The Peter Attia Drive - #134 - James O'Keefe, M.D.： Preventing cardiovascular disease and the risk of too much exercise.

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

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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. My guest this week is Dr. James O'Keefe. James is a cardiologist and

00:00:56.260 medical director of the Charles and Barbara Dubok Cardio Health and Wellness Center at St. Luke's

00:01:02.340 Mid-American Heart Institute, an enormous practice of more than 60 cardiologists in the middle of this

00:01:09.800 lovely country. He is also a professor of medicine at the University of Missouri, Kansas City.

00:01:16.080 James has authored best-selling cardiovascular books for health professionals, including the

00:01:20.340 Complete Guide to EKGs, Dyslipidemia Essentials, and Diabetes Essentials. James has also co-authored

00:01:28.060 with his wife, Joan, the best-selling consumer health book, The Forever Young Diet and Lifestyle.

00:01:33.680 He is actively involved in patient care and research and has published numerous peer-reviewed

00:01:39.480 articles, which honestly, I feel like I'm reading at least one every couple of weeks.

00:01:45.500 I came across James for the first time about nine or 10 years ago when I heard him speak at a

00:01:50.400 conference. And frankly, what he had to talk about just threw me back on my heels. And since that

00:01:56.060 time, of course, we've become friends and James is in many ways a mentor to me with all things that

00:02:01.620 pertain to preventative cardiology. In this episode, we talk about a lot of things, starting with his

00:02:08.160 background and how he made the pivot from going into interventional cardiology to now this much

00:02:14.800 broader area of preventative cardiology. We get into some really detailed, but very accessible

00:02:20.640 physiology of what the heart does, how it works, and therefore how it's susceptible to disease.

00:02:26.180 And then we kind of launch into some of the things I wanted to get to. I wanted to talk about the

00:02:31.060 impact of exercise on the heart, both positive and negative. We go into that in exceptional detail.

00:02:36.080 We get into the role of nutrition and specific nutrients, such as sodium, magnesium, et cetera.

00:02:42.720 And then we round the discussion out with a sort of tour de force discussion of many of the

00:02:49.980 pharmacologic agents that some of you have probably heard of. And frankly, even, you know, this discussion

00:02:56.440 taught me quite a bit and actually invigorated my knowledge for this space. So I always enjoy

00:03:02.360 talking with James and I suspect you will all enjoy this episode very much. So without further delay,

00:03:08.280 please enjoy my conversation with Dr. James O'Keefe.

00:03:16.340 James, thanks so much for sitting down with me today, albeit not in the same physical location,

00:03:21.960 which is always a shame. The last time we were in the same location, you swung by my office in New

00:03:28.120 York. I remember it was probably about three years ago and you were kind enough to bring a recent

00:03:33.200 manuscript you'd just published about the impact of exercise on heart disease. And we had a lovely

00:03:38.580 discussion. I don't think we had the time for a meal that day because it was an impromptu visit,

00:03:43.580 but I never imagined it would be almost three years before we'd be doing our podcast, which is

00:03:49.460 something that from the moment I started a podcast, I knew I wanted to sit down and talk with you.

00:03:53.620 You're also just an incredibly gracious guy who's always sending me stuff. And so I consider you one of

00:04:00.400 those people as my sort of constant educators. So this is going to be an exciting episode because

00:04:06.040 I'm going to be learning a lot. And I know that anybody who cares about heart disease is going

00:04:10.080 to be learning a lot. And I don't know how you can not care about heart disease if you care about

00:04:13.620 longevity. Yeah, it's the heart of the matter for sure. And yeah, I think we all instinctively

00:04:19.560 understand how important the heart is to our health. And I might say in the spirit of educating each

00:04:25.760 other. I love your podcast. I think it is easily my favorite podcast. I love the way you dig down

00:04:32.580 into the science and really get to the heart of the matter without overhyping things. And I just think

00:04:38.280 you're doing a wonderful public service for improving the health of the population. And the

00:04:42.980 other thing I'm really impressed at because a lot of my fellows in residence and kids will talk to me

00:04:48.800 about what they heard on Peter Atiyah. So your audience is particularly, if I might say,

00:04:55.080 tuned in, intelligentsia, interested in health and well-being. And I think you have really curated

00:05:02.640 a remarkable audience. Oh, thank you for that. You and I first met probably 11 years ago, I think.

00:05:11.600 I heard you speaking at a conference and it kind of blew my mind. You won't remember this

00:05:18.020 because it's obviously a topic you've been speaking about a lot. But as the listener,

00:05:23.040 when it's the first time I heard about it, it was kind of a gut punch. So it was probably 2011.

00:05:30.040 And at that time, I was still a wannabe professional athlete. So even though I was into my late 30s,

00:05:38.080 I still pretended that I was a professional something or other swimmer, cyclist, incredibly

00:05:45.780 high volumes of training, incredible intensity of training. I actually did the math for somebody

00:05:52.420 yesterday. And I think I was probably on my bike at least, I don't know, 20 to 23 hours a week

00:05:59.740 with a third of that being at or above threshold. And you presented data basically suggesting

00:06:07.740 that that was harmful, potentially, and that I may have actually gone too far. And I may have

00:06:13.740 actually set myself up for cardiac injury later in life. So with that as a teaser, I now want to

00:06:20.820 take a step way back and talk about your journey to that among many other topics that interest you.

00:06:29.260 You trained as a cardiologist. And just for people who don't understand what that means,

00:06:32.660 that means after medical school, you went and did internal medicine. And after internal medicine,

00:06:37.040 you then train in cardiology. And then you went one step further and said, look, I want to do

00:06:41.140 interventional cardiology. Can you tell people what interventional cardiology is?

00:06:45.040 Yeah. So that's using procedures to fix the heart, whether it's putting stents in the

00:06:50.200 coronary arteries or putting in pacemakers. These days, it's expanded to fixing the valves. It's just

00:06:56.500 the technology is just absolutely spectacular these days. We can put in valves. It's become our

00:07:03.400 default way of replacing a valve now is through the artery. So it's a really cool field. At the time,

00:07:12.140 I went, I trained at the Mayo Clinic for internal medicine and cardiology, and then went down to Kansas

00:07:17.620 City at the Mid-America Heart Institute in 1988 to work with Jeffrey Hartzler, who was the world's

00:07:23.700 expert in interventional cardiology. He invented infarct angioplasty. That is somebody who's having a heart

00:07:28.840 attack. He had the sort of chutzpah to, you know, go in, do an angiogram, figure out which vessel was

00:07:35.520 blocked, open it up with a balloon, and suddenly the pain goes away. At the time, it was radical.

00:07:41.260 This is 1980. And he took a lot of heat for that nationally at the meetings. But it turned out,

00:07:46.400 you know, to be a game changing therapy announced that it's the standard across across the world for,

00:07:51.580 you know, for treating angioplasty. So I went there and worked with him and started off my career. And

00:07:58.340 maybe I'll back up saying, you know, I'm like you, I love exercise. It's how I calm myself down,

00:08:04.440 turn myself up, whatever. I mean, it's just always, my kids say, it's how I've been self-medicating my

00:08:10.800 hyperactivity all my life. And there's probably some truth to that. And it turns out that exercise,

00:08:15.000 it's good for ADHD. Never had trouble focusing, but certainly exercise since I was a little kid is just,

00:08:21.580 my mother used to, her mantra to us was up in the prairie up in Northern North Dakota near Canada.

00:08:28.080 She said, you kids go outside and play, go to school, play with your friends outside. And so

00:08:32.800 that was kind of what I did growing up. And I got into basketball and running cross country in high

00:08:38.200 school when I was just fascinated by the heart. So I figured out I wanted to be a cardiologist when I

00:08:42.480 was 13 or 14, just because I was fascinated with the heart. So back to, you know, through my

00:08:48.720 cardiology training and then doing interventional cardiology. And I did it for about a year or

00:08:53.340 two. And then I realized this back in the night, then we're only doing balloon angioposti. So we

00:08:58.500 balloon these dial, you know, dilate these, these vessels up in elective people. We're having angina

00:09:04.640 and, and then they'd be back in six months or a year with more blockages. And it just don't, I mean,

00:09:10.140 this is not the ideal way to treat coronary disease. This is a systemic disease. It's highly

00:09:16.100 modifiable. We just need to, you know, focus, double down on prevention. And this was just

00:09:21.700 when, when, you know, prevention was blossoming, you know, statins came along in 86 and, you

00:09:27.580 know, we're, you know, the, the beta blockers and, and now, I mean, it's discontinued to blossom

00:09:32.660 so that coronary disease these days, even though it's the leading killer in America, should be

00:09:37.920 an entirely preventable medically managed disease. Unless you have an MI, you don't need to be going

00:09:45.180 in having procedures, stents and electively, you know, we have, we have the tools. And so

00:09:50.620 it's also just the more enlightened approach. I mean, it doesn't pay well, you know, you don't

00:09:56.020 get paid for prevention, but it is the logical way to approach disease, whether you're a physician

00:10:01.360 or just a person out there who's trying to live a happy, long, fully functional life. I mean, you want

00:10:09.120 to be thinking proactively and it is so effective. We know what works now, but you know, we just have

00:10:14.940 to kind of get people's attention and get them to change their habits lots of times.

00:10:19.820 There's a lot in there, James. So let's kind of go back and hash some of it out. So the first thing

00:10:25.100 you noted was that in its earliest renditions as a specialty, interventional cardiology basically had

00:10:32.760 one tool, which was balloon angioplasty. And so, as you explained, you're putting a very small

00:10:38.720 catheter. Can you tell somebody how large a coronary artery is just to give them some scale? So let's

00:10:44.240 take the left main artery coming right off the aorta, right before it bifurcates into the LAD and

00:10:50.900 the CERC, right at that Widowmaker location, which is named appropriately. How many millimeters is that

00:10:56.820 in a normal, healthy 40 or 50 year old? So that's typically about four millimeters,

00:11:02.660 four or five millimeters in the left main coronary, you know, so not quite half a centimeter, which is

00:11:08.180 a third of an inch. Yeah. So we're talking tiny, tiny little, little, little things. Yeah. It's

00:11:14.080 even smaller than that. It's, it's, it's probably even because an inch is 25.4 millimeters for context.

00:11:21.820 So it's a four is obviously less than a quarter of that. You put a little catheter that's obviously

00:11:27.720 smaller than that into said vessel. And that catheter is complicated enough in that it has a

00:11:33.740 built-in balloon that the operator outside the body can control with a syringe by inflating it or

00:11:41.400 deflating it as needed with saline. So it's a really brute force method, isn't it? To sort of force

00:11:48.560 open something that's narrowing. And of course, at the time you weren't leaving anything behind.

00:11:53.380 So the best you could do was get in there, inject saline back and forth, basically use the hydraulic

00:12:00.100 pressure of that to try to force open what was going on. And then you, you left now years later,

00:12:06.760 obviously interventional cardiologists could leave behind something called stents. So little flexible

00:12:12.400 metallic things that would spring open and stay open. And then there's been an entire evolution of

00:12:18.240 that. So folks who are interested, I had a great discussion on this topic with Ethan Weiss.

00:12:22.700 If you're interested, check that podcast out. I don't recall which episode number it was,

00:12:26.620 but if you just search Ethan Weiss's name, it'll, it'll come up. And we go through the history of

00:12:32.300 this a little bit, but more importantly, something you alluded to, which is kind of what the literature

00:12:37.980 tells us about it, which is outside of a few settings, one of them being someone who is actively

00:12:44.600 having a heart attack. Even today, it's not clear there's an overwhelming benefit to putting these

00:12:51.980 stents in people. There's certainly a lot of economic benefit to certain parties, but there's

00:12:58.540 not an enormous clinical benefit outside of acute MI and we can bifurcate into which types of MI,

00:13:05.860 et cetera. But for someone who shows up asymptomatically with a blockage, I don't think there's a single

00:13:13.380 shred of benefit unless something has changed in the literature in the last few months that I was

00:13:17.140 unaware of. Is that still true? That's absolutely true. You know, we think of this and it's very

00:13:22.440 logical, which is why it's been one of the many reasons why this has been so difficult to extinguish

00:13:27.580 this flawed paradigm, that this is a plumbing issue. You have blockages in your arteries. Well,

00:13:34.020 duh, you get rid of the clog. That's that simple. So we've been working on that flawed paradigm for

00:13:41.780 40 years now. And you're right. As logical as that is, it doesn't really turn out to be true.

00:13:49.120 If you have an acute coronary syndrome, the way to think about atherosclerosis is kind of like the

00:13:55.200 zits we get when we're teenagers. And we get these pustules filled with oxidized triglycerides and LDL

00:14:02.740 cholesterol. And then they attract the monocytes and the macrophages that elute these inflammatory

00:14:08.800 markers and they thin out the collagen overlying the zit and it ruptures and, you know, and it drains

00:14:14.320 and heals. If it's a particularly bad zit, you end up with an acne scar for the rest of your life.

00:14:20.520 That same thing happens in your arteries underneath the skin of the artery, the inside skin, which is

00:14:26.060 the endothelium. You form these zits, these pustules filled with nasty, yellowish and flame. And

00:14:33.260 they get hot, they rupture. And instead of just draining, they attract thrombi because they think

00:14:38.520 there's a rent hole in the vessel. So a thrombus forms, platelets and fibrinogen. And over time,

00:14:46.100 you know, it heals if you're lucky enough. And mostly, most of the time you are, this happens

00:14:49.420 time and time again through decades before it gets to the point where one ruptures and then completely

00:14:54.620 closes it off. But in the meanwhile, every time you get one of those inflating zits that ruptures,

00:15:00.200 you get the growth factor, stimulate the growth of the smooth muscle and the collagen. And if it's a

00:15:06.860 really bad zit, you know, eventually you'll calcify. And those are fossil evidence of previous

00:15:12.560 badly inflamed zits, if you will. So this is like really everyday common stuff, but we know how to

00:15:20.960 prevent it. But going in with a balloon and addressing one little area, and by the way, tearing it up even

00:15:26.880 worse. It works if you're having a heart attack. But most of the times we can, we can regress those

00:15:32.200 plaques, we can melt the inflammation out of there. With a lot of things we can talk about diet and

00:15:37.760 lifestyle and exercise, keeping the lipids down and triglycerides down. And we can't make the acne

00:15:43.720 scars go away. They're there forever once you have those calcium deposits. But we can pretty much make

00:15:49.280 the risk go away. And that's why prevention is just so effective and so instrumental.

00:15:56.200 Well, again, I think you said a lot there. And I want to go back because, first of all,

00:16:01.140 I love that analogy. I've never thought of using acne as an analogy. And I think that's actually a

00:16:05.260 more accessible analogy than the ones that I use. So I think with everybody listening to this,

00:16:10.360 I'm going to declare that I'm going to start plagiarizing that. I hope you don't mind.

00:16:13.480 What I find interesting, and I think it's important for patients to understand this,

00:16:17.940 is the complicated biology of both the oxidative piece, the inflammatory piece,

00:16:25.180 and how they feed off each other. And it is a bit of an irony, isn't it? That the body is actually

00:16:30.780 trying to repair something. The immune cells, when those monocytes get recruited to the site of

00:16:38.340 endothelial injury, and obviously when they translocate through the endothelium and become

00:16:43.080 macrophages and start doing everything that you just described, which leads to this creation of

00:16:48.260 thrombus, we would normally welcome that response elsewhere in our body, right? If you were out in

00:16:54.700 the field and you got cut, that's exactly what you would want to happen. You would want the immune

00:17:00.460 cells to show up there to make sure there are no bacteria. And then you would want those thrombo

00:17:06.100 cells to come and prevent you from bleeding. And so the problem is all of that stuff is happening in

00:17:12.440 an area where you don't have a lot of real estate. You've got a few millimeters. And that's why it

00:17:17.920 can obviously lead to this enormous problem. The other thing you said that I think is, it just can't

00:17:22.860 be overstated, is the understanding of what calcification means in that context. I had a

00:17:29.340 patient I saw this week who, after some hesitation, finally agreed to have a calcium scan. He had very

00:17:38.140 elevated lipids for a number of years, but they seemed to elevate more in the previous few years.

