guess if I could do anything, I'd start a national open gym movement,

01:48:50.720 winter, summer, whatever, because we have a lot of nice facilities that are used just a limited

01:48:54.200 number of time per day. Could you imagine if you were a czar and you could sort of do anything and

01:48:58.620 you just said, no matter what your lot is in life, if you're a school child, if you're a person who

01:49:03.760 works in an office, if you're a person who works in, we somehow rearrange the day such that every

01:49:08.620 person has a mandatory one hour activity. You could make it exercise. You can go to the gym for an

01:49:14.880 hour, but it could also be, look, at a minimum, you got to go out and walk. Well, you know, it's

01:49:19.640 interesting you mentioned that because in our department with remote work and so forth, this

01:49:24.680 has broken down a little bit, but we had a number of secretaries. They were all women, middle-aged

01:49:29.300 women. And we have this huge, deep bunker system with the bowels of the hospital with these huge 1.00

01:49:35.320 hallways. And it's about a mile around the place. And these folks would go down and walk at lunch.

01:49:40.120 They'd bring their tennis shoes to work. They would meet up with their pals and go do 30, 40 minutes

01:49:45.260 a day of laps at lunchtime with the secretaries all over the hospital. And it was, I think, terrific

01:49:51.300 for them. I think it was a social event for them. And I think that they solved a lot of problems

01:49:56.660 too. And they actually made them way more productive. As I said, at the outset, I've

01:50:00.540 enjoyed reading your papers for more than two decades and I'll continue to do so. And it's

01:50:04.980 been great to chat and hopefully we can meet in person at some point and do a workout together.

01:50:09.480 Yeah. I look forward to it. Thank you for listening to this week's episode of The Drive.

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01:52:31.000 I'll see you next time.

The Peter Attia Drive - August 08, 2022

#217 ‒ Exercise, VO2 max, and longevity ｜ Mike Joyner, M.D.

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