The Peter Attia Drive - #276 ‒ Special episode： Peter answers questions on longevity, supplements, protein, fasting, apoB, statins, and more

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

00:00:16.580 my website, and my weekly newsletter all focus on the goal of translating the science of longevity

00:00:21.580 into something accessible for everyone. Our goal is to provide the best content in health and

00:00:26.780 wellness, and we've established a great team of analysts to make this happen. It is extremely

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00:00:53.260 of the subscription. If you want to learn more about the benefits of our premium membership,

00:00:58.080 head over to peteratiyahmd.com forward slash subscribe. Welcome to a special episode of

00:01:06.800 The Drive. This is an episode that is set up like an AMA where Nick is asking me questions. However,

00:01:13.560 this will be an episode that is available to everyone. Where this differs from most AMAs is

00:01:19.640 that in this episode, I haven't seen the questions beforehand, and I come in kind of blind. As

00:01:24.780 such, whereas most AMAs go an inch wide and a mile deep, here we go, I would say, a mile wide and a foot

00:01:32.680 deep. For this conversation, the team pulled some of the most common questions that we are asked,

00:01:37.660 including some that I traditionally can't stand answering. Of course, I have no choice here,

00:01:43.080 and therefore we go through those in today's podcast. We end up talking about why I don't think

00:01:48.140 people are currently going to be able to live to 120, 150, or 180, some of the claims you see out

00:01:53.560 there all the time. We talk about what supplements I take and why you shouldn't just blindly follow me

00:01:58.580 by taking the same thing. We talk about how to lower your ApoB with and without medications.

00:02:03.960 We talk about how I think about taking statins over a long period of time and what we know about other

00:02:09.240 ASCVD-modulating drugs today or in the pipeline. We talk about why there's no such thing as good or bad

00:02:15.400 cholesterol, why nutrition research is so hard, how I think about the question of, quote,

00:02:20.820 what is the best diet, how I hit my protein targets throughout the day, what my current

00:02:26.100 favorite wearable is, and what the role for CGM is in non-diabetics, and much more. If you're not a

00:02:32.680 subscriber, this episode will hopefully give you some insight into our AMAs, although as mentioned

00:02:37.780 earlier, the format here is a little different. Without further delay, please enjoy this special

00:02:42.860 episode of The Drive. Peter, welcome to a special podcast. How are you doing?

00:02:52.580 Doing pretty good. Good. So today's episode, we're going to do something a little different.

00:02:57.540 It's going to be kind of like an AMA style where you're the one answering questions,

00:03:01.780 but it's going to be an episode that's available to everyone. We've done this a few times in the past,

00:03:07.060 usually our Strong Convictions loosely held episodes celebrating the 100, 200 episodes.

00:03:13.560 Those just receive really good feedback. And so what we decided to do was do another type of those

00:03:19.740 episodes, but instead pull some of the most frequently asked questions that have come through

00:03:25.060 the site. And so we organized them a little bit by various topics, but this is going to be an episode

00:03:31.360 that's kind of more old school style where it's just question answer. A lot of these questions you

00:03:38.120 haven't seen before, which is probably good because some of them you've always refused to talk about

00:03:44.060 on AMA, such as what supplements do you take? I know it's not your favorite subject to go into those

00:03:50.760 details. So we're going to get into them today, which I think will be good. And I think it should just be

00:03:56.080 a fun conversation where you're coming into this blind and it should be really interesting,

00:04:01.920 I think for the listener and viewer. So with that said, anything you want to add before we get

00:04:07.780 started? Why do people care what supplements I take? We can save that for the question. We will get to

00:04:14.140 it. And I think people will find it enjoyable. The other thing I should say is, do you know why

00:04:19.460 I'm also excited to have this conversation today of all days with you? No. As our friend Kyler

00:04:25.920 Brown would say, based on some emails we've exchanged earlier, you kind of seem like you're

00:04:30.580 in a spicy mood today. So I think it's going to be kind of fun to go through these questions. What

00:04:36.120 do you think? I think I am in a very spicy mood. So for the listener and viewer, this should be a fun

00:04:43.620 one all around. With that said, first question, when people think of longevity, a lot of times in the

00:04:50.500 space, they think of living to 120, 150, 200 years old. I think anyone who's listened to your podcast,