00:17:43.600 He had been quite resistant to any medical management of that. And frankly, his other factors

00:17:50.880 are really good. So this is a guy who eats very well, who exercises very well, is metabolically

00:17:57.480 very healthy. So when he got the calcium score, you know, it was about a hundred and change,

00:18:03.080 placing him between about the 75th and 90th percentile for age located in three vessels.

00:18:09.420 He was visibly alarmed, right? He said, this is really bad. And, you know, the stenosis in each

00:18:15.280 of these by calcification were, you know, in the ballpark of 30 to 50%. And, and what I tried,

00:18:21.000 and I don't know if I explained it successfully enough to him was look, the 30 to 50% stenosis you

00:18:27.920 have in that vessel is not the issue. That's a huge warning sign of what has been going on over

00:18:34.800 the past decade. It's telling us that now is the time to act and add other agents to our toolkit for

00:18:42.460 how we're going to prevent myocardial death. The analogy I use is it's like having bars on the window

00:18:49.540 of a home. You know, it doesn't tell you that there's a break-in that's about to happen. It tells

00:18:56.460 you that you live in a very bad neighborhood and there's probably a break-in that took place at

00:18:59.720 some point. Yeah. It's a great way to put it. And also I'm glad that, and I know from our previous

00:19:05.780 conversations that you're a fan of the, of the calcium score, we call it a cardio scan. We charge

00:19:11.180 $50 for it. It's, we use modern CT, high speed CT scans that give these really great pictures of the

00:19:17.960 coronaries with a minimal dose of radiation. So men over age 40, women over age 60, I call it like the

00:19:25.920 mammogram for the heart. I mean, everybody should have one really, because you can have a lot of

00:19:30.580 risk factors for like, say lung cancer. You might be a smoker and a family history and this, that,

00:19:34.740 the next thing. But if we do a scan and see that you're growing a tumor, that's a whole different

00:19:41.240 deal. And that's the way this is. As you point out, there's a lot of people who have high cholesterol

00:19:47.200 and high blood pressure, bad family history, just a frightening array of risk factors. You do a

00:19:53.220 calcium score on them and it's zero. And you say, well, you've gotten through 53 years of life

00:19:57.660 without making any hard plaque. So we're not going to like, we maybe don't need to use a statin on you.

00:20:04.220 Maybe we don't, maybe we can tolerate. And it seems like you're doing fine. On the other hand,

00:20:08.160 there's a lot of people who have relatively minor risk factors start growing plaque. And,

00:20:12.460 and let's be clear, your coronaries should be soft and supple and smooth. Like they were like,

00:20:19.120 when you're a baby, when you're a teenager, there's no calcium in the coronaries normally.

00:20:23.540 And you see people, I think the record I've seen is 13,500 per calcium score. I mean,

00:20:28.940 I often show the residents, like we put the Hounsfield area of interest over the left main

00:20:34.160 of the LAD and it'll be 800, 900. Then you go to their spine and it's 600, 700. Their arteries are

00:20:41.740 more bony than their bones. That's not a good thing.

00:20:45.440 What is the youngest person, James, that you've seen a legitimate speck of calcium in? So something

00:20:51.540 that's not an artifact of a score of one or something, but where there's actual calcification.

00:20:56.540 Yeah. Late teens, but that's really unusual. In the twenties, you start seeing it. And I might say

00:21:01.780 that family history, when people come in, like, like the patients you described, they come in and say,

00:21:06.400 why do I have this? I'm doing everything right. They said, well, you probably have a bad family

00:21:10.520 history, right? Yeah. Yeah. I just said, well, you know, if you weren't doing everything right,

00:21:14.500 if you were a smoker, you'd probably already have had a heart attack, you know? So some of this is

00:21:18.720 non-modifiable, but more and more, I mean, this is a highly modifiable process.

00:21:24.340 Gosh, I almost don't know where to start, but I now feel like I want to start talking about some

00:21:28.520 of the exercise stuff. So let's, I want to come back to cardiovascular disease prevention,

00:21:32.520 because there's so much I want to talk with you about with respect to glycemic control,

00:21:37.160 hyperinsulinemia, other agents that we should be thinking about beyond just lipid lowering agents.

00:21:44.800 And we can dip into that, but I want to talk specifically about one of my favorite classes

00:21:50.240 of drugs, SGLT2 inhibitors. But before we do that, let's go back to circa 2011. James O'Keefe

00:21:57.620 is up on stage and he puts this graph up of a J shaped mortality curve or of exercise. Can you,

00:22:05.380 and by the way, at this point, Peter Atiyah sitting in the audience has probably just finished a four

00:22:09.360 hour bike ride and he's proud of the fact that he kept his heart rate above 172 for half of that

00:22:15.800 time. Can you walk people through basically, not that you remember that exact talk, but basically

00:22:22.680 the thesis? It's a reverse J curve actually, because if exercise were a drug, it would be the best drug

00:22:33.220 we have for preventing heart disease. I mean, for that matter, for preventing dementia, preventing

00:22:38.860 osteoporosis, depression, diabetes, obesity. I mean, it is a wonder drug, if it were a drug.

00:22:45.200 But like with any drug, you got to get the dose right. Say you're using Carvedilol, one of my

00:22:50.220 favorite drugs, and you give somebody who has a fib or recent infarct or high blood pressure,

00:22:56.480 you give them Carvedilol, but it's one milligram. You don't get any benefit, right? On the other hand,

00:23:03.760 you give them, you give them 120 milligrams twice, twice a day. So if you give them a hundred

00:23:12.700 milligrams twice a day of Carvedilol, it's a disaster. I mean, their blood pressure is going

00:23:16.920 to be low. They'll feel terrible. I mean, they'd have a hard time getting up off the couch.

00:23:20.820 Exactly. Right. So it's kind of the same thing with exercise. And amazingly, the dose of exercise

00:23:27.520 to get benefit is really small. I mean, most 50% of Americans do no exercise. If they just got off

00:23:34.720 the couch and went for a walk, a brisk walk, 15 minutes a day, they would get like a 30% reduction

00:23:40.740 in serious cardiovascular disease, 15 minutes a day. Now, ideally, we, you know, we say 150 minutes a

00:23:47.000 week is sort of a lower limit benefit. But the point is that early steep limb of the, of the

00:23:54.560 survival versus exercise dose falls steeply. Your benefit goes down 30, 40, 50%. But then for the last

00:24:04.460 uptick, the people doing the most extreme doses of exercise, you start to lose some benefit. And it's

00:24:10.300 probably upwards of a third of the benefit. So people argue, well, I mean, no sense scaring people

00:24:16.360 off of exercise. I mean, it's just sort of an encouragement to not exercise, knowing that

00:24:22.520 if you overdo it, you could make yourself worse. And, and, and to be clear, it's only like 2.5%

00:24:29.040 of Americans are probably overdoing exercise versus at least 50% who are underdoing exercise.

00:24:34.680 But still, it's a bit like, just because 50 to well, 70% of Americans are overweight or obese.

00:24:40.400 And it's like saying, well, we don't really want to talk about the dangers of anorexia,

00:24:44.080 because then, you know, we're kind of, we'll sort of discourage people from not eating as

00:24:49.080 much. I mean, it's the mirror image of this. But the point is, you can't overdo exercise. And,

00:24:54.700 you know, it might be interesting. As just an example, I know that you swam the Catalina

00:24:59.580 channel, like 15 years ago, right?

00:25:03.240 Yeah.

00:25:04.520 And I mean, that was pretty amazing feat. So when you're sitting here talking to me,

00:25:09.080 and your heart is beating probably about 45 beats a minute, and pumping out about five liters a

00:25:16.500 minute of blood, when you're doing high intensity intervals, or when you're swimming across the

00:25:23.680 Catalina channel, and, you know, I mean, a fast rate, I mean, you did that 20 miles in like 12 and

00:25:28.800 a half, I mean, 10, 10 and a half hours.

00:25:30.340 So actually, I think cycling is a is an even more amazing place to show that because actually,

00:25:36.560 for the channel, I would probably a there's something about swimming where you're horizontal,

00:25:42.940 I think your heart rate for very short distances can obviously climb like crazy. But I find on the

00:25:49.660 bike, you would get the highest heart rate. So so for me, the maximum area under the curve heart rate

00:25:55.920 was a one hour time trial. So so like a 40 kilometer time trial would be absolutely maximum

00:26:04.660 heart rate.

00:26:06.640 How fast would it be going?

00:26:08.440 I have a slow heart rate all round. So my max, my my heart rate would be about 172 for for that type

00:26:17.000 of a race.

00:26:17.800 For an hour. Well, take it less than an hour, probably.

00:26:20.800 Yes, exactly. It would take about 54, 56 minutes, 55 minutes, maybe.

00:26:24.960 No, but that's a perfect example, because it's not only high heart rate, but it's exercising under

00:26:30.600 a load. It's like rowing, you know, this is your you're you're using big muscles, you know,

00:26:35.320 your blood pressure is also probably 200, your systolic pressure, your pulmonary pressure is

00:26:39.980 probably 80, 60, 70, 80.

00:26:42.800 Let's give people some metrics of normal. So for obviously, doctors listening to this will know what

00:26:46.660 we're talking about. But let's take a step back. So let's say my blood pressure is I've pretty

00:26:50.580 normal blood pressure. I'm probably about a 115 over 75 is my normal blood pressure. Can you tell

00:26:57.840 people what that means, by the way? What do those numbers mean when you have blood pressure checked?

00:27:02.380 You know, this is just the pressure that is exerted to pump these five liters of blood around your

00:27:08.100 around your circuit every minute. It takes that pressure to you know, that's the normal pressure

00:27:13.340 to just kind of get that blood squirting around there. And then it comes back at only like two or three

00:27:18.860 or four millimeters of mercury up from the legs. And and that's that's a more difficult physics

00:27:23.860 problem, right? Because you're over overcoming gravity at low pressures, which is why it's good

00:27:28.860 not to be obese. It's good to be exercising because those muscles milk the blood back through the veins

00:27:33.940 through the through the valves up to the heart. And those two numbers, of course, referred to as

00:27:39.040 systolic and diastolic, the systolic is when the heart is squeezing. So during the squeeze of the left

00:27:45.040 ventricle, the pressure at the tip of the basically in the aorta is 115 millimeters of mercury. Now

00:27:52.040 anybody who's ever mucked around with a pressure transducer will actually be surprised at how much

00:27:57.500 pressure that is. That's a non-trivial amount of pressure. If you've had the luxury of operating on

00:28:02.920 people, you know what 115, even a normal 115 millimeters of mercury is that'll squirt across the

00:28:08.440 room. Across the room. But the 75 refers to the relaxation phase of the heart. It says even when

00:28:15.620 the heart is relaxed and in the what we call diastolic phase receiving its blood supply, there's

00:28:22.780 still quite a bit of pressure in there. 75 millimeters of mercury in my case. Because your

00:28:27.260 vessels are nice and elastic. So, you know, as it receives the bolus of blood, everything expands.

00:28:32.900 And then when the aortic valve shuts, then those vessels, they rebound a little bit and they keep the

00:28:38.320 take this sort of pulsatile bolus flow and turn it to more of a laminar, less bolus flow. So that

00:28:44.740 elasticity of the vessels are super important. Now you talked about my pulmonary pressures.

00:28:50.340 What are my pulmonary pressures sitting here right now? And I'll confess to you, I have no pulmonary

00:28:55.820 disease, though I've never had a swan-gans catheter placed in me. So what would you assume my pulmonary

00:29:00.340 pressures are? Oh, they'd be low, you know, like 20, 25 over 15, something like that. Nice and low.

00:29:06.960 Okay. So basically that's the same exercise, but now you're in my pulmonary arteries instead of my

00:29:13.240 systemic arteries. Let's just assert that my heart rate's 45 beats per minute. And you said my cardiac

00:29:20.200 output is five liters per minute. So that means every minute my heart sends five liters of blood

00:29:28.340 around my body. So I love that you brought up cardiac output because I think that's the variable most

00:29:36.100 people are sort of failing to appreciate how much that has to improve. So when a weekend warrior like

00:29:43.180 me would try to do his best one hour time trial, or when the best cyclist in the world or the best

00:29:49.740 runner in the world is, you know, doing their most exerted thing, what's the variability or the range

00:29:57.380 in cardiac output that we can see from best in the world to sort of weekend warrior to average

00:30:03.200 conditioned person? Just by way of context, if you look down at your hand and make a fist,

00:30:09.020 that's about how big your heart is. This is an amazing pump. So five quarts a minute, think if

00:30:14.400 you were, you know, squeezing a bowl, five quarts a minute, five liters per minute, yep, five liters per

00:30:19.660 minute, it never stops. And you're a good heart should have about three or 4 billion beats in it

00:30:27.960 without ever stopping. Okay. It's about a billion beats every 30 years, which is for a math geek like

00:30:35.940 you, it's kind of fun to think about, you know, you know, think about designing a lifestyle and

00:30:41.100 exercise program to sort of minimize the number of heartbeats per year. Okay. And it does involve

00:30:45.340 exercise, but it doesn't involve, you know, it doesn't involve Herculean efforts of protracted

00:30:51.060 exercise. All right. But a good athlete like you, an exceptional athlete like you, you go out and do

00:30:57.700 that time trial, that one hour time trial at 175 beats a minute under load for an hour, you're pumping

00:31:05.720 like 30 or 35 liters a minute. Think about that, you know, 10 gallons a minute, you know, like Lance

00:31:15.760 Armstrong and those, you know, the professional cyclists or cross country skiers will get up to

00:31:20.360 40, 40 liters per minute. You mistakenly referred to me as an exceptional athlete, which even at the

00:31:25.580 time I wasn't, but yeah, when you do talk about the exceptional, when you talk about Lance Armstrong

00:31:30.920 riding up Alpe d'Huez in 38 minutes, and it doesn't matter that he was on EPO. It really doesn't change

00:31:38.200 the metrics of this. 40 liters per minute of cardiac output, you know, to put this in perspective,

00:31:45.160 James, I just love this so much because the only times I've ever measured cardiac output are in

00:31:52.360 patients in an ICU. I mean, I can't count the number of times I've put a catheter into somebody's lungs to

00:31:58.940 measure and their heart to measure their cardiac output, but it's always been in the setting of a

00:32:03.940 patient under critical care. And in that setting, it would be routine to see two and three liters of

00:32:11.100 cardiac output per minute. And that's with every drug under the sun used to squeeze their heart. And to

00:32:19.140 think that you and I have the luxury of sitting here without a single drug to increase the contractility

00:32:25.200 of our heart. And we're at five liters per minute. And even a couple of old guys like us could probably go

00:32:29.700 out and exercise and still hit 25 liters per minute, but that the best in the world can hit 40 liters per minute.

00:32:36.000 Now let's do some math to get to that volume flow rate. Really their heart rate isn't making up the

00:32:46.340 whole gap because cardiac output is a product of two variables, the heart rate and the stroke volume.

00:32:53.820 Can you sort of explain how those play together? Well, right. The stroke volume is, you know,

00:32:59.180 your heart's a pump. And so, you know, in between beats it fills. So how big it can accommodate, how

00:33:05.720 much, how much volume it can accommodate with each beat is a, an important factor. And I remember

00:33:10.520 Miguel Indorain had some studies done years ago and his heart was basically twice normal size.

00:33:16.700 So you get the heart rate up, the volume goes up, your arterioles and venules dilate up so that the

00:33:22.920 resistance goes down. And the heart is actually not just a pump, but it like, it rings out the blood.

00:33:28.020 It shortens and twists. And when it's going fast and you're exercising, it's basically

00:33:32.660 sucking blood out of the lungs and the venous system into this and pumping out as fast as it

00:33:38.120 can. I mean, it's just, it's just an elegant, astoundingly well-designed system when it's used

00:33:44.640 right. And, and of course, that's one of the beauties of exercise. You know, you can feel that

00:33:48.640 from the, as you get into shape, you can just feel yourself being more capable of this. And it's just,

00:33:53.320 it's just intoxicating. And it's one of the beauties why people get addicted to exercise.

00:33:57.920 But, but the point is to get back to the underlying concept is that you could imagine

00:34:04.180 when you're going that hard and your blood pressure's up and your pulmonary pressures

00:34:09.660 are up and you're doing 25 liters a minute, the soft pliable chambers in the heart, that's the

00:34:16.520 atria, the right and left atria and the right ventricle, they get distended. They stretch out.

00:34:20.560 Let's pause on that. So people see why James, because if my cardiac output, which is the dot

00:34:27.640 product of heart rate and stroke volume, meaning if one goes up by two fold, the other can go down

00:34:34.560 by half and they'd stay the same. But if the whole thing has to go up by six X and my heart rate's only

00:34:42.200 going up by three X because 45 to one 70 is about three X, you have to bring the other one up by two

00:34:49.440 X. So how do you take up stroke volume that much? Well, part of it is what you just said. You can

00:34:56.280 squeeze harder, you can twist, you can, you can get every last drop out, but there's no getting around

00:35:02.140 what you're just about to explain to people, which is you have to make that chamber a heck of a lot bigger.

00:35:08.280 Right. And, you know, we're designed for this through nature. We're designed to be very active

00:35:13.960 creatures. But, you know, most of the time, if you look at tribes in the wild, they're doing like 16

00:35:19.660 or 18,000 steps a day. But most of that is out of sort of a comfortable walking pace. Lots of times

00:35:25.760 they're carrying things or they might be, they might be lifting, chopping, swimming, you know, whatever,

00:35:32.120 building and occasionally critical times in the hunt or whatever, you know, they might be sprinting.

00:35:38.280 Although the younger members in the tribe would be assigned that task because they're faster

00:35:42.660 runners, but we're not really designed to do what you did when you were doing these, like you still

00:35:49.300 do, you know, do these really long bike rides, the chambers or marathons, ultra marathons, you know,

00:35:55.660 the chambers dilate up and we have enough circulating buffers in our bloodstream because this is like an

00:36:01.980 engine when, you know, like an exercising muscle uses fuel, glucose, fatty acids, ketones to create

00:36:09.800 energy, but it throws off exhaust. And when you're exercising that hard, it throws off a lot of

00:36:15.820 exhaust in the form of free radicals. Okay. We have a lot of circulating buffers in there to basically

00:36:21.480 neutralize those free radicals. But we, we deplete that after 45 to 50 minutes of high intensity

00:36:28.080 exercise and there's good animal studies showing and human studies showing that diastolic function

00:36:33.980 improves for the first 30 minutes of exercise. And by 50 minutes or 60 minutes, it starts to worsen

00:36:39.680 and the endothelial function will start to worsen too. After you depleted those antioxidants after 45

00:36:45.020 or 50 minutes, you start like searing inside of your vessels, those endothelial sensitive endothelial

00:36:51.480 alignings with high, high free radical levels. And you also start overtaxing the heart muscle.

00:36:58.300 And I'm not saying it's, it's not a big deal, especially when you're young, you know, youth is,

00:37:02.940 you know, when we're young, we're so resilient that you can get away with doing this stuff when you're

00:37:06.960 15 or 20 or 25 or 30 or 35 and maybe even 40 or 45. But after 45, it starts more likely taking a toll.

00:37:14.980 You start seeing, you know, troponins will rise and, and, and, and NT pro and BP will rise after

00:37:20.880 really, really strong efforts. Like, like a marathon. Tell folks what those markers mean,

00:37:25.980 because anybody who's been to an ER with chest pain will know what a troponin is, or has taken

00:37:31.360 their grandmother into the ER with heart failure. But for most people, they might not know what those

00:37:35.840 are and why seeing an elevation in those post exercise should cause us to pause.

00:37:41.000 Yeah. So troponin is one of the proteins that is unique to the heart and it leaks out of the heart

00:37:48.740 and gets into the bloodstream when there's been some heart damage. You know, we usually associate

00:37:53.600 it with, like you say, heart attacks where the artery closes off and the muscle is starved for

00:37:58.340 oxygen and it dies downstream and that, unless there's good collaterals. So that really raises our

00:38:03.980 eyebrows and gets us into action when we see an elevated troponin. But a lot of people, I mean,

00:38:09.780 upwards of half or more people after a marathon will have an elevated troponin. It's just the

00:38:15.020 vest at that high level, 25, 30 liters a minute for two and a half, three, four hours. It starts

00:38:21.220 overstretching the muscles in the atria and the right ventricle particularly, and it leaks into

00:38:26.160 the bloodstream. And again, you know, like I tell people, if you want to run a marathon, fine, you

00:38:30.780 know, run one or two, but don't make it, you know, it's like, like, like climbing Mount Everest.

00:38:34.860 You know, if you want to do that, do it once, but don't do it like three times a year. You know,

00:38:39.820 you could do it, brag about it and all that, but this, you know, you got to move on to healthier

00:38:43.680 forms of exercise because these really, especially after age 40 or 45, really protracted exercise will

00:38:50.620 cause this small little micro damage, like overstretching and tearing because the high levels

00:38:56.280 of catecholamines and high levels of free radicals that are now unbuffered. And so if you're designing,

00:39:02.460 like, I like to talk about training for longevity is very different than training for peak exercise.

00:39:08.260 And a car buff like you can understand that. It's like, if you're going to build a formula one car

00:39:13.420 to go fast, powerful, the most impressive performance machine ever, it's going to look

00:39:18.440 and perform a certain way. And it's good at that, but it's not going to go 500,000 miles.

00:39:23.800 You know, it's built for power and speed and performance. Now, like a car that's going to go 500,000

00:39:29.980 miles. I don't know. It might be a, you know, a Honda Accord that you're driving never more than 70

00:39:34.640 miles an hour and you keep and maintaining it really well. And so the point is that you have to

00:39:39.780 really focus on what your goals are and our goals as an athlete is different than our goals for

00:39:46.700 longevity and health and wellbeing. You know, I love that analogy and I appreciate you using it for

00:39:52.800 me because you know how much I do love cars. In fact, I actually think I made that comment to a

00:39:59.080 patient this week using a formula one car as the reference, because as you pointed out, James,

00:40:05.020 these are cars that are built for each race. Effectively, they'll go through three engines in

00:40:10.620 a season. So everything about that is meant to extract the absolute maximum performance.

00:40:18.620 Again, I want to reiterate what you said. If your goal is to win the Ironman triathlon,

00:40:27.000 nothing we're saying here should pertain to you. We're not going to tell you how to train for that.

00:40:31.840 That is a remarkable feat. I mean, when I think about what it would take to go seven hours in that heat

00:40:40.280 to do what's involved in an Ironman, I can't fathom that. There's never a time in my life when I've

00:40:46.240 even approached the level of raw performance that the winner of Ironman is going to take,

00:40:51.760 or frankly, even somebody who comes in under 10 hours.

00:40:55.260 But swimming the Catalina channel in the dark, you know, in 10 and a half hours, that is also a

00:41:01.500 pretty remarkable feat that's way beyond what a normal person's anywhere capable of doing.

00:41:08.260 Yeah, perhaps. I've never had to do all three at once. So when I was growing up, I was a good runner.

00:41:13.000 Good as a, maybe a stretch. I was a decent, you know, long, long, long distance runner.

00:41:17.800 When I was swimming channels, I could swim for long distances. And then when I could time trial,

00:41:23.260 I could time trial. But there's something about the Ironman or triathletes that can do

00:41:26.920 all of those things simultaneously. That's always impressed me. But my point is you're bringing up

00:41:32.700 the important distinction here, which is at some point, an individual has to decide which master

00:41:37.600 they're serving. Are they serving the performance master or are they serving the longevity master?

00:41:42.520 And I think everybody goes through a difficult transition here. And I see this struggle with

00:41:48.260 many of my patients, especially the former, you know, exceptional athletes, or frankly,

00:41:54.000 not even people who were themselves exceptional athletes, but people who have also become,

00:41:59.880 I don't know how to describe it, but they've found a new sense of purpose through some of their

00:42:04.060 athletic endeavors. And they've done their first marathon and they've thought, oh my God,

00:42:08.840 this is really a great thing to do because there was a purpose, there was a goal, there was a

00:42:12.900 training plan, there was a camaraderie that came through that. I got to do the thing and now I

00:42:18.200 want to do it again and again and again and again.

00:42:20.220 And they've made a lot of friends doing it too. And it's a, it's a, it's a bonding experience and

00:42:24.920 there's a lot good about that. But I'll just interject my, my transitions because I guess I played

00:42:31.620 basketball, you know, competitively in varsity and high school and college. And then

00:42:35.200 for the first two years of college anyway. And then because I felt that that exercise was so

00:42:39.980 important to me, I made this mental note when I stopped playing varsity basketball that I would

00:42:43.900 exercise pretty much every day because I knew it made me happy and healthy. So then I kind of got

00:42:48.940 into running, then triathlons and I did short, you know, like short distance sprint triathlons,

00:42:54.660 but I hammered. I mean, I trained really hard and especially during my thirties up until my mid forties.

00:43:00.040 And I was pretty good, you know, winning like sprint distances, you know, and local races and

00:43:04.600 stuff like that. But it was just the fun of the competition and the friends and all that.

00:43:09.080 But then, then I started noticing when I'd go out and I also in the back of my mind being a

00:43:13.180 cardiologist, you know, sort of thinking, being proud and happy that, you know, that I'm capable

00:43:17.080 of doing this, you know, in my, in middle age. But then I started noticing like when I'd go on

00:43:21.920 really hard rides and do those hard intervals after I have this sort of vague sense of like aching in

00:43:28.100 my chest. And sometimes I feel some, like I'm one of those people, maybe you are too, a lot of people

00:43:32.400 who are athletic. You can feel like if I stop right now and be quiet, I could count my pulse,

00:43:38.560 just, just feeling every heartbeat. And I could feel some ectopies, some PVCs or some PACs or two

00:43:44.780 or three runs in a row of PACs or super ventricular tachycardia. And I thought, you know what,

00:43:50.240 my heart is not happy about this, you know, and, and it disturbed me a little bit. And I kind of

00:43:55.380 checked a cardio scan, I had a little bit of calcium, 21. But then I started to thought about

00:44:00.080 and I thought, you know, this is makes no sense. I mean, I'm thinking that if some exercise is good,

00:44:05.200 and moderate exercise is better, that extreme exercise is the best. There's nothing in biology

00:44:11.320 like that, where the far extreme, it's usually moderation, and especially moderation in the

00:44:17.300 context of what we are evolutionarily designed to do. And what I was doing for a 45 year old was

00:44:22.960 out of bounds with respect to what, you know, my body was expecting. And, and so I started looking

00:44:29.240 into this and talking to some of my friends and colleagues from around my practice and around the

00:44:34.740 world, really, Peter Schnorr in Copenhagen, putting together some databases, and showing that in fact,

00:44:40.540 and this is there in plain sight all the time, by the way, Paffenbarger, one of the godfathers of the

00:44:46.040 exercise movement, in his study in the New England Journal of Medicine, pointing out in these Harvard

00:44:50.860 alums that, that exercise improved longevity, like eight to 10 years. But in the, in the extreme

00:44:56.980 decile, it's just a small group of people, we're doing the most exercise per week actually lost

00:45:03.080 like 38% of the benefit conferred by the less extreme effort. And, and then Ken Cooper, another

00:45:09.440 one of the sort of founding fathers of the modern aerobics movement down in Dallas used to say,

00:45:15.040 if you're running more than 15 miles a week, you're doing it for some other reason besides health.

00:45:19.640 So they recognized, and even Hippocrates 2,500 years ago said, if we could prescribe the right

00:45:26.680 dose of exercise and nutrition, not too little, not too much is the safest way to health. I mean,

00:45:32.760 so this has been there right along that, you know, even back 2,500 years ago, they, they recognized that

00:45:38.360 it's not going to be sedentary, but you can overdo it. You can kill yourself with too much exercise.

00:45:43.860 Let's go back to what you were talking about with respect to PVCs. Explain to folks,

00:45:49.220 what's actually happening with a PVC, because I think this for me became the area when I, where

00:45:57.720 I started to pay attention. Just to be clear, James, it took me three years to fully embrace this

00:46:04.760 message. It was not until 2014 that I finally realized I needed to get into one camp and I

00:46:12.740 couldn't serve two masters and my higher priority was going to be my longevity. And that meant I was

00:46:18.700 not going to do these crushing workouts anymore. My workouts were going to be geared towards what

00:46:25.240 makes me live longer. And the data that I found most convincing were the electrophysiologic data.

00:46:32.900 So it was looking at athletes, the incidence of atrial fibrillation in cyclists and runners who were

00:46:41.660 at or above a certain volume versus normal age matched controls. And yes, that's full of all the

00:46:49.080 same problems and pitfalls that epidemiology was full of. But when the magnitude was so big,

00:46:55.340 it was difficult to ignore. And if I recall, the magnitude was in the ballpark of about seven X.

00:47:00.080 In other words, if you took, you know, retired professional cyclists and you compared them to

00:47:05.600 age matched controls and match them in any way possible, these professional cyclists were seven

00:47:11.180 times more likely to have atrial fibrillation. Does that, is my memory serving me correctly or am I

00:47:16.160 out to lunch on that? No, that's, that's almost spot on. But also I point out that, you know, the heart

00:47:21.760 is very capable of healing itself almost always. And so it's really these high volume athletes,

00:47:29.260 high volume, high intensity athletes who continue to do it. All right. Past, you know, like in the

00:47:34.740 middle age and beyond are the ones I see these people all the time because I've written about

00:47:38.600 this a lot. I see patients all the time come in with AFib and it's like 700% increased incidence

00:47:44.620 of AFib, which is a really common heart arrhythmia where the atrial where the rhythm arises becomes

00:47:51.080 disorganized and chaotic. And so it, it just scoots through the AV node to into the conduction

00:47:56.080 system down in the bottom, working part of the heart rapidly and irregularly. And it's becoming

00:48:02.140 more common all the time in America because it's common among older people, obesity, diabetes,

00:48:08.060 sleep apnea, tall people, too much alcohol can cause it. But one of the causes that we see is in

00:48:13.600 people who are overdoing high intensity exercise. So yeah, you're right on there.

00:48:17.700 I cut you off or rambled too long in my question, but tell people what a PVC is and why,

00:48:23.840 and is that an early warning sign? The high catecholamine levels from protracted exercise

00:48:29.920 and the high oxidative stress and the stretched chamber causes some tearing of the myocardial

00:48:36.380 fibers with protracted exercise. And over time that can cause little micro islands of fibrosis

00:48:42.740 in the myocardial scar tissue. And so if you keep doing this like year after year, decade after decade,

00:48:48.800 you start ending up with this stiff dilated chambers, which then is the electrical milieu

00:48:55.520 that is favorable for creating these rhythm problems. At first things like PVCs, but eventually

00:49:01.860 can lead to VT. But again, an AFib is much more common still, but these are signs that your heart's

00:49:09.100 irritable. Your heart's been irritated by something. And in this case, it's too much exercise.