00:04:59.880 read the book, listened to interviews you've done, you're not really in that camp of very confident

00:05:05.500 that we're going to live to 120, 150 years old. One of the common questions we get is just,

00:05:10.580 why is that? Why do you think that's maybe not possible? And the follow-up would be,

00:05:16.060 based on that, why do you think it's important to act and live like we might only get to 90 years

00:05:23.460 old? This is a bit of a complicated question. So why do I not have confidence in the biohacking

00:05:31.020 your way to 120, 150, 180? I've heard all of these sorts of numbers. Because I don't think we have

00:05:39.300 the tools to address the underlying aspects of the aging of biology that are relentlessly pushing us

00:05:49.600 towards the end of our lives. Again, that's not a depressing statement. I think it's just an obvious

00:05:54.720 reality, right? So there are things about us as we age that we have the capacity to reduce the rate

00:06:02.920 of change on. We can slow them down. But I've seen no real evidence that we can reverse them in a

00:06:10.180 meaningful way. Now, it's true that there are some people out there claiming they've got their aging

00:06:16.920 clock and it shows that even though their birth certificate says they're 60, they're really 35.

00:06:22.820 We could put some time into explaining why that's not correct. So the long and short of it is,

00:06:28.060 we don't have any evidence that we can take the diseases of aging and erase them or that we can

00:06:35.240 take the underlying processes of everything from defects in mitochondrial function, defects in protein

00:06:45.760 folding and misfolding, changes in DNA breaking and repair, breakdown in nutrient sensing, all of these

00:06:53.260 pathways. I haven't seen any evidence that we can undo that. So then what would you have to believe?

00:06:57.460 So if you're going to believe someone my age, i.e. someone who's 50, is going to be around in 70

00:07:04.560 years, you have to believe that in the next dozen years or so, someone is going to come up with a way

00:07:13.240 to completely halt aging and or reverse it. In other words, it's not going to do me any good if this

00:07:19.860 happens 50 years from now, because in 50 years, I probably won't be here. And I spend a lot of time

00:07:25.200 looking at this type of literature. I really do spend a lot of time looking at this technology.

00:07:31.300 I haven't seen many examples where there's a bigger mismatch between what is actually happening

00:07:38.340 scientifically and what is being talked about in the press, on social media, on podcasts. And that chasm

00:07:45.940 is enormous. In other words, what's really happening is like nowhere near the sci-fi that's being

00:07:52.740 portrayed. So because of that, and because I have confidence that what's actually happening is more

00:07:59.820 a representation of reality, I know that these things are not a decade away. That's why I take

00:08:06.120 that point of view. Now, why does all of this matter? I think this matters because if you knew

00:08:12.160 that this was as good as it was going to get, and I don't think it is, by the way, I do think there

00:08:17.240 are incremental things that are going to make a difference, even in the lives of people my age.

00:08:22.540 But if you thought that, look, this is directionally as good as it were going to get,

00:08:25.960 I think it would motivate you to be more serious about using the tools that we have today for primary

00:08:33.880 and secondary prevention of disease, for optimizing and maximizing lifespan and healthspan.

00:08:39.880 If for no other reason, you would do that as a hedge against the enormously long odds that something

00:08:47.740 dramatic and miraculous is going to happen in the next decade or two.

00:08:52.600 To double click on a few things there, when you were talking early on about diseases,

00:08:57.180 were those diseases what you call the four horsemen from your book? Is that what you're referring to?

00:09:01.880 Yes. You still have to have a strategy that says, how are you not going to die of ASCVD,

00:09:09.180 cancer, neurodegeneration, dementia, and of all of those diseases, the only one where I can see a

00:09:15.980 pretty clear path to delay it significantly would be ASCVD if you take really dramatic steps early in

00:09:25.160 life. Instead of talking about what we think of as primary prevention, think of ultra-primary

00:09:31.680 prevention, treating people in their 30s, making sure a person never, ever walks around with an ApoB

00:09:38.640 over 30 or 40 milligrams per deciliter, making sure a person doesn't even spend one year with mild

00:09:45.420 hypertension, making sure a person is always metabolically healthy. If you do that, I agree,

00:09:50.840 you would not get atherosclerosis in a normal lifespan. But we don't have that degree of certainty

00:09:57.340 for pushing off cancer indefinitely, for pushing off neurodegeneration indefinitely, for pushing off

00:10:03.660 dementia indefinitely. Nor do we have it, by the way, for pushing off, I think, sarcopenia

00:10:10.200 indefinitely, or pushing off arthritis indefinitely. I mean, there's these other conditions that are

00:10:15.960 not as interesting to think about because they don't rise to the level of the horseman,

00:10:20.000 but they matter a lot. So physical frailty is a really, really, really big one.

00:10:24.280 If you manage to not die of heart disease, cancer, neurodegeneration, dementia,

00:10:30.340 and you're willing to train really hard, I really do think there's a path to be physically robust

00:10:36.400 as a centenarian. But I don't see a path to doing that at 120 or 150, unless there is a significant

00:10:45.100 technologic breakthrough that would basically allow us to rewind. And maybe this is a different

00:10:51.620 discussion, and maybe it's a longer discussion, Nick. And I don't know if we want to go into it

00:10:55.180 because it's taking us a little off topic, but it really gets into what does it mean to age at a

00:11:00.120 cellular level? What is the role of the epigenome in regulating our genetic code? I don't know if

00:11:07.000 there are other questions about that topic, but we could certainly defer to that.

00:11:10.500 On that topic, I know that's talked a little bit about in the episode with David Sabatini,

00:11:15.620 Matt Cabral, and so maybe we'll pull questions from there and do a future AMA kind of diving into that

00:11:21.520 a little deeper. Kind of what I'm hearing you say is, you still think that we will succumb to the same

00:11:28.080 diseases that will kill us. Your goal with Medicine 3.0 and Prevention is still to put that off as far

00:11:35.040 as possible, but that doesn't mean you're going to put it off until you're 120 years old. The goal is

00:11:41.420 to really live as robustly as possible and avoid those as long as you can, but still more in the

00:11:47.300 traditional lifespan opposed to the 150 year old lifespan. I think that taking all of the steps

00:11:54.120 that I talk about in the book and could seriously add a decade to life. I don't doubt that you can

00:11:59.600 live a decade, a decade and a half, maybe two decades longer. I don't doubt that, but I don't think

00:12:05.840 we're talking about adding 30 years or 50 years to lifespan. What I think is more important is that

00:12:12.580 whether you're adding five years, seven years or 10 years to your lifespan, what I think is much more

00:12:19.020 interesting and much more important is reducing or compressing the period of morbidity late in life.

00:12:29.240 What I think people should fixate on is how do I not be really, really frail, both physically and

00:12:38.520 cognitively in the last decade of my life, what I call the marginal decade. I don't know if I'm going

00:12:43.020 to live till I'm 85 or 90 or 80 or whatever. I mean, I don't feel like I have as much control

00:12:49.020 over that. I think there are some elements of bad luck that factor into that. What I feel like I have

00:12:53.920 much more control over is when I'm in my marginal decade, can I still go for a ruck? Will I carry 80

00:13:01.520 pounds on said ruck? No way. But I might be able to carry 10 or 20. Will I be able to swim half a mile

00:13:08.900 in a pool? Yeah. Will I be able to swim it as fast as I can now? No chance. But I could still swim half

00:13:15.760 a mile and get out of the pool under my own power. Could I sit on the floor? You know, it's all those

00:13:19.420 things that I talk about in the centenarian decathlon. Those are the things I think that we

00:13:23.160 really want to relentlessly fixate on. Because I think most people would rather live to 90 and die of a

00:13:29.680 heart attack while swimming in the ocean, but being otherwise in remarkable shape than live to 120 and

00:13:36.280 spend the last 30 years of that unable to do much. Earlier, you also mentioned there's incremental

00:13:43.860 things you think that could happen that will help someone, even your age at 50, live longer. Do you

00:13:50.160 want to just lightly touch on what a few of those things are that you were talking about there?

00:13:54.360 One of the most interesting, and I talked about this on a recent podcast with David Sabatini,

00:13:59.680 Matt Caberlin, is I still think we are really in early days of understanding what pharmacologic

00:14:07.060 inhibition of mTOR can do. There's really a lot of promise with this approach in virtually every other

00:14:14.680 model species outside of humans. And that doesn't mean it will work in humans, but it's very interesting.