00:49:14.480 So let's talk about perhaps one of the more sad publicly known examples of that, which you've

00:49:21.840 spoken about publicly, which is the sudden death of Micah True. Tell folks a little bit about who he is

00:49:28.220 and what a remarkable specimen he was and what conclusions you drew from his death.

00:49:34.080 Yeah. So he's sort of the poster boy for the thing, you know, that you'd really kind of, um,

00:49:38.460 an extreme example. So Micah True was a remarkable endurance runner. The book Born to Run was written

00:49:46.500 about him. And he was a kind of a hippie who sort of dropped out of society and decided to just become

00:49:52.360 a runner. He went down to Northern Mexico and, and ran with this tribe that has runners in it,

00:49:59.000 the Tarahumara Indians. And he would run just remarkable distances and became sort of like an example

00:50:05.760 of any of this. He was in his forties or fifties when this happened, but, but he was out for a run

00:50:12.220 and he died suddenly and they did an autopsy. And he found this, you know, dilated, scarred up heart,

00:50:18.460 just what we were describing, you know, the scarring in the atria and the ventricles, especially the right

00:50:22.780 ventricle, interventricular septum. But the point is that he was really fit. He accomplished a lot of

00:50:28.840 really impressive things, but it did take a toll on, on his heart. And now granted he was doing just

00:50:35.200 superhuman volumes. I mean, he would typically run 12 miles a day, as I recall, and lots of times would

00:50:42.000 do these 50 or a hundred mile races through the desert heat and things like that. But yeah, I'm not

00:50:47.580 a big fan of these extreme. And there's more, I have a friend who, who did the, um, seven marathons in

00:50:53.440 seven days on seven continents race. Megan, you know, she's a really, she's a good friend, known

00:50:59.560 her for a long time. She's, she was one of the best triathletes in America when she was doing that 10

00:51:04.500 years ago. And now she's still exercises a lot, although she's kind of cut back on it. But if you

00:51:10.000 measured what's going on with her heart during those times, it's, I mean, it's not pretty. It's like the

00:51:15.200 heart suffers when we really, really overdo it. Of course, all of these data that we look at, the inverted

00:51:21.460 J curve, a lot of the, the Harvard prospective study, even though they're prospective, they're still

00:51:26.100 epidemiologic. A critic of this would say, look, we don't have any randomized data, experimental human

00:51:33.880 randomized data to tell us that the dose curve to exercise is nonlinear. Again, what that means is

00:51:40.300 linear means the more you do, the better you get. You're proposing the more you do, the better you get

00:51:45.660 to a point, and then it actually goes down. Hence the inverted or upside down J. What about animal

00:51:50.780 models? Are there appropriate animal models that can be studied here? If so, what have they shown?

00:51:55.740 Yeah, the animal models, most of them with mice, but a few with dogs have been pretty much consistent

00:52:00.640 with this, that you do see these elevations of troponin acutely. And if you keep, keep them going

00:52:06.620 for months or a year or two, you can see these dilated chambers with the substrate for arrhythmias.

00:52:12.720 And if you look at the epidemiological data in our last paper that we just published,

00:52:17.120 it's called training for longevity, we put all the major 10 big epidemiologic studies and all but

00:52:23.180 two of them showed this very distinct reverse J curve so that you get this deep reduction in

00:52:28.620 mortality that plateaus off in the middle and at the very end, it fish hooks up. It's like diet in

00:52:34.560 that so you're not going to be able to prove it because these are lifelong kind of patterns that

00:52:38.880 emerge and it's impossible to randomize people too. But you know, there's a lot to be said for the

00:52:43.660 end of one. You know, you're paying close attention to your body. I can tell you for me,

00:52:50.000 as a cardiologist, and also just as an athlete and a person, it was very apparent to me that

00:52:55.720 if I didn't change this, it was not good for my heart. And let's just talk for a moment about

00:53:01.900 the best kind of exercise if you just stop talking about volume and intensity, but just talk about

00:53:07.100 like the best kinds of exercise because this this friend of mine, Peter Schnorr and Jacob Marat,

00:53:11.820 he's a brilliant PhD from Denmark, from Copenhagen. Peter Schnorr founded the Copenhagen City Heart

00:53:17.780 Study. This is 10,000 Danes that they enrolled 25 to 40 years ago and focused kind of like the

00:53:24.560 Framingham Study was in America for diet and lifestyle. This was like the Framingham Study for

00:53:30.380 exercise. They sort of collected a lot of data about what people were doing for exercise and then

00:53:37.460 followed him through the decades. And, you know, the people in Copenhagen, I think it's the city in

00:53:42.660 the world that has the largest number of people who bike to work. I mean, it's just it's a flat city.

00:53:47.640 They have these kind of really generous bike lanes. And it's just really fun to watch how people

00:53:53.000 bike to work, but they do a lot of other things. And so they collected data on eight or nine specific

00:53:59.620 sports, including running, swimming, cycling, health club activities, which included treadmill and

00:54:07.740 all the stationary exercise machines with weight that put all that together. And then there was

00:54:13.200 tennis, badminton, soccer, golf, I think were the ones. And so we sat down, we'd done some others

00:54:20.680 analysis, this data showing that it was the moderate dose runners that did the best for longevity

00:54:25.360 during the four decades long follow up of that. But this was a more, this was a different look at

00:54:31.480 it. And so we said, what sport is best for conferring longevity? And so, you know, they did all the

00:54:37.520 multivariable analysis for because, you know, tennis players are different than, than maybe cyclists or

00:54:43.320 whatever, but quantitative how much exercise per week. And maybe you know this data, but, but what do you

00:54:48.760 think? I know it's just shocked me. I went over there to, to finally look at the data and we were sitting

00:54:54.760 on a coffee table one Sunday afternoon, having a glass of wine and talking it over. And he sort of

00:54:59.820 reveals this data to me and I look at it, you know, it's multivariable adjusted data. And I was really

00:55:05.220 like speechless. I was just, it just, I just thought, Oh, what a waste. We spent all this time

00:55:10.000 and this is nonsense. So, so what do you think came out as the least effective way for improving

00:55:15.700 longevity compared to say sedentary population? I've read this, so I'll let you disclose both the

00:55:22.440 best and the worst. Okay. So the worst was health club activities and the best was tennis followed

00:55:29.080 closely by badminton, soccer, golf, and the middle three were like cycling, swimming, running. And

00:55:36.620 that was like three to four years out of life expectancy, health club activities over one and

00:55:40.220 a half year life expectancy added. And, and those social sports, badminton, tennis, golf. I mean,

00:55:47.720 it's easy to imagine soccer, but we're like six to 10 years added life expectancy, multivariable.

00:55:53.520 And I just thought, well, we, it's not even a sense of publishing this, but then I started looking

00:55:57.500 at it and thinking, wait, what if, what if it's not so much about what hammers your body into peak

00:56:03.380 fitness as well as what sort of reduces stress, makes you happy, something you can do lifelong and

00:56:09.380 sort of fosters personal relationships? Because there's a lot of studies in recent decades, one by

00:56:16.160 Julianne Holt Lundstedt that said the single best predictor better than smoking or diabetes or

00:56:22.020 exercise or blood pressure lipids for conferring longevity was strong social support, you know,

00:56:30.040 relationships are the key. And you kind of instinctively would understand that, but then I

00:56:34.320 started thinking, well, you know, particularly for us sort of like emotionally challenged gender,

00:56:39.460 you know, males, it's like we make friends at work, but, and we have our family, but lots of times we

00:56:44.900 bond by playing. And, and when you think about these, the sports that were done playing were the

00:56:53.300 ones that conferred best longevity. And they're also the ones that sort of promote more social

00:56:58.200 activities. So I think, I think we need to change our mind around about what best exercise is not about

00:57:04.580 if you're training for longevity. Yeah. Take it down a couple of notches, but also make sure

00:57:09.080 that you have some play in your life. We played as kids, we need to be playing as adults even more

00:57:15.280 because it's so important, not all for social bonding, for stress relief, for at the depressant.

00:57:20.720 I mean, I just think it's so important. Yeah. I think my reading of that was basically,

00:57:25.820 look, there are a lot of variables that can't be teased out of any multivariate analysis or

00:57:32.760 correction, but a couple of things stuck out to me. One was, I think you're right. I think

00:57:38.200 what tennis and golf, badminton soccer offered that running, cycling and swimming didn't to the

00:57:46.380 same extent on average, not globally, but on average is you got to combine two medicines instead

00:57:52.320 of one. And you know, better than me, that two drugs are often much better than one to control

00:57:57.800 blood pressure. So when you got to combine exercise with social interaction, it does better

00:58:04.240 than just exercise. That's sort of the first thing I take away from that. The second thing I take away

00:58:08.840 from it, frankly, is the challenge of doing any sort of large scale study where you don't have

00:58:13.680 a close ability to understand the intervention. And I'm very fortunate that I have a gym at home,

00:58:19.460 so I don't work out in gyms anymore. But from the days when I used to work out in gyms,

00:58:24.340 I realized that if we were going to treat everybody in that gym as one cohort of everybody

00:58:29.640 who goes to the quote health club, we would glean very little because the difference between what

00:58:36.100 people did in that gym is so enormous that the average of that borders on meaningless, just as

00:58:43.360 the average of what any group of individuals does is effectively meaningless because there is no ability

00:58:49.580 to control for it. So those are the two things that I took from that. Now, I do want to go

00:58:54.160 back to kind of something you said because, look, I think there are going to be a lot of people who

00:58:59.380 listen to this who are going to be exercising more than what you put forth. I think you said earlier

00:59:05.560 something to the effect of, look, 15 miles a week of running is probably adequate. If running is

00:59:11.740 something you enjoy doing, you probably don't need to be running more than 15 miles a week.

00:59:15.780 I'll tell you this right now. My wife runs a hell of a lot more than 15 miles per week. 1.00

00:59:19.800 So here's my argument to her to run less. It's, and I use economic terms called opportunity cost. 0.95

00:59:29.520 It's like, look, Jill, I know you want to run 50 miles a week. And I know if you had all the time

00:59:34.340 in the world, you'd run 50 miles a week, but it comes at the cost of you doing not a single other

00:59:39.800 form of exercise, no strength training, no rowing, no this, no that. So really the argument is,

00:59:47.940 and this was the argument for me in cycling as well, which was look, one, you just, you're tired

00:59:53.780 of spending all this time training when you, you have kids that are getting older and older and you

00:59:57.680 have more kids and it's, there's just a cost to being away from that. But, but it really comes down

01:00:02.880 to how can you be a more balanced athlete for life? So maybe not a better athlete in a very specific

01:00:10.040 sport because cycling is a very specific sport. Running is a very specific sport. If you want to be

01:00:15.560 very good at those things, by definition, you're not going to be very good at much else,

01:00:19.400 but life is a pretty complicated sport and it requires strength, stability, aerobic fitness,

01:00:26.580 and anaerobic fitness. Yeah. Flexibility. I mean, all of these things. So you have to be able to train

01:00:33.880 all of those things. And unless you're retired, I'm not sure how you'd want to run more than 15 miles a

01:00:40.160 week. If you have to be able to put effort into those other things. So for me, that is the

01:00:44.960 prescriptive takeaway here is how do you have a portfolio approach to exercise? What is your

01:00:53.160 prescriptive approach to patients that I just sort of laid out mine? Well, yeah, you're right on as

01:00:58.340 usual. If you're spending a lot of time, say running, I know a lot of patients who run or cycle like

01:01:05.360 a lot. I mean, 30, 40, 50 miles a week of running and, you know, like an hour or two a day of cycling.

01:01:13.900 It's like you're, yeah, you're getting your, your aerobic fitness really high, but, but it's not great

01:01:20.420 for your skeleton or your, you know, or your balance. Or, I mean, I tell people just after 30 or 45 minutes

01:01:27.060 of aerobic exercise, if you want to do more, you know, circle back home and do some yoga, do some weights,

01:01:32.820 these things that kind of don't necessarily tax your heart the same way that the other high intensity

01:01:39.660 sports do, or, you know, sexual activity, if nothing else is exercise that again, is a totally

01:01:45.520 different realm that is worth investing time and energy into. And, and also, you know, is, is for

01:01:52.580 relationship building. And so, yeah, I think that it's a matter of being more balanced. And also if you,

01:01:58.580 if you try to figure out the area under the curve for, you know, maximizing your heartbeats,

01:02:02.720 you want to do stuff that keeps your resting pulse low, but some high intensity intervals to keep your,

01:02:09.420 your maximal rate, your maximal capabilities high, that'll develop fitness quicker than anything,

01:02:15.020 some high intensity interval training in, in a relatively short period of time. But it's the

01:02:20.800 sort of thing that high volumes of really high intensity exercise is just not, I just don't think it's

01:02:27.600 the ideal approach to fitness. There was a podcast I did with Inigo San Milan, where we talked

01:02:32.660 very specifically and in great detail about zone two, zone two being defined as this area where you

01:02:39.520 have the maximum efficiency of the mitochondria. So you're able to keep lactate systemically below

01:02:47.200 two millimole and just barely keep it there, right? So you're sort of maximum utilization of glucose and

01:02:53.460 fatty acid that is mitochondrial without undergoing non-oxfos. For most people, that's a lower level

01:03:02.520 of activity than they're used to. You know, if you do popular classes, if you hop on a Peloton class

01:03:08.880 or something, you're spending very little amount of time in that zone. You're spending, but you're also

01:03:14.340 spending very little amount of time at peak capacity, sort of north of kind of zone five.

01:03:20.520 You're spending a lot of time in the middle. And I actually think it's that in the middle time that

01:03:25.300 unless you're an athlete who competes in the middle is actually some of the least important

01:03:30.020 areas to be training. A lot of the data looking at even world-class athletes says it's 80% low

01:03:37.500 intensity, 20% high intensity. Of course their total volume is enormous, but I think they even have the

01:03:45.380 ratio right. And yet I think most people don't have that ratio correct. And they don't appreciate

01:03:52.820 how important it is to do that low end aerobic, which depending on your fitness might just be

01:03:57.560 brisk walking. If you're a little fitter, it might be again, zone two level of fitness.

01:04:04.600 One of the things as a cardiologist, people are always asking me, you know, so, so what,

01:04:09.120 what should my heart rate be? You know, what's my training zone and a lot kind of stuff. But for most

01:04:13.680 people, I tell them, you know, I wouldn't pay much attention to your heart rate. I mean, except for

01:04:19.900 the fact that I love activity trackers and, you know, that they can track the pulse and stuff. But

01:04:24.540 I think the most important parameters about pulse are what your resting pulse is. We want to get that

01:04:29.220 nice and low. We want heart rate variability. We want that to be more variable when you take slow,

01:04:34.140 deep breaths, which is why meditation or yoga is a really good thing to add to somebody's

01:04:38.860 fitness regimen. But with respect to trying to, you know, get your heart rate maxed out,

01:04:44.000 it's like, there's a recent study showing in middle aged adults looking at life expectancy as

01:04:50.580 a function of number of steps taken. And people compared to people who are less than 4000 steps

01:04:55.380 a day, people who are getting 8000 steps a day had a 50% reduction in mortality during

01:04:59.900 12 year follow up. And people were getting up to 12,000 steps a day. That was the peak. I mean,

01:05:06.280 it plateaued there. Above that, it didn't go down further. But there was a 67% reduction in mortality.

01:05:12.880 So like you can get pretty much the full benefit of exercise with just a lot of, of steps and most

01:05:19.620 of those being walking, I would agree that you want to add some, some higher intensity interval,

01:05:25.420 but it doesn't take a lot. I mean, like if you look at running, five miles of running a week will

01:05:30.540 give you the longevity boost from running. That's almost as good as it gets.