00:14:22.160 And I think if we had better biomarkers, again, I think that's something that can happen in our

00:14:26.960 lifetime. I think that's a very promising strategy. And it's especially promising when you consider

00:14:32.080 that the animal models show that pharmacologic inhibition of mTOR using rapamycin or its analogs,

00:14:40.520 even applied late in life, still provided lifespan and healthspan improvement. And why that's

00:14:47.940 interesting is very few other interventions that have shown to be geroprotective work when applied that

00:14:55.820 late in life. So that to me is very promising. Last question on this aging topic would be,

00:15:02.260 let's take someone who's listening, maybe your age, but they have a son or a daughter who is 10 years

00:15:08.960 old. How do you think that 40-year time scale differs as you look at a 10-year-old's potential

00:15:15.560 lifespan today compared to your 50-year-old lifespan today?

00:15:19.560 That's a good question. I don't know. Look, I'm that guy, right? I mean, I have a six-year-old,

00:15:24.140 a nine-year-old, a 15-year-old, and I often think about what's the difference between me and them

00:15:30.760 in terms of their runway versus mine vis-a-vis the types of technologic breakthroughs that we're

00:15:36.940 interested in. And again, the one that I'm most interested in is probably on selective and high

00:15:44.940 fidelity, high-precision modulation of the epigenome. I don't know the answer, truthfully. I simply don't

00:15:53.220 have a way to predict the pace of that type of innovation. And of course, not to be a doomsdayer,

00:16:01.220 but even though they have a longer horizon for good things to happen, they also have a long horizon

00:16:07.060 for bad things to happen. And when I think about bad things that can happen to our kids,

00:16:13.500 of course, you can't help but think about nuclear war. By the way, in order, how would I rank them?

00:16:19.180 I don't know. Probably I would say biological terrorism would be the single greatest threat

00:16:24.220 to our species simply based on the low barriers to entry and the ease with which there's proliferation.

00:16:31.100 But again, you could sit here and debate what's the greater threat to our species. Is it nuclear war?

00:16:35.780 Is it climate change? Is it biological warfare? The point being here, they have just as much

00:16:41.180 time to be exposed to really bad things that could obliterate our species as good things that could

00:16:46.660 extend the life of our species. So I just don't know how to handicap the pros and cons on that.

00:16:52.200 That could be our next book. We could call it The Fifth Horseman, and it could be all about that.

00:16:58.480 That's a good intro into this next section, which gets into drugs and supplements and the most common

00:17:04.700 questions we get asked there. But I think you mentioned one thing in the aging section that I

00:17:09.760 think would be worth touching on real quick. I think it will affect what we talk about here, which is

00:17:14.180 we really don't have biomarkers for aging. And you've been open about frustrations with that because

00:17:21.520 when you look at geoprotective molecules and you look at if these things are working or not,

00:17:28.160 we really don't know because we don't have those biomarkers. So do you maybe want to talk about that for

00:17:32.620 just a minute to kind of set the stage? So when people hear you're framing for everything else,

00:17:37.780 I think it will make a little more sense. I think one of the most important things to understand

00:17:42.920 when you're using some sort of intervention is, do you have a biomarker to know if you're doing it

00:17:50.340 correctly? So think of like really basic things that most people don't even consider as interventions

00:17:55.540 like nutrition. How would you know if you're eating too much? Do you have a biomarker for it?

00:18:02.040 Sure. There are lots. One biomarker might be your weight. Another biomarker might be your waist

00:18:09.920 circumference. Another biomarker might be your insulin level, your glucose level, your average

00:18:16.500 glucose. I mean, you get deeper and deeper down this and you start to realize that how much you eat,

00:18:22.460 you have a way of getting feedback from the system that tells you, do you need to correct this?

00:18:28.660 The same is true for exercise. The same is true for sleep. So there might not be a lab value that is

00:18:37.620 specific to sleep, but there are clearly ways to get feedback to know if you're sleeping too much or

00:18:43.440 not sleeping enough. If you think about it through the lens of taking exogenous molecules, you take a

00:18:49.560 drug like lisinopril, an ACE inhibitor for lowering blood pressure. How do you know if you're taking the

00:18:56.920 right amount? You measure your blood pressure. Let's say you get started on a dose of lisinopril

00:19:02.540 when you're starting blood pressure was 135 over 85, and all of a sudden it's 115 over 75. That says

00:19:11.640 the drug is working. Are you symptomatic? By the way, that's another biomarker in a sense. No, you're

00:19:17.060 not lightheaded. Great. Everybody wins the game. If your blood pressure goes too low and or you're

00:19:22.720 symptomatic, which is probably the bigger issue, then you're taking too much. You have to dial the

00:19:27.240 drug back. If you're taking the drug and your blood pressure comes down but doesn't come down

00:19:30.660 enough, that's more feedback. Dial the drug up. So you have this sort of input-output ability with

00:19:36.460 every drug that we like to think of. Again, the same is true with drugs for diabetes, with drugs for

00:19:41.900 lipids, with cancer drugs that you take. You would be able to look and study, is the tumor shrinking?

00:19:47.580 Is the tumor growing? So you have somebody getting feedback. Well, the problem when it comes to

00:19:51.940 gyroprotection, this broad category where we are not targeting diseases specifically, but instead

00:19:58.280 we're targeting the underlying mechanisms of aging, is we can't measure it. We don't have a way to

00:20:06.640 measure it. So we take a drug, we take a supplement that we believe is gyroprotective, and we don't know

00:20:14.480 if it's working. Are we taking enough? Are we taking too much? Maybe if you're really lucky, you might find

00:20:19.780 a side effect that tells you you're taking too much. But do we really want to be in the game of

00:20:24.340 pushing things to the point of seeing overt side effects? So that's why I believe as unsexy as the

00:20:31.360 world of diagnostics and biomarkers are, and it is a very, very unsexy world. I mean, this is not a place

00:20:39.160 where people like investing money. This is not a place where there's an enormous amount of capital being

00:20:46.060 thrown at the problem. It is a very important problem, and it's going to be very important in

00:20:51.080 humans if we're interested in studying gyroprotection. Probably the very first time I went on kind of a 0.65

00:20:57.780 long diatribe on this was back when I was really, really obsessed with trying to understand the

00:21:03.200 perfect routine for fasting. I'm sure you can recall this circa 2018, 2019, 2020. I was very frustrated that

00:21:10.900 as much as I was trying to study this in myself and doing every sort of blood analysis under the

00:21:16.940 sun, I had no way of knowing if my fasting protocol of seven to 10 days of water only once a quarter,

00:21:25.060 three days once a month, was that too much? Was that too little? Was that doing anything? No idea.

00:21:31.720 To this day, I have no idea if that provided any benefit at all. I could certainly point to some

00:21:37.340 negative things it did. It cost me probably 20 pounds of muscle over six years, but maybe that

00:21:43.360 was a worthwhile trade-off given some other benefits, but how would I know? Don't know what

00:21:47.280 the benefits are. Don't know how to measure it. It's a very important problem, and it's one that I

00:21:52.100 hope more and more resources will be poured into because otherwise it's going to be very difficult

00:21:56.760 for us to move further in understanding what works in humans. On that, I do actually have another

00:22:03.920 framework question, which before we get to the list of supplements, which I know people are anxious to

00:22:09.180 get to, you've often talked about your analogy of, are you picking up a gold coin or a penny? Are you

00:22:14.560 picking up in front of a train or a tricycle? And oftentimes when I've heard you use this, it's a lot

00:22:20.360 of times as it relates to interventions, specifically drugs and supplements. Do you maybe want to quickly

00:22:26.240 give people what that framework is? Because I think it is really important based on everything you said,

00:22:31.520 which is a lot of this is kind of a guessing game and we don't really know. So we kind of need to

00:22:36.780 anchor it to another framework to try and figure out what are the risks and what are the potential

00:22:41.800 rewards as we try and figure out within ourselves, what are we willing to do and not do? It's nothing

00:22:47.760 more than a very simple matrix of risk and reward, which I'm sure anybody would easily be able to walk

00:22:54.500 themselves through. All I do is just to make it easy to remember. I just put very obvious concrete

00:23:02.180 examples in the corners of the matrix. So it doesn't matter which axis is horizontal or vertical,

00:23:08.380 but if you just say that the horizontal axis represents risk going from low to high and the