01:05:36.880 One of the questions patients ask me, and I don't really know the answer. I'm hoping you might

01:05:41.280 is how much resting heart rate is a function of fitness versus genetics. So sometimes because now

01:05:48.060 a lot of our patients do use tracking devices and they often report your lowest resting heart rate

01:05:53.540 overnight, which would really be your true nadir. And I have some patients who say, gosh, you know,

01:05:58.800 mine is 57. Why is it not 47? And I really don't know how much of that is their exercise versus,

01:06:07.600 you know, look, some people just have different size engines that rev at different levels.

01:06:13.140 For example, I've always had a very low heart rate. So nowadays my resting heart rate,

01:06:17.680 my overnight resting heart rate might be in the low forties. But when I was athletic, when I was very

01:06:23.800 fit, I would wake up with a resting heart rate in the mid thirties. So actually I have a pretty high

01:06:28.320 heart rate relative to my baseline now, but I've also never had a very high peak heart rate.

01:06:33.660 So, you know, I've just always thought of myself as having more of a diesel engine.

01:06:37.540 I have to believe that's somewhat genetic. So what is your view around resting heart rate,

01:06:41.920 given that it is a metric people are becoming more and more aware of?

01:06:45.160 So for one thing, females tend to have higher heart rates than males, even at equivalent fitness

01:06:51.160 levels. And that being said, a resting pulse is a much stronger predictor of mortality. Lower is

01:06:58.900 better in that regard. Lower pulse, better longevity in males than in females. Males with a resting heart

01:07:04.600 rate above 85 is not a good place to be. Some of it's genetic. And as people get, you know,

01:07:10.400 into advanced years, some of it's disease, six times syndrome, you know, where your pulse just

01:07:14.960 slows down because, you know, the engine's wearing out and they need a pacemaker. But most of the time

01:07:20.680 it's, you know, it's a function of, well, for instance, like alcohol, the, the, the more alcohol

01:07:25.180 you drink, the higher your pulse will be, your resting pulse, stress, sleep problems. There's a lot of

01:07:31.840 things, but it's generally a pretty good marker of fitness. And so like a lot of things, rather than worrying

01:07:38.200 about how you compare to, you know, your buddy you're working out with is, is how you just compare

01:07:44.000 yourself to you and keep track of your pulse. And you'll notice that when you get into a rhythm,

01:07:50.000 like for instance, one of the reasons I love watching my, my resting heart rate, and I'm kind

01:07:54.860 of like you, it runs, you know, 42, 44 most nights. And if I get over-trained or under-slept,

01:08:01.400 I've been on call, been under more stress, been traveling too much, it'll start raising up to,

01:08:05.900 you know, 47, 48, 49. And, and if you pay close attention to it and use that as feedback,

01:08:11.440 it's a really great way to tune your lifestyle to get into a, like a cardioprotective zone. And it

01:08:17.620 involves the right amount of exercise and the right amount of sleep and not too much alcohol. And,

01:08:22.040 and so, you know, plenty of downtime and play and, and those sorts of things.

01:08:27.620 How much do you see patients resting heart rates improve with appropriate exercise-based

01:08:33.880 intervention? So when you take patients who are underdoing it, which as you said,

01:08:38.080 at the outset, we shouldn't lose sight of the fact most people are underdoing this drug called

01:08:43.400 exercise, but patient shows up with a resting heart rate of 75, who's otherwise quite healthy,

01:08:49.660 has a CAC, their score is places them at the 50th percentile. They're in no grave or acute danger at

01:08:56.000 all. But they say, Dr. O'Keefe, I'm here to get serious about this. I want to, you know,

01:09:00.760 I want to bend the arc of my life. I'm 45 and this is the time to really pay attention,

01:09:05.860 even though there's no heart attack in the next decade of my life at all. And you say,

01:09:10.840 look, I want you to do X, Y, and Z. Is there an expectation that their resting heart rate is going

01:09:15.320 to be 55 one day? 55 only if they get really serious about, you know, say losing 30 pounds and

01:09:23.440 getting fit from unfit. But more typically, you know, five or 10 beats per minute is not uncommon.

01:09:29.000 And you're happy with that. That's a positive sign to you.

01:09:32.520 Oh, absolutely. You know, and of course, it goes along with their waistline coming down and their 0.66

01:09:37.320 blood pressure coming down and their triglycerides lower and their A1C lower. So, you know, these

01:09:42.520 things tend to move in tandem when you kind of dial in your lifestyle and diet and exercise program to

01:09:47.860 that sort of ideal zone. Well, let's pivot then and talk a little bit about nutrition.

01:09:52.720 Gosh, there are so many places to go on this, but something you've written extensively on

01:09:58.900 is the relationship between diabetes and cardiovascular disease and what can be gleaned

01:10:05.720 from that as a model for studying a disease. So tell folks a little bit about that work.

01:10:12.020 Well, this is another thing that I sort of like paid attention to in my diet. And, you know,

01:10:16.740 back when I was in medical school in the 80s and my training in the 80s. And, you know, that was the

01:10:22.900 time when, you know, the Pritikin diet and like a low fat diet was all the rage. And unfortunately,

01:10:28.860 you know, that took a long time to extinguish that. But I started following that

01:10:33.000 pretty closely. And it was a disaster. You know, it's like my triglycerides went from 80 to 300.

01:10:39.640 My HDL went down from 50 to 33. And I just thought, you know, and I was getting skinnier and,

01:10:46.080 you know, my athletic times weren't better. And in fact, they were worse and I wasn't feeling that

01:10:50.200 good. I thought this is not the right diet. How restricted were you?

01:10:55.360 Well, like, for instance, when I, you know, I was a 20 something, you know, so I'd go out to eat with

01:10:59.700 friends and we'd be eating pizza or, and I'd take off the toppings and just eat the crust, you know,

01:11:05.100 and then, and then for a while, then I kind of got into the sort of keto phase and I would eat the

01:11:09.300 toppings and throw away the crust. And then I figured, yeah, pizza, probably just not worth

01:11:13.920 eating at all. So, you know, and I'd eat lots and lots of white rice and, you know, and try to

01:11:19.680 minimize fat. And, and then I realized, you know, you can't generalize. For one thing, that's a

01:11:25.060 disaster for, and it's played out on a, on a population wide level in America, that kind of

01:11:30.760 diet, you know, makes us fat, belly fat, triglycerides are up, diabetes rates are up, it makes you hungry all

01:11:37.220 the time. It is not the right diet. Just two days ago, we published a, an article in our,

01:11:43.800 our flagship cardiology journal in the world called the Journal of American Culture Cardiology

01:11:48.080 called the PESCO Mediterranean Diet of Intermittent Fasting as like the omnivore solution to the

01:11:55.480 omnivore's dilemma of what to eat. And we think if you put together like all the data and the

01:12:00.460 guidelines and, you know, the observational data and a little bit of randomized data that we have that

01:12:05.840 a diet that's moderately high in fat, very low in refined carbohydrates, like almost no added sugar

01:12:11.800 and minimal white refined grains, but, but high in nuts and extra virgin olive oil and high in fish

01:12:18.500 and seafood and high in vegetables and low in processed food and drinking mostly water, tea, coffee,

01:12:25.880 fasting for at least 12 hours, each 24 hour period of time, and preferably moving more like to a,

01:12:30.960 like a 14 or 16 hour fast per day. We think this is like arguably the healthiest cardiovascular diet,

01:12:38.920 both for preventing diabetes, but also preventing heart disease and dementia, obesity, and a lot of

01:12:45.040 the other scourges that are so common in our society. The PREDIMED study, which I'm sure I've

01:12:51.360 discussed in great detail on a previous podcast, though, unfortunately I can't recall, hopefully in the

01:12:56.300 show notes. If it's been done, we'll make sure to link to it. Probably one of the most impressive

01:13:01.440 diet studies with respect to cardiovascular disease prevention. And, you know, I think the

01:13:05.460 findings of that, though they needed a revision based on an error and randomization the first time

01:13:10.800 around were, were difficult to ignore when you consider the challenges of studying primary

01:13:16.020 prevention, even with drugs, let alone with a diet. And yet to see the success of a Mediterranean diet

01:13:22.820 in that study, that was a wake-up call for me. Peter, that is, in my opinion, the most important

01:13:28.500 diet study that's, that's been done. Emilio Ross was the primary investigator on that. He, he was a

01:13:34.560 co-author on this recent paper that we wrote, and Emilio and I have been working together on a lot of

01:13:40.060 projects recently, but, but it was the Mediterranean diet versus the American Heart Association diet, which

01:13:45.080 is that diet that we were just, you know, dissing that's, you know, the low-fat sort of trending towards

01:13:50.680 vegetarian diet that's high in carbs. But, but that showed in this group of 7,500 people followed for

01:13:58.120 four and a half years that the primary endpoint, which was MI, heart attack, stroke, or cardiovascular

01:14:04.200 death was reduced to 30%. But also follow-up studies showed that the dementia, cognitive impairment,

01:14:11.180 diabetes, obesity were also, each of those were significantly reduced in the people that got the

01:14:16.660 Mediterranean diet. But it's important to point out that they were specific Mediterranean diets that half

01:14:22.140 of the people in the Mediterranean diet got a free liter of extra virgin olive oil per week that they were

01:14:27.040 supposed to use up in a week. And the other half got mixed nuts, tree nuts that were almonds, walnuts, and

01:14:33.860 filberts or hazelnuts. So they were adding fat in the case of the nuts, you know, vegetable protein. And when you,

01:14:41.100 when you do the multivariable analysis on what correlated best, it was the added fat. It didn't increase

01:14:45.520 saturated fat, but it increased these healthy fats from these healthy foods. And, and as Emilio likes

01:14:51.600 to point out with the olive oil, you know, it has to be not only extra virgin, but more importantly,

01:14:55.540 it needs to be highly high in polyphenols, which is perceptible as this black pepper stinging at the

01:15:02.360 back of your palate, you need to every time you open a bottle of olive oil, because it's not on the label,

01:15:06.520 generally, the polyphenol content, you taste it, and it should have this, this, this burn 10 or 20 seconds

01:15:12.320 after you swallow it in the back of your palate. Those are super important antioxidants that because

01:15:18.960 they're dissolved in oil, they seep into your blood vessels, they seep into your brain and your eyes and

01:15:26.180 your skin. And they really correlate with good long term health, whereas there's been studies,

01:15:31.400 decades, Dr. Vogel and his colleagues did a study showing that olive oil was bad for your endothelium.

01:15:35.800 And that never made sense to me. And then I realized, oh, they were using a, like an, you know,

01:15:40.160 antioxidant depleted, not, not one of these high polyphenol antioxidant olive oils. So it's really

01:15:45.360 important to look for those high antioxidant olive oils and then use them generously.

01:15:50.160 So, so two comments. One is most people, if they go to the grocery store, myself included,

01:15:55.060 historically, aren't really paying close attention to what olive oil is. And boy, you only need to get

01:16:01.220 fooled once, which is to say, catch what the label says to really get upset. But a lot of things that

01:16:06.120 are marketed as, you know, pure extra virgin olive oil or anything, but, and I don't know how they

01:16:10.820 get away with it. Truthfully, it's, it's, it's really an embarrassment to how this stuff is regulated,

01:16:14.700 but it's basically a bunch of canola oil that has some olive oil in it. And they, they, they've

01:16:18.960 somehow managed to lie their way into saying it's pure olive oil. So you have to be careful what you

01:16:23.080 buy. But because of those, because of that, that's the prediment study though, had the

01:16:28.420 intervention of extra virgin olive oil or nuts. And we have a rare thing, by the way, as you're

01:16:33.620 always pointing out, we have first level randomized data showing that adding this to the diet will

01:16:39.380 reduce heart attack, stroke and cardiovascular death. And, and so, I mean, it's also, you know,

01:16:43.520 these are delicious foods when you get used to eating them. And, and, you know, if you want to

01:16:46.960 follow a high fat sort of ketogenic diet, it should be high unsaturated fat. It shouldn't be cream and

01:16:53.100 cheese and butter and red meat. It should be, it should be nuts and seeds, extra virgin olive oil,

01:16:59.980 avocados, and oily fish, like salmon. It's only those five things. I mean, you need to get a lot

01:17:05.300 of your calories from those five things, which by the way, is kind of the traditional peasant 0.97

01:17:10.500 Mediterranean diet. These weren't, these weren't Mediterraneans that are living high on the hog. 0.93

01:17:14.160 These are the peasants who were growing their own vegetables and tending their own olive garden and

01:17:19.180 their own grapes and the red wine and that sort of thing. So. So how convincing do you think are

01:17:25.100 the data demonizing saturated fat, given that so much of it is in the context of refined carbohydrates

01:17:33.140 and other things? I mean, again, when you look at the epidemiologic data, unfortunately, we just don't

01:17:38.220 have big enough cohorts of people who consume saturated fat absent carbohydrates or refined

01:17:44.860 carbohydrates. It saturated fat in epidemiology becomes a proxy for people who are probably

01:17:50.060 eating a lot of other bad things. So mechanistically maybe, or, or otherwise, what are you, how do you

01:17:56.200 feel about it? I'm actually like what people ask me about, you know, what's the most important thing

01:18:00.880 of the diet? I don't mention getting rid of red meat or getting rid of saturated fat. I mean,

01:18:05.380 a moderate amount of that is, you know, again, our evolutionary history, you know, we, we ate a lot of red

01:18:12.080 meat and we ate saturated fat. The evil white crystal in the American diet is not salt. The worst

01:18:19.440 is sugar. And sugar and refined carbohydrates are by far the absolute worst dietary villain.

01:18:26.540 Saturated fat, you know, a little bit of butter is not going to kill you, you know, like, like if

01:18:31.280 you're a vegan, there's nothing you can eat that'll be healthier for you than like a juicy steak. It's not,

01:18:38.320 it's not overdone, you know, because, because you're probably low in, in the things like B12 and

01:18:44.720 zinc and iron and high quality protein. So yeah, it's, it's a natural food. And in moderation,

01:18:50.380 I mean, I think saturated fat, excessive saturated fats, not a good idea, but we don't focus excessively

01:18:56.960 on it. My wife, Joan is a, is a really smart dietitian. And like you, you know, we went to school 0.64

01:19:02.820 till we were 32 or 33 to promote health and wellness and we got zero, nothing. I mean,

01:19:08.760 hardly an hour of training in nutrition. It's just so embarrassing that it's still like that. But,

01:19:13.860 but so, you know, she kind of taught me a lot of the fundamentals and still continues to teach me a

01:19:19.040 lot of fundamentals of nutrition, because this is an important thing. And, and any good dietitian will

01:19:25.040 tell you that, you know, red meat and saturated fat are essential nutrients that they're not toxic in

01:19:30.940 and of themselves. So you touched briefly on salt. I know you've written about not just salt,

01:19:36.520 but also magnesium. And that's something that's also really near and dear to my heart.