00:23:16.380 vertical axis represents reward going from low to high, you would say, okay, at a very extreme level,

00:23:24.460 low risk is bending down in front of an oncoming tricycle. And as you move from left to right on

00:23:31.060 that horizontal axis, it goes to jumping in front of a train track and grabbing something and then

00:23:36.120 getting off the train track. So that's going from low risk to high risk. And in terms of reward,

00:23:41.440 you would think of a penny being pretty low reward. And you'd think of a big fat juicy gold coin being

00:23:49.480 very high reward. So as you go from higher risk, you would expect and demand higher reward. So I'll

00:23:59.000 tell you a story. I'm embarrassed to say this because it speaks to just how stupid teenage boys are

00:24:04.820 and how much of a miracle it is that our species still exists with the utter lack of judgment that

00:24:13.160 exists in the presence of young boys. So when I was in high school, one of our favorite games to play

00:24:19.800 was when we would get off the train, we would immediately jump under the train and see who could

00:24:27.080 lay the most coins on the train track and then get out as quickly as possible so that once the train

00:24:33.000 started rolling, you could see how many coins got flattened. Just think about the abject stupidity

00:24:40.060 of this game. Another game that was tragically very popular when I was young was playing chicken

00:24:47.560 in front of the subway in Toronto. Who could be the last guy out? And very sadly, the younger brother

00:24:56.220 of one of my friends in high school did not make it out. He was killed by a subway playing a stupid game

00:25:02.540 of chicken. Talk about incredibly high risk for no reward. So how do we apply that to interventions?

00:25:13.680 I guess we're talking about this through the lens of supplements. Well, I think we have to acknowledge

00:25:18.220 that there's a great uncertainty with many of these things. And therefore, we should ask ourselves,

00:25:24.120 how can we handicap the risk based on human data, animal data, safety data, efficacy data as far as

00:25:32.860 reward? And where on that matrix do we place this intervention? So if you're going to take,

00:25:40.260 I don't know, fill in the blank, some fancy supplement that some internet guru is telling you like he's making

00:25:48.340 his own proprietary blend of crushed bird feathers and testicular juice. Okay. I mean, do you want to

00:25:56.880 take that risk? Because it's hard for me to imagine the reward is really there. So one of the things I

00:26:02.480 will push my patients on is when they show me their laundry list of supplements, I walk them through a

00:26:08.480 framework about thinking through it. And one of them is, where are you on the risk reward matrix?

00:26:13.020 So with that said, let's get into Peter Atia's list of supplements that he takes. You can pick

00:26:20.800 whichever one you want to start with. For some reason, I hate talking about this only because

00:26:25.340 I noticed that it tends to show up online and it somehow becomes like, well, if Peter does this,

00:26:31.860 you should do this or something like that. And there's no context to it. And therefore,

00:26:37.320 nobody understands the rationale. Nobody understands the clinical history and all of those things.

00:26:43.020 So with that caveat, which I don't think matters, because I just, at the end of the day,

00:26:46.860 don't think people care. I think a lot of people just are sort of searching, but I take EPA and DHA.

00:26:54.040 So I take fish oil. Again, I'm happy to even state the brands that I take of these things because I

00:26:58.660 don't have any affiliation with any of these companies. And frankly, I like to give a shout

00:27:02.260 out to companies that I think sell good products. So I use Carlson's EPA and DHA. I can't remember

00:27:08.020 exactly which one I take. I can never remember their names. They're so convoluted. It's like

00:27:12.400 super EPA or something, but it is the highest EPA version that they have. So by taking four of these

00:27:20.120 capsules a day, I'm taking roughly two grams of EPA a day and probably a gram and a half of DHA.

00:27:28.780 The reason I take that much is I'm treating to a dose. I'm treating to a red blood cell membrane

00:27:36.740 concentration of EPA and DHA of about 12%. So that's a blood test you would do. You have a biomarker

00:27:43.080 that I can use to say, I'm taking too much. I'm taking too little. Here you go. I take vitamin D.