01:19:40.860 Our patients consume a lot of magnesium, both in the form of oxide, which we basically titrate as

01:19:47.140 high as they can tolerate from a bowel function perspective. And then we use, you know, slow mag

01:19:51.660 typically just to make sure that nobody's getting any sort of cramping or anything like that. But

01:19:56.300 my thesis is there's a global shortage of magnesium in the human, somehow we're just not getting enough

01:20:03.100 magnesium now. I, I don't know why that's the case, but my proof for that, if that's too strong

01:20:08.460 a word is that when you give people back on the order of two grams of magnesium a day, they always

01:20:16.040 feel better. Why is that? Well, it's the same story with potassium, Peter, by the way, our evolutionary

01:20:24.640 ancestors living out there in the wild, eating wild game, nuts, all the vegetables and fruits we're

01:20:31.820 getting like, and fiber is the same way, you know, like five times more, they were getting a lot more

01:20:38.100 magnesium, a lot more potassium, a lot more fiber than we're getting today. So when you add those

01:20:43.960 things back to the diet and the best way to do it is with lots of, I mean, nuts are high in magnesium,

01:20:48.360 but I agree the other thing. So basically I think it's like getting us back into sort of like an

01:20:54.140 ideal range of consumption of a really important mineral. I mean, it's, it's an important cofactor

01:21:00.480 for a lot of the most essential, you know, sort of chemical reactions going on in our body, magnesium is

01:21:05.520 so it's, it's really important, but it's also makes me think that, you know, a concept that I've

01:21:12.280 come to recently that I think, I think you'll, you'll like, and you probably think this way as

01:21:17.580 well. But again, if you look at our ancestors, when they would get a bird or a mammal or a fish

01:21:24.440 or a squirrel or whatever, and they would cook it or a buffalo for that matter, and they'd cook it,

01:21:29.800 they would eat nose to tail, right? They'd eat the whole thing. These days when we eat meat, we usually

01:21:35.520 eat muscle meat, which is a very narrow sort of range of animal-based nutrients. One of the things

01:21:42.640 when you eat nose to tail, say when you're cooking the bones, for example, you cook them long enough

01:21:48.120 to eat them, you get a bunch, and the skin for that matter too, a bunch of collagen. You get calcium

01:21:54.680 hydroxyapatite, which is a form of calcium that we're meant to eat. We weren't meant to eat rocks,

01:21:59.900 which is the standard calcium supplement. It's calcium carbonate, calcium gluconate. Those are rocks.

01:22:04.240 We didn't eat rocks. We ate bones. And for the last 5,000 years, we ate dairy. But a lot of people

01:22:10.820 have trouble, you know, tolerating the lactose. And so we think that, and the Mediterranean diet

01:22:15.460 really focuses on fermented dairy. But getting back to, like, I think the other supplements that

01:22:20.560 are really important is like an organic bone meal that's high, that you have to add magnesium to it,

01:22:25.280 because that's calcium hydroxyapatite. And if you get that up to, you know, the gram a day

01:22:29.880 of calcium from there, and then your magnesium, I would agree, two grams per day. And then the

01:22:35.440 collagen, because you're not going to eat enough skin to get the collagen that we're meant to get,

01:22:40.240 the collagen supplement, like whether it's pills or powder, is really, really good for hair, skin,

01:22:46.600 and nails, not to mention bones. And it's also good for putting on healthy muscle and maintaining

01:22:51.080 healthy muscle. I mean, this is like ideal protein, glycine and other amino acids that, by the way,

01:22:56.580 we're really meant to have in our diet. So I think those are really important supplements to that

01:23:02.140 sort of healthy Mediterranean, pesco-Mediterranean diet. But the fasting, I think that it's good to

01:23:07.260 add, because it's hard to get those kinds of minerals at those levels. Do you restrict sodium

01:23:13.760 in any subset of your patients, including maybe even those that are both hypertensive with compromised

01:23:20.420 kidney function? We see a lot of really sick people with, you know, with class four heart failure,

01:23:26.220 bad kidney disease and whatnot. And there you have to do be somewhat careful. But I virtually never

01:23:31.720 tell people to do that less than 1500 milligrams of sodium. And you're better off having sodium kind

01:23:37.360 of in the medium range, you know, from two to three grams per day. And actually, a good rule of thumb for

01:23:43.740 like the listeners here, and generally healthy people is like, eat mostly whole natural foods,

01:23:50.060 which are very depleted, you know, sodium poor, right? And then salt to taste. Because a lot of

01:23:56.180 the healthiest foods you'll eat, like vegetables, nuts, fish, you'll eat a lot more if you can salt

01:24:01.820 it to taste and make it taste good. And when you add salt to those natural, you know, or lightly salted

01:24:07.140 nuts, I mean, you don't need to worry about that. That's good for you having some salt in your diet

01:24:11.060 when you're eating an otherwise naturally healthy whole foods diet.

01:24:14.440 All right, let's go back and talk about that drug that I'm so enamored with, or class of drug,

01:24:20.520 there are at least two out there. Tell folks what an SGLT2 inhibitor is, besides a mouthful.

01:24:28.420 Yeah, an SGLT2 inhibitor, you know, is a diabetic drug that blocks this sodium glucose co-transporter

01:24:35.240 in the tubule, in the nephron. When we filter our blood through the nephron, through the kidneys,

01:24:41.160 we pull out a lot of things, you know, water, sodium, toxins, urea, including glucose. And then

01:24:48.860 because the body is saying, there's no reason to waste this glucose, you know, we need these calories.

01:24:53.640 So it reabsorbs the filtered glucose before the urine goes out. So we figured, they engineered a

01:25:00.500 drug to block the reabsorption of that glucose that's filtered. And when this drug, when these

01:25:05.960 class of drugs first came out seven or eight years ago, I'll have to tell you, Peter, I thought, 0.97

01:25:09.060 this is a dumb idea. I mean, everybody knows that glycosuria is terrible for the kidneys. And this

01:25:15.200 is like, it may be lower sugar, but in the long run, it's going to be, but that's the beauty of

01:25:20.460 science. That's why you do these big randomized placebo controlled trials. And when the first one

01:25:24.580 came out, the EMPAREG study about five years ago, like my phone and text and emails just lit up with

01:25:31.380 people from around the country, around the world, friends who were saying, did you see this? This can't

01:25:34.840 be true. Keeping in mind, we've been trying to prove for 40, 50 years, 100 years since the first

01:25:40.820 diabetes drug, insulin came out, that controlling sugar prevented cardiovascular death. And we

01:25:46.180 couldn't prove it, shockingly, until this trial came out and it, you know, reduced cardiovascular death

01:25:50.980 38%. It reduced heart failure, renal failure. I mean, it was just an amazing thing. And subsequently,

01:25:59.160 there's been, oh, a good seven mega trials now, you know, between three and 17,000 patients in each

01:26:08.580 study randomized to SGLT2 inhibitor or placebo that shows that in fact, these are the most potent

01:26:15.980 drugs for, I mean, not for lowering sugar, they do that modestly, but for, for improving cardiovascular

01:26:21.540 prognosis, reducing heart failure, and renal failure. And it's just fascinating to, you know,

01:26:26.780 speculate about, about the mechanisms of action, but may have something to do with ketones. But the

01:26:31.540 most shocking thing about this, that's really blown the lid off is, is that these drugs reduce things

01:26:37.780 like heart failure, deaths, heart failure occurrence, and renal failure in people without diabetes, as well

01:26:45.760 as with diabetes. So that really makes us wonder. Well, that's why I take one. And they're currently

01:26:53.980 being studied, frankly, as just straight up longevity agents, for exactly that reason. And I'm

01:26:59.680 actually, my interest in this even goes a bit beyond that of metformin, which has historically garnered

01:27:06.100 much of the longevity attention in the diabetes medication repurposed camp, because I like the

01:27:13.760 mechanism of action more. I like what it doesn't do. Again, I think metformin is an amazing drug. I think

01:27:18.920 it's, it's efficacy in people with diabetes is remarkable. I do have my concerns about its

01:27:24.400 efficacy in very healthy people who exercise at the upper limit of what we've discussed. And I think

01:27:31.020 it might, it might impair there. I think it's too soon to say I've had lots of interesting discussions

01:27:36.120 with people and we're actually in the process of designing a study now to test that. But to me,

01:27:41.140 this is a drug that doesn't really show any evidence of impairing the benefits of exercise

01:27:47.040 and yet offers through totally different mechanisms, some of those cardioprotective benefits. So

01:27:51.960 the good news, as you pointed out about science, is it just over time, it keeps accumulating

01:27:57.660 information and we'll get better and better answers.

01:28:00.000 Churning away. And, you know, but so it's so fascinating to think about how this works. And

01:28:04.000 I don't prescribe metformin for people without diabetes. I mean, it upsets your stomach. It kind of

01:28:09.880 makes you feel a little queasy. I use it on all my type two diabetics, but I always

01:28:15.800 understand that the SGLT2 inhibitor is more important. It burns off belly fat. When you,

01:28:21.780 even a non-diabetic person takes, takes an SGLT2 inhibitor, you urinate out about 100 grams of sugar

01:28:28.580 a day. So we were talking about the evil crystal compound, you know, white, the sugar. This basically

01:28:35.320 is like pulling the plug and draining a substantial amount of sugar from your body every day. It's like

01:28:40.320 following a ketogenic diet without having to follow that. I mean, it raises ketones in the

01:28:46.040 low, in your system because of the fact, and it does tap into belly fat. It taps into belly fat to 0.64

01:28:52.260 get the fatty acids that then turns in, the liver turns into ketones. So, and we're still don't fully

01:28:57.880 understand how it works, but it's an important drug class that is going to only get bigger with

01:29:02.820 respect to its impact on health and longevity. Why do you think it hasn't shown an increase in

01:29:08.740 UTIs or bladder cancers or things like that? I mean, cause I, so seven years ago, that was my

01:29:14.080 thinking, right? Which was, oh, interesting idea, but you're going to have a UTI every week. No,

01:29:20.520 thanks. Like, I don't, I don't see how that's a good trade-off and it just hasn't panned out.

01:29:24.560 Why do you think that is? It's sort of interesting because, well, when you think about it,

01:29:28.960 the UTIs, you're getting rid of some glucose in the urine. It actually, the only predictable side

01:29:35.600 effect that you see, and it goes up, especially in females, is topical yeast infections, you know, 1.00

01:29:42.200 fungal infections down in the groin regions on the genitalia. And, you know, when you think about it,

01:29:46.180 you are putting sugar in water in warm, moist places. So I tell people on an SGLT2 inhibitor,

01:29:53.780 they need to, you know, pay special attention to use a wet wipe after urination, especially females, 1.00

01:29:58.140 because there's, you know, just more surface area there to get a yeast infection on. But,

01:30:02.360 but it is sort of interesting that it doesn't really increase things like UTI or pyelonephritis

01:30:07.800 or urosepsis. So it may be just that it's making the system otherwise healthier. You know, your immune

01:30:14.260 system, your, your kidney function, your codivastro system, maybe it's just, you know,

01:30:20.260 you're better able to deal with that. I don't know.

01:30:22.300 So this really brings it back to this point, which is, you said something earlier that I think is

01:30:28.340 worth coming back to. When you take a patient with type two diabetes, you take two patients with type

01:30:36.600 two diabetes and you give one of them a lot of insulin and you give the other one, not as much

01:30:46.380 insulin. One of them is going to have lower blood sugar than the other. In the one with lower blood

01:30:54.220 sugar, we see less microvascular disease. We see that they have fewer amputations, less kidney disease,

01:31:06.080 lower rates of impotence. Basically any tiny, tiny blood vessel in their body does better when

01:31:11.480 their glucose goes down. But if it came down on the heels of insulin going up, we don't see a

01:31:20.580 reduction in cardiovascular disease. So why is it in your opinion that lowering glucose with more

01:31:28.220 insulin does not reduce cardiovascular mortality, which is so clearly tied to type two diabetes and

01:31:36.940 postprandial glucose? This is the key issue. Okay. And you know, the answer to this is that insulin is the

01:31:46.320 problem. Insulin is a really super important hormone that Jason Fung and you guys, and you had a really

01:31:53.820 wonderful discussion about this, but insulin sort of ushers nutrients, fats, and glucose into cells to be

01:32:00.820 burned. Or if you're not burning, you're not in a burning mode right now, you're not exercising, you're

01:32:04.980 sitting around, you're sleeping. It stores them as belly fat. So insulin is super important if you have

01:32:11.240 type one diabetes. And type two diabetes, I consider it the court of last resort. I mean, this is an

01:32:16.160 obesity hormone. Insulin and cortisol are the two obesity hormones. You want to get somebody fat,

01:32:20.880 put them on insulin, put them on prednisone. They will get belly fat like crazy. And I always felt

01:32:26.480 sorry for these diabetics. You know, the endos would be putting them on all this insulin. I'd be telling 0.76

01:32:31.100 you got to get your weight down. That's impossible. You cannot get your weight down when you're getting

01:32:35.980 a lot of exogenous insulin. You're hungry all the time. It causes weight gain. It causes fluid

01:32:41.180 retention. If anything, it accelerates atherosclerosis, you know, high insulin levels. The key

01:32:46.600 is low. You want to, you want to drive your insulin levels as low as like your pulse. You want a nice

01:32:52.560 low insulin levels. They go up when you eat and then they go right back down. And the way you do that is

01:32:58.300 you exercise, you minimize belly fat, you eat a diet like we were just talking about.

01:33:03.640 You get no sugar. None of that easily digestible refined carbohydrates. You eat a lot of fiber,

01:33:09.780 a lot of low glycemic fruit, but more, more, more sort of non-starchy vegetables. Eat modest amounts

01:33:16.060 of lean protein and a little bit of saturated fat don't hurt you. You eat a lot, like 50% of your

01:33:21.400 calories from unsaturated fats from those, you know, nuts and olive oil and avocados, guacamole and

01:33:26.460 salmon and sardines and trout. And you will have, you know this from wearing a glucose monitor. I've

01:33:32.020 worn a glucose monitor for a while too, being non-diabetic. I found it a really great behavior

01:33:36.680 modification thing. But when you eat that way, you don't see your glucose go up at all. So when

01:33:41.280 your glucose goes up, your insulin doesn't go up. And when your insulin stays low, your vessels are

01:33:45.820 happy. You're not putting on belly fat. We wrote an article called, you know, insulin is a

01:33:50.840 cardiotoxic medication. I mean, we, we want to minimize the amount of insulin. Unfortunately,

01:33:55.780 it's new, these new drug class, SGLT2 inhibitors, GLP-1 agonists, that's semaglutide and dulaglutide.

01:34:03.120 There's a couple others. These two together, along with metformin for diabetics, amazing growth.

01:34:08.720 They all lower insulin. They all reduce fat, belly fat, and they all improve cardiovascular prognosis.

01:34:15.720 And by the way, you know, a lot of it has to do with the effect on insulin.

01:34:19.200 Tell folks how the GLP-1 agonists work. We didn't, we might as well round out that trifecta.

01:34:25.340 Yeah. So GLP-1 agonists work by supplying a hormone that tends to wane in people as they develop

01:34:33.200 type 2 diabetes. This is a hormone that tells after you eat, it tells the pancreas to give a

01:34:39.160 shot of insulin. And when you're not eating, it also tells, it shuts down glucagon production in

01:34:44.320 the liver. So you're making less glucose, gluconeogenesis when you don't need to be. And that's

01:34:49.160 one of the problems when you're eating this junky diet, you get these incretin levels get

01:34:53.240 low, you get this gluconeogenesis. So you wake up in the morning, even after not eating for

01:34:57.920 eight or 10 hours and your glucose is high because you're making glucose when you don't

01:35:01.580 need to be. So this basically restores a hormone that is, that is low and it sort of balances

01:35:07.880 out, kind of lowers fasting insulin and raises postprandial insulin. And incretins also slow

01:35:15.040 bowel motility. So that slows absorption. So you don't get the big spikes in glucose and actually,

01:35:21.760 you know, kind of makes you feel full faster. So these are wonderful drugs for weight loss. I'm

01:35:26.520 using in some of my patients now, high dose semaglutide and it'll, it'll lose up to 10%

01:35:31.480 body weight in a very safe way. I mean, even in non-diabetics, very safe way to get your weight

01:35:36.680 down. And I'll combine it with SGLT2 inhibitors in non-diabetics. It works, reduces cardiovascular risk.