00:27:49.520 I'm sorry that I'm blanking on the brand. I can see the bottle, but I'm blanking on the brand. I take

00:27:54.300 5,000 IU of vitamin D. Why? Largely because this is one of those things where I think the risk is

00:28:02.340 insanely low. I think this is really a tricycle and I'm not sure what I'm picking up. I think it's

00:28:10.080 more than a penny. I definitely think it's less than a gold coin. It might be a $5 bill, but I'd

00:28:17.020 pick up a five. If I was walking down the street and there was a kid riding a tricycle towards me

00:28:19.920 and I saw a $5 bill, I would pick it up. I think that most of the studies on vitamin D have been very

00:28:25.740 poorly done. And we do need to do a podcast on this. Maybe this is something we could deep dive onto in an

00:28:31.560 AMA. So I won't get into it more now, but having looked very critically at the vitamin D literature,

00:28:37.180 which is insanely underwhelming, I think it is almost assuredly the result of very lousy studies

00:28:45.480 that add no value to our understanding of the problem. So the dosing has been wrong. The duration

00:28:52.260 has been wrong. The compliance has been wrong and the targeting has been wrong. Everything has been

00:28:59.400 blown. And so I would say, we truly have no idea. I take SlowMag, that is a brand, and I take two or

00:29:06.460 three of those every day. So that is a slowly and completely absorbed form of magnesium. All in all,

00:29:13.520 I'm trying to get up to about a gram of total magnesium or elemental magnesium in my system a day.

00:29:20.580 And I get that through, again, through SlowMag, through magnesium L3 and 8, and through magnesium oxide.

00:29:26.860 So I take all of those things. I take methylfolate and methyl B12. I use Gero as a brand. Again,

00:29:36.200 here we do have biomarkers. You can measure B12 levels, but more than anything, I'm measuring

00:29:40.620 homocysteine levels. That's why I'm taking methylated versions of those. And basically, I take these to

00:29:47.920 keep homocysteine below 9. That for me just means just taking one a day. So I take the standard dose

00:29:53.740 of that. They do make it in two strengths, and I take the lower of the two, in part because my MTHFR gene,

00:30:01.680 most of us have variants of MTHFR. The variants I have are reasonable at methylation. This is actually

00:30:08.700 an interesting change. I used to take 50 milligrams of B6 daily. I've now lowered that to three times a

00:30:16.240 week. We have seen some people who, when they take too much B6, can actually develop a sort of

00:30:23.140 neuropathy as a result of it. Though I've never experienced any symptoms from it, a little further

00:30:27.960 digging has led me to realize we don't need nearly as much B6 as I thought we did. So I've lowered that

00:30:34.400 to 50 milligrams three times a week. And it helps with the homocysteine. You just have to be careful

00:30:39.660 that you're not overdoing it. I take a baby aspirin a day. I think the evidence for the use

00:30:46.200 of baby aspirin in cardio protection is pretty weak. This is kind of a soft call. I don't think

00:30:55.040 there's an evidence-based reason why I should take a baby aspirin. And there's even some evidence to

00:31:02.780 suggest that once you get significantly older, unless your risk of cardiovascular disease is significantly

00:31:09.140 high, the benefits of it, which are clear. There's no doubt there are benefits of a baby aspirin, but

00:31:14.380 they're outweighed by the bleeding risks that are associated with aspirin use. In particular, if you

00:31:21.160 fall and hit your head, that becomes a bigger liability. Baby aspirin use falls in and out of

00:31:27.620 favor over time. Given that I am very young, relatively speaking, to these study populations and not really at

00:31:36.940 risk for a risk for a bleeding injury, I think of this as picking up like a dollar or two dollars in

00:31:42.260 front of a tricycle at this point. But again, I'm always happy to reevaluate the use of this and any

00:31:48.020 supplement for that matter in the presence of new data. That might be it for daytime supplements.

00:31:52.600 In the night, I take ashwagandha. I take 600 milligrams of ashwagandha. I recently switched to

00:32:03.800 the Solgar brand. I take two grams of glycine. I use the Thorne brand. I take magnesium L3 and 8, which I

00:32:16.100 just mentioned. I use the Magteen brand. By the way, anytime you're buying magnesium L3 and 8, just make

00:32:23.220 sure it has Magteen in it. So you could buy it from any different company, but they have to have the Magteen

00:32:28.820 proprietary combination because they're the only people that have the license to make L3 and 8.

00:32:34.280 Occasionally for travel, I will take Gero's phosphatidylserine. It comes in 100 milligram

00:32:41.500 capsules or gel caps. For some reason, I like the gel caps better. No idea if they're just more

00:32:47.920 quickly absorbed. I truly have no idea. If I'm really going to the trouble of taking it, I'm

00:32:53.620 presumably on a long flight where I'm trying to overcome a significant time zone. So I'll usually

00:32:58.620 take about 400 milligrams. That's a compound that's been tested readily up to 600 milligrams.

00:33:04.900 It's possible I'm forgetting something else, but I think those are my supplements.

00:33:09.180 Sorry, there's two others I take, but they're not in the cabinet and that's why. So I take Athletic

00:33:13.240 Greens in the morning. Disclosure, I am an investor in that company. I'm also an advisor to that company.

00:33:19.120 So I take AG1 as a green drink in the morning and I take a probiotic called glucose. I think it's

00:33:28.200 called glucose control by a company called Pendulum. So I take two of those in the morning

00:33:33.360 with my AG. That's kind of like the first thing I consume in the morning.

00:33:37.840 With those, just on the whole, just because you take them, not everyone should take them and you're

00:33:42.920 looking at your medical history. What percent of that, let's say the same drugs or the same

00:33:48.780 supplements in the same doses were you taking a year ago? How is this changing? Yeah. Yeah. So

00:33:54.460 that way, if someone listening to this down the road, here's it, they don't automatically just go

00:33:59.060 do the same thing. Yeah. So a year ago, I was not taking the Pendulum probiotic. That's something

00:34:04.000 I've only been taking for a couple of months and I'm doing an experiment there, which is looking at

00:34:08.740 average blood glucose. So the reason I'm taking this particular probiotic is I believe, having

00:34:15.140 looked at all of these probiotics, I think this is the most rigorously tested and validated probiotic

00:34:23.060 out there. And in a small but double-blinded randomized clinical trial, it demonstrated a 0.6%,

00:34:33.120 meaning 0.6 absolute percentage point reduction in hemoglobin A1c in people with type 2 diabetes.

00:34:38.940 And that was only in 90 days, which is pretty interesting. It also was associated with,

00:34:44.340 I would say more than associated with, it demonstrated and caused about a 30% reduction

00:34:48.860 in postprandial glucose A1c, area under the curve. So meaning when you gave people a glucose challenge

00:34:56.380 and then measured and plotted a graph of their glucose response and looked at the area under that

00:35:01.460 curve, the people who had been taking this Pendulum glucose control probiotic had a 30%

00:35:07.900 reduction in that, meaning they had become more insulin sensitive. And I'm a couple of weeks away

00:35:14.460 from doing a blood test on myself to see if I've had any improvement in glycemic markers in response

00:35:21.240 to that. I was not taking that a year ago. I was not taking ashwagandha a year ago. I had taken it a long

00:35:27.960 time earlier, but just came back to it, probably found a slightly more potent version of it.

00:35:32.420 I was taking a different brand of fish oil before. I had used Carlson's in the past,

00:35:39.680 had switched to Nordic Naturals. Now I've switched back to this. I find it to be just a slightly more

00:35:45.080 robust product. The Nordic Naturals ones, for some reason, every third bottle had a broken capsule in

00:35:51.280 it. And once a capsule breaks in the bottle, it just totally destroys the remaining of the capsules.

00:35:56.360 It was just happening too frequently. I was kind of aggravated by it. I don't think I was taking a

00:36:01.080 baby aspirin a year ago. I think again, that's something I've kind of done on and off over

00:36:05.200 periods of time and probably the same with vitamin D. It's possible I wasn't taking vitamin D a year

00:36:09.340 ago. Yeah. So it's not only the drugs have changed, but even like the B6 you mentioned,

00:36:15.340 the dosing has also changed. Right.

00:36:18.240 So then if we look at outside of supplements and we kind of look at drugs,

00:36:22.000 the most common drug we'd asked about would be rapamycin followed by metformin. And we won't

00:36:29.980 get into those too much here because of that podcast with David and Matt. And then also we

00:36:36.440 won't get into too much on metformin because you and Andrew did a journal club and you kind of focused

00:36:42.460 on metformin. And so just for time's sake, we'll kind of punt those to those other resources. But

00:36:48.460 outside of that, the