01:35:42.580 So people, people on GLP-1 agonists tend to complain of some, when you first start it and

01:35:47.880 when you does titrate it every week, some constipation and or nausea, but those go away

01:35:53.880 with time. And it is FDA approved for weight loss, isn't it? At least one of them is, right?

01:35:58.480 It is. One of them, liraglutide is sextenda, but it's a once a day drug. This, you know,

01:36:05.780 the semaglutide will be approved in the next year as a once a week drug, the way we use it for

01:36:10.940 diabetes and at a higher dose, 2.4 milligrams rather than one milligram for the top dose. And,

01:36:16.720 you know, it's shown it's just best ever weight reduction. And, uh, you know, it's sort of an

01:36:21.720 alternative to, uh, to bariatric surgery for these, you know, really overweight patients.

01:36:26.420 And wow, I didn't realize that. So you're telling me that you can now take a GLP-1 agonist once a week

01:36:33.460 with a sub-Q injection and achieve comparable levels to the normal daily injected routine.

01:36:39.680 Cause that's historically been one of the barriers.

01:36:42.660 Better, better cardiovascular reduction. It reduces heart attacks, stroke, cardiovascular death

01:36:46.820 better than the daily one, the liraglutide. These are also revolutionary drugs, but the cool thing,

01:36:53.880 they're very safe otherwise, you know, and whereas the SGLT2 inhibitors, you kind of reduce heart

01:37:00.480 failure and renal failure and overall cardiovascular mortality and all cause mortality in sicker people.

01:37:07.120 This reduces more of the atherosclerotic cardiovascular disease. It's, it has a

01:37:11.700 stronger effect on MI stroke and, you know, those ruptured plaques we were talking about at the

01:37:15.620 beginning. They cause weight reduction from two different mechanisms of action. They improve

01:37:20.380 cardiovascular prognosis from two different mechanisms of action, and they really work well

01:37:24.460 together. It's a phenomenal combination. Well, we can't have a discussion about medications

01:37:29.020 in cardiovascular disease without talking about statins, which you've written about a lot,

01:37:33.280 certainly would have to be in the top three most prescribed classes of medications out there.

01:37:38.740 You know, I'm kind of a five statin guy. There's a lot out there, but there's probably only five

01:37:43.020 that I'm, that I'll use in patients. And I, every physician I think who prescribes these has their

01:37:48.740 own little secret alchemy around it. You know, when they're using Livolo versus Prevastatin versus

01:37:53.800 Crestor versus Lipitor, et cetera, but let's talk broadly about them as a class. So obviously a type

01:38:00.800 of drug that inhibits the synthesis of cholesterol, which is its direct action, but the money may come

01:38:07.060 more from its indirect action, which increases the LDL receptor on the, on the liver. And you're

01:38:13.740 pulling that ApoB bearing particle out of circulation, and you're having this pretty pronounced effect

01:38:19.440 in terms of LDL-C and ApoB reduction, second really now only to PCSK9 inhibitors.

01:38:27.860 But rather than talk about that, although I'm happy to hear your thoughts on that, I want to talk a

01:38:32.380 little bit more about the potential other benefits of statins, because I think this is where most people

01:38:38.620 do believe there are pleiotrophic benefits of statins, but they're, they're harder to quantify.

01:38:43.360 And I'm sort of curious as to what your thinking is on when you want to bring a statin in. Is it also

01:38:51.040 something you use in patients whose ApoB might not be that high, but for whom you're looking for this

01:38:56.280 other benefit? The latest pleiotrophic effect, if you will, on statins is there was a study just this,

01:39:02.720 this week came out that people who are on statins seem to have some better sort of resistance to

01:39:09.520 severe COVID infection. And it may be that, you know, the people that get a lot of inflammation

01:39:15.460 are the ones who are more likely to have a bad outcome with the COVID infection. But in any event,

01:39:20.700 they do have anti-inflammatory effects. And we use them a lot. And I'm always arguing with my patients

01:39:26.300 about statins. And, you know, they'll say, have you read about these things on the internet? These

01:39:31.540 are like, and I'll point out to them, in the history of science, in the history of medicine and

01:39:37.340 randomized trials. There's never been a class of medications that have been so thoroughly tested

01:39:41.300 in gold standard, randomized placebo-controlled trials, lasting up to years. There's like 500,000,

01:39:47.380 half a million people in various randomized trials showing that if you have heart disease,

01:39:52.920 or especially if you've had a cardiovascular event, they will help improve your prognosis.

01:39:56.840 They reduce MI, stroke, cardiovascular death, probably all cause mortality of high-risk people.

01:40:01.320 Pause for one second, James. I agree with you completely. There is no drug, no class of drug

01:40:08.900 I spend more time defending than statins. Why is that? Why is it that the internet is absolutely

01:40:17.120 crazy with this obsession that the statin is a drug planted here by foreign operatives designed

01:40:27.080 specifically to kill us? Yeah, it's crazy. It's a combination of things. Number one,

01:40:34.860 and I was kind of skeptical about this, but then I started taking a statin back about, you know,

01:40:38.920 when I was 45 and I had that calcium score. And when you, when I was working out hard, like I wouldn't

01:40:44.640 read my, like my muscles would hurt harder, you know? I mean, like they would ache, they would ache

01:40:48.940 worse after a hard workout. And, and then, so I started taking Coensin-Q10 and switched over to a,

01:40:54.720 you know, a more of a less potent one and sure enough, they got better. So they frequently are

01:41:00.380 associated with these nuisance side effects, like, like muscle aches. And some people swear that

01:41:05.880 causes some brain fog, some sort of mild cognitive impairment. But a lot of it too is, you know,

01:41:11.380 is sort of the nocebo effect, the voodoo effect. You know, they read about this in the, you know,

01:41:16.620 and there's all sorts of people, you know, trying to capitalize on selling people alternatives to

01:41:21.940 statins. That being said, I argue with people about statins who really need them. The 55-year-old

01:41:29.000 just had an MI who tells me, you know, I'll do anything but take a statin. Fortunately, now we do

01:41:33.580 have other good options. Zetamide lowers cholesterol by reducing absorption by blocking the Neiman-Pick

01:41:40.100 receptor and PCSK9 inhibitors, which just prolong the life of LDL receptors, both really elegant ways to

01:41:46.960 lower cholesterol by removing it from the circulation without poisoning the cell's ability to make

01:41:51.460 cholesterol. So that's really, really important. And I know you were talking to Dr. Dayspring about

01:41:56.500 that. And I completely agree. So we have an option for those people who are statin intolerant.

01:42:01.900 Because ezetamide and PCSK9 inhibitor, they work synergistically like statins and PCSK9 inhibitors

01:42:06.800 or ezetamide with statins. But for people who have a zero calcium score, who are at relatively low risk,

01:42:14.580 we do the MESA risk calculator or the ASCVD 10-year risk, and they're under seven, lots of times they're

01:42:19.360 one or two or three. Like it's hard to improve somebody who's got such a low risk. And then I

01:42:25.520 say, you know, let's not get overly shook up about your LDL. And let's just, you don't need your statin,

01:42:31.440 we can stop your statin, we don't need to start it, whatever. And we'll focus on diet and exercise and

01:42:35.260 lifestyle. But in middle-aged people, I need to see that, that zero calcium score or low calcium score to do

01:42:41.980 that. But yeah, statins are a wonderful tool. They're cheap. And we use a lot of them, but we

01:42:47.520 also stop a lot of them. And I think for, I'd be fascinated to hear this. I've thought about

01:42:53.040 writing a paper on this topic, because there's nothing out there in literature, but you kind of

01:42:57.040 touched on it on one of your sessions, I think it was with Tom Dayspring, that to the extent that

01:43:03.800 statins do sort of impair a cell's ability to make cholesterol, it does that not only in the liver

01:43:10.660 that makes the most of cholesterol, but it does not in the brain. And people say, it doesn't matter

01:43:13.940 about getting cholesterol too low, because cells can, if your brain makes its own cholesterol,

01:43:18.400 if it does, if it needs it, if it's not poisoned, the HMG isn't poisoned by the statin. But if it is,

01:43:24.940 that gets into the brain, and it can't make its own cholesterol. And when you look at demented people,

01:43:30.220 they have lipid depleted brains, you know, this shrunken brain. I mean, there's a good study showing

01:43:35.040 that omega-3 helps to keep your brain plump, a high omega-3 diet. And for that same reason,

01:43:39.860 I have some sense that we might be better off using non-statin approaches to lowering cholesterol,

01:43:47.980 like PCSK9 inhibitors, omega-3, azetamide, a good diet, and other people that if we want to

01:43:55.320 maximize sort of cognition and reduce Alzheimer's disease down the road.

01:44:00.000 Tom, of course, works very closely with us in our practice. And that's absolutely been our approach,

01:44:06.040 which, of course, puts us at odds with many of the people that are in the very strong pro-heart camp,

01:44:13.260 very organ-specific camp. We look at two markers of cholesterol synthesis, desmostrol and lithosterol.

01:44:19.820 We monitor them very closely. And there is a small body of literature that says, at least in high-risk

01:44:25.960 people, maybe people who carry one or two copies of an APOE4 gene, that very low levels of desmostrol

01:44:34.420 and or lithosterol in the presence of statins may be a predictor of increased risk. And we just,

01:44:42.280 in that situation, based on all the reasons you've laid out, play to the precautionary principle.

01:44:47.980 And frankly, you know, our application of that is there's probably only two patients in my entire

01:44:53.000 practice that are going to walk around with a desmostrol below 0.5, because there are so many

01:44:58.640 other options if we need them that we don't need to overly suppress cholesterol synthesis.

01:45:03.400 So only in the most high-risk cases of cardiovascular disease, when we have no

01:45:08.380 real other options, then we do this. But otherwise, you're right. I mean,

01:45:13.040 we're incredibly liberal with the use of Zetia. And I think physicians are becoming more liberal with

01:45:18.940 that, which I think is great. Coupled with, frankly, Prevastatin is my favorite statin,

01:45:24.380 if I can get the results there. You know, it's so mild. Also, anecdotally, seems to produce less

01:45:30.720 symptoms. It also raises, it doesn't raise glucose the way, say, atorvastatin or prevastatin will.

01:45:36.480 And it doesn't increase risk of type 2 diabetes. And when you use it with azetamide, which, again,

01:45:41.820 we have a great study, the Utopia study, in primary prevention, azetamide reduced cardiovascular

01:45:47.700 events by 30%. And then we also have the improvement study that showed that if you combine it with a

01:45:52.980 statin, it would reduce cardiovascular events. So we have really good first-level evidence about

01:45:57.040 azetamide. The only thing I would disagree with you on, and disagreement might be too strong a word,

01:46:02.520 is tell you how I think about things a little bit differently, is I don't look at a 10-year risk

01:46:07.760 calculator. That's one area where in my practice, we just have to do things a bit different, which

01:46:13.180 means we have to deviate from guidelines. Because I agree with you. Look, if a person's 10-year risk

01:46:19.240 is 2% and their calcium score is zero, but their APOB is at the 80th percentile, the textbook answer

01:46:27.020 is do nothing. Once you've exhausted all the lifestyle modifications. My view on that is,

01:46:33.140 if you're 40 years old and your 10-year risk is zero, congratulations, but I'm playing a different

01:46:38.760 game, right? I'm really in this camp of Alan Snyderman that says we have to be taking a 30 and 40-year

01:46:45.700 view of cardiovascular mortality. And that means I can't look at a 10-year risk calculator. I have

01:46:51.780 to take a longer arc. And sometimes that means primary prevention is adding drug to treatment

01:46:59.300 of all other variables, even if the calcium score is zero. But again, that's a patient's decision based

01:47:05.820 on their appetite for risk and their appetite for longevity. So I completely agree. And at least I

01:47:13.120 don't know of 30-year risk calculator. So that calculator you're using is in your head. And, you

01:47:18.560 know, I'm sure that's a very good calculator. But one point I would make is that in those kind of

01:47:24.240 people, and I would say myself included, I don't take a statin. I haven't for years. I don't have a

01:47:30.400 lot of risk factors, but I did have a little bit of calcium when I checked it years ago. So I'm sure I

01:47:34.580 have more now. Statins will accelerate coronary calcification, by the way. So I use azetamide

01:47:40.140 with a PCSK9 in my cell because it doesn't have any side effects. Neither of those have

01:47:45.200 side effects. I mean, rarely, rarely. And they work through very elegant mechanisms that don't distort

01:47:50.360 your sort of milieu of cholesterol homeostasis, whether it be in the brain or wherever. I mean,

01:47:57.000 this is just sort of making you as if you were genetically one of those gifted people that

01:48:02.260 tends to run a nice low cholesterol. Well, that's interesting. You know,

01:48:05.620 that's sort of where I've migrated almost. I'm a low-dose prevastatin plus PCSK9 inhibitor.

01:48:11.600 And I was thinking about doing the experiment of switching from prevastatin over to Zetia to see.

01:48:18.620 And the reason for me is I had a calcium score of 6 when I was 36. And that's in the presence of,

01:48:25.680 you know, all the exercise and stuff. Now, I would argue at the time my nutrition was horrible

01:48:29.640 because it was a quote-unquote traditional athlete's diet of a gallon of Gatorade a day or Powerade.

01:48:35.060 That's the old athlete's adage, you know, if you run the engine hot enough, you can burn any fuel.

01:48:40.440 But Peter, I would say, you said, you know, a calcium score of 6 when you were 36.

01:48:45.700 Despite your exercise, I would say maybe because, you know, when you're swimming 20 miles over,

01:48:51.040 you know, like you were hammering, hammering, and really intense exercise will accelerate coronary

01:48:56.840 calcification. Yes, I have actually thought about that. And I repeated the calcium score

01:49:01.720 in 2017. So that would have made me 44 or whatever. It was zero.

01:49:08.980 Wow.

01:49:09.820 Now, it's very interesting because, as you know,

01:49:12.940 That is super rare, by the way.

01:49:15.020 Yeah, well, and I talked about this at length with Bob Peters, who is,

01:49:19.600 I think Bob Peters and Steve Wolf are hands down the best cardiac radiologists in New York City.

01:49:24.480 Um, and you know, so I had, I had a, I had a CAC and CTA done with them, uh, incredibly low

01:49:32.220 radiation, by the way, 2.2 millisieverts for a CTA and CAC. And the question was, Hey, is it an

01:49:40.280 artifact? When you have a calcium score go from six to zero, are we just sort of missing it? Cause

01:49:45.600 there was still a little blip in the endothelium of the LAD in that 2017 study. It just didn't

01:49:52.120 register as a full calcium. So, so I'll probably go back in a year and just repeat the CAC because I

01:49:58.020 am curious. The point is like, even if there's a little calcium there, it's really, really unusual

01:50:04.740 for the calcium score to go anywhere but up. And usually it goes up like 25, 30% a year or more

01:50:10.980 with, with, with calcification. So it's kind of like we wish our investments, you know, like the

01:50:15.200 compound interest, you know, it, it really, it really can accumulate. But, and I'll have to say,

01:50:21.060 I've probably read 150,000 calcium scores in the last 20 years because, because, and we've probably

01:50:27.100 done 600,000 in our practice and we do 50 or 60 a day. So like you virtually never see that. And now

01:50:34.480 granted if at that low level, you know, you, you kind of nipped it in the bud with your better diet and,

01:50:39.760 you know, probably, you know, tapered your exercise. I don't know. But in any event,

01:50:44.720 I saw a distinctly unusual pattern of regression in a calcium score in a good friend of mine who's an

01:50:51.800 executive. We'd been on a statin for, you know, decades at a calcium score of like 1200. It had

01:50:57.100 been going up, no diabetes, but you know, he's obese. And we switched him over because he has some

01:51:02.760 eggs to a PCSK9 inhibitor and a Zetamide. And a calcium score a couple of three, three years later

01:51:08.200 had gone down from like 1200. I mean, from, no, it was like 1400, but it was like two or 300

01:51:14.260 lower, you know, more than the margin of error of the test that made me think, you know,

01:51:19.800 well, number one, statins do tend to increase coronary calcification, but I bet PCSK9 inhibitors

01:51:26.640 don't. And certainly that anecdotal experience, and I'll bet, I'll bet you a Zetamide doesn't either.

01:51:32.140 So I saw an abstract, but I don't know if it ever made it to publication that actually

01:51:36.120 suggested PCSK9 inhibitors decreased calcification.

01:51:40.240 That was my anecdotal experience.

01:51:42.300 Yeah. Now, of course, I don't know what that means because in the end, I don't typically

01:51:48.060 re-scan patients. If I have a 50 year old who shows up with a calcium score of a hundred,

01:51:52.100 I have all the answer I need to know, which is we need to be way more aggressive. And there's

01:51:57.280 nothing I'm going to glean by re-scanning you next year to find out you're 120 versus 80. It will not

01:52:03.800 change our management.

01:52:05.060 And it just discourages, you know, somebody who's doing their best.

01:52:07.760 Yeah.

01:52:08.040 It's very discouraging to think, and then you have to explain, well, you're on a medication

01:52:11.540 that does accelerate it, but it reduces your risk despite that because it's making the plaques

01:52:15.620 less prone to rupture. And I'm the same way. I rarely, the only time I increase in is people who

01:52:20.520 aren't doing the right thing. They're not taking their medications or they're still smoking or they're

01:52:25.140 not exercising. And then I'll check and say, you know, it's gone up from a thousand to 1300 or a

01:52:30.180 hundred to 200, you know, you need to get on this. But the dirty little secret is that it goes up in

01:52:35.160 most people, but nonetheless, we can prevent cardiovascular events with all these strategies

01:52:39.840 we're talking about, despite the coronary calcium.

01:52:42.360 I'm so happy to hear about what you're doing. A $50 CAC really at that point, when you can get that

01:52:49.560 level of a diagnostic test for less than the cost of a nice dinner, there's really no barrier to

01:52:55.120 entry. And then those people that have a positive score, we get them over in our cardiometabolic

01:52:59.660 clinic, our cardio wellness clinic. We have two different clinics, one focusing on the glucose

01:53:04.160 side of things and, you know, the SGLT2 inhibitors and the GLP-1 agonists and metformin and weight

01:53:09.560 loss. And the other one on is just standard risk factors of lipids and whatnot. But we get them

01:53:13.660 plugged in and we see them two, three times a year. We make sure they're, you know, there's nothing

01:53:17.500 like feedback, right? I know you're a big fan on getting lipids tested and test these various

01:53:22.980 markers, HSCRP, A1C, you know, a lot of things that we follow because when you know better,

01:53:30.360 you do better and people need feedback. To round out our discussion on the pharmacologic

01:53:35.440 tools, where are you on the high doses of EPA versus EPA, DHA combined? Obviously, these are

01:53:41.840 becoming very popular tools in the toolkit. Again, just at the pharmaco level, also at the supplement

01:53:48.200 level, if you pick your supplements right, how do you think about these in terms of heart health and

01:53:52.140 brain health? So again, you know, super enlightened question. And this is like one at the crux of

01:53:58.560 some of the most exciting stuff going on right now. So omega-3, like we're talking about some other

01:54:03.900 nutrients, we're eating like maybe an order of magnitude less of that than what we did in our

01:54:10.400 evolutionary experience. Some people argue, you know, when we get access to shellfish and seafood is

01:54:16.060 when our brain expanded, you know, three or 400,000 years ago. So the omega-3, you know, like

01:54:21.620 20% of the dry weight of the brain is polyunsaturated fats, and its favorite polyunsaturated

01:54:28.040 fat to plug into those membranes in the neurons is a DHA. EPA is also, you know, another super

01:54:35.080 important omega-3. And a lot of my patients come in and they stop their official, they stop their

01:54:41.100 omega-3 because their doctor told them, oh, no, these don't work. And as you pointed out many times in

01:54:46.460 your writings and whatnot is even randomized controlled trials can be wrong, can be large

01:54:50.800 and wrong if you're testing the wrong people, if you're using the wrong dose. And a lot of those

01:54:55.140 trials were done with small doses. And these big meta-analyses, not to mention the REDUCE-IT

01:54:59.740 study, which recently tested the four grams of EPA and people that had heart disease or diabetes with

01:55:05.740 other risk factors, you test it has triglycerides above 150. So you test the right people, give them a nice,

01:55:11.180 robust dose, and you see these spectacular results from a nutrient. And a lot of the reasons doctors

01:55:17.860 dismiss it is because, again, we don't get taught anything about nutrition. We have an inherent

01:55:22.220 distrust that anything doing diet or supplements is worthless. And that is so untrue. And omega-3 is

01:55:29.500 exhibit A. So the latest meta-analysis, there was one just out in Mayo Clinic Proceedings coming out this

01:55:35.760 coming week. I wasn't on this, but one of my best friends was Chip Levy from down in Ochsner. This is

01:55:41.460 done with some Italian collaborators, but it's a really good meta-analysis of all the randomized

01:55:45.780 data with omega-3. And they show for every gram per day of EPA, DHA taken, you reduce risk of MI,

01:55:55.920 cardiovascular death, and even trends towards all-cause mortality. But the point is, like a lot of

01:56:03.020 studies just use one gram, but if you use two, three, four grams, you see these really remarkable,

01:56:08.060 like in the REDUCE-IT study, 25% to 30% reduction in cardiovascular events and all-cause mortality,

01:56:14.940 even in people, especially if they have triglycerides above 150. The question about whether

01:56:19.460 it's EPA versus DHA, you know, the evidence in that trial was EPA. But if you look at the meta-analysis,

01:56:25.920 you know, as long as you're getting that dose of EPA and DHA, I mean, I think it's important to have

01:56:30.200 some DHA in the supplement too, just because, again, it's important for the membranes. And

01:56:35.480 our evolutionary experience would suggest we weren't just using EPA, we're using the combination.

01:56:40.980 I'll tell you, I agree with you completely on that. And this is, I put this in the category

01:56:44.340 of things I can't wait to learn. I mean, sometimes I just get excited about the state of natural

01:56:48.880 knowledge and how it continues to evolve. And I can't wait to see five years from now what we know

01:56:53.800 on this question, because I was a bit surprised by the combined EPA-DHA trial. I really expected that to be a

01:56:59.340 favorable response, especially in light of what we saw in the four-gram EPA-Vicepa trial. So again,

01:57:08.380 we just have to see where this thing goes. But I agree with you.

01:57:11.300 That was the strength trial you were talking about.

01:57:13.480 That's right. That was halted early. Yeah.

01:57:15.780 So it might be that four grams of EPA in that concentrated form is the way to go

01:57:20.660 in a super high-risk person for cardiovascular disease. But a combination of EPA and DHA through food,

01:57:27.420 oily fish, as you said, might be what's conferring the real benefit. That's how we got it in nature.

01:57:32.900 I think the broader question always comes to, is there a harm of higher doses of EPA and DHA?

01:57:41.000 And I feel very confident now that the answer to that question is no. Provided you're getting

01:57:45.840 your product through a clean source, I think the answer is no. And so we have zero affiliation with

01:57:53.360 any companies that produce any of these products. And we had a third party do a validation of

01:58:01.460 Carlson's, which is the one that we have preferred for our patients. And we found it to be pure,

01:58:08.060 without contaminant, and it contained what it said it contained. So I'm always happy to pay that

01:58:14.040 little bit of a premium for that product to at least get an over-the-counter version that's good.

01:58:19.600 So I don't have to sort of fork over for a prescription version.

01:58:23.260 Yeah. I'm the chief medical officer for a company called Cardiotabs. I don't get paid

01:58:29.000 anything from them, but that's kind of my goal with them too. And we also source it from Norway.

01:58:35.160 They know more about purifying, concentrating, detoxifying omega-3 than anybody in the world,

01:58:41.140 as far as I'm concerned. And usually go over to Scandinavia there and visit with the leaders in

01:58:44.920 that just to see what their latest and greatest stuff is. But yeah, this is a food. And I think

01:58:50.340 it's super important, not only for cardiovascular health, but Peter, the latest data on mental health

01:58:56.020 is really important. Again, this is a fundamental component of cell membranes that most Americans,

01:59:01.700 upwards of like 90% of Americans aren't getting enough omega-3 in their diet. And it correlates with

01:59:07.380 depression, ADHD, suicide, cognition, dementia, all those things. I mean, this is like a super easy

01:59:15.220 way to markedly improve mental health. My wife, Joan, is constantly harping on this, that there's

01:59:21.200 all this violence and suicide and depression. And the basic thing to do is take a nice high dose of

01:59:29.580 omega-3 every day. It's harmless, it's cheap, and it has profound benefits. And lots of times you can

01:59:35.200 keep people off of antidepressant medications. That and a well-absorbed curcumin with high-dose

01:59:42.480 omega-3 is as good or better than any antidepressant out there. And they also help to improve brain

01:59:48.380 function. And again, your doctor won't prescribe these, but these are very, very effective ways

01:59:53.700 to improve mood, cognition, and probably reduce dementia in the long run. We have a paper coming

01:59:59.320 out I sent you a copy of in the Journal of Alzheimer's Disease showing that a highly absorbable

02:00:04.580 curcumin, theracurumin, in a randomized trial. The study was a TNF-alpha inhibition for preventing

02:00:11.680 dementia. And TNF-alpha, as you know, is this master hormone of inflammation. And there's some really

02:00:17.600 fascinating, which we outlined in this sort of systematic review, that the biologics that reduce

02:00:23.240 TNF-alpha, like a tanorecept, is the best one. It's a decoy receptor for TNF-alpha. And so it reduces

02:00:31.060 inflammation. And there's multiple big studies of millions of people in databases, that's all

02:00:36.940 observational data, but that it reduces risk of Alzheimer's disease 60 to 70%. Now, those are

02:00:42.140 expansive biologics that sometimes can cause serious side effects. But curcumin is the active

02:00:47.180 ingredient of turmeric. And if you use a highly absorbed one, you get some pretty impressive

02:00:51.220 reductions in TNF-alpha that have been correlated in small randomized trials with reduction. And there's

02:00:57.540 good animal models on this too. I mean, it's one of the most exciting things to me right now is I

02:01:01.800 really think this is easily the most exciting thing ever for maintaining cognition, preventing

02:01:07.780 Alzheimer's disease. And it still needs to be fleshed out, but there's some very good biological

02:01:12.780 plausibility behind it and some fascinating animal data, human data, and even some small randomized trials.

02:01:20.000 You know, working with Richard Isaacson, who I've interviewed for this podcast, and I'll be

02:01:23.680 interviewing again shortly. We've sort of put together our in-house kind of playlist for basically

02:01:30.400 once we identify patients that we deem high risk for Alzheimer's disease, which we define as age over

02:01:36.060 60, a relative that has a history of Alzheimer's disease, or at least one copy of an APOE4 gene,

02:01:42.420 or some other gene such as an anti-TNF gene, or TOM40, or one of these other genes that tends to

02:01:49.740 be associated with Alzheimer's disease, plus or minus APOE4. We just have sort of a full court

02:01:55.260 press approach. And one of the things on that list is indeed theracumin for exactly the reasons you've

02:02:00.420 stated. I became pretty impressed with those data about two years ago. And so I was excited when you

02:02:05.240 sent over that manuscript last week. So you noticed that Richard Isaacson was a co-author on that paper,

02:02:10.800 as was Gary Small from UCLA, who's, in my opinion, those guys are two top brain scientists in the

02:02:18.120 country for, you know, things like preserving cognition. So yeah, I mean, I think that the

02:02:22.820 people who are best informed on that would agree with you on that approach. You know, I guess closing

02:02:28.840 thought, James, is I'm just impressed by the breadth of your sort of curiosity and obsession. You know,

02:02:36.780 again, interventional cardiology is a niche sport, right? It's a, you know, you're a cath jockey at that

02:02:44.100 point. And you sort of left that behind and the world has become your oyster, so to speak. And

02:02:50.580 you're now interested in the role that theracumin can play in inhibiting tumor necrosis factor in the

02:02:57.440 development of dementia. I mean, do you ever kind of look back and reflect on the journey of your

02:03:03.040 career? I'll pause there before asking another question. I just followed my heart and what I was

02:03:09.700 most interested in. And I like to joke that, I mean, I'd be doing the same thing right now if I wasn't

02:03:15.320 getting paid. I mean, I love what I do. And I think of life as, you know, like this gift of we have our

02:03:21.480 time here on earth, and it's about like helping others and, and making a positive difference. And I'm just

02:03:27.340 so grateful that we live now where, where we have all these tools. And like you say, it's just so

02:03:33.200 exciting. There's all this emerging data for people who are trying to pay attention. It kind of like that

02:03:38.460 line from Dickens was, it was the best of times. It was the worst of times. You know, there's a lot

02:03:43.360 of people out there that, you know, suffering from all sorts of terrible things. A lot of it's

02:03:48.240 lifestyle related, and it's not their fault. I mean, it's like this whole world is set up to

02:03:52.240 minimize activity and maximize calorie consumption. But there's also people who are paying close

02:03:57.740 attention. And, and we have all these powerful tools and, and use this information to help each other

02:04:03.480 and to live not only longer, but more sort of active and fulfilling and enjoyable lives. So

02:04:09.540 to me, it's, it's just a blast. My last question then James would be,

02:04:14.160 if there's somebody listening to this, who wants to go into medicine and feels, or is in medicine for

02:04:20.200 that matter, and kind of feels the same conviction you do, which is the real answer is in preventing

02:04:25.680 disease. And whether that's their passion is in cancer or cardiovascular disease or neurodegenerative

02:04:30.960 disease, diabetes, whatever the case might be, you know, you said it at the outset, nobody's

02:04:36.220 reimbursing really for prevention. You've got to kind of create your own path. What would your advice

02:04:42.400 be to somebody who wants to become a preventative oncologist, a preventative cardiologist, a preventative

02:04:51.340 neurologist? How would you advise them to craft their way?

02:04:54.980 Well, that's, that's a difficult question, but I can just tell you that it doesn't have to be

02:05:00.600 all or nothing, you know, even like the calf jockeys, like they say, you know, some of my

02:05:05.440 partners are, we are calf jockeys who are very enlightened about lipids and, and, you know,

02:05:09.920 don't necessarily have to do it all the time, but you need to be able to be well versed enough to

02:05:14.100 strongly endorse it. And I mean, I'm in a big group of 65 cardiologists with, you know, another 50

02:05:21.120 nurse practitioners or physician's assistants. And so I can kind of carve out that niche and live

02:05:27.820 there most of the time, although I'm still around in the hospital and that sort of thing. But in the

02:05:32.180 future, this is going to be an increasingly important part of medicine. People are going to

02:05:36.420 understand, you know, they'll pay a lot to have their life optimized, not only for longevity,

02:05:42.840 but also for enjoying life and being fully functional. And I think there's never been a

02:05:49.100 time, a better time to, you know, get interested in prevention. It's just, it's, it's a lot of blue

02:05:53.360 sky out there and a lot of promising therapies and lifestyles and strategies that we can deploy now.

02:06:01.320 I've enjoyed this discussion immensely, as is the case with virtually every podcast. I learn at least

02:06:06.800 one thing. And in this one, I've learned many things that I can't wait to take back to

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The Peter Attia Drive - October 26, 2020

#134 - James O'Keefe, M.D.： Preventing cardiovascular disease and the risk of too much exercise.

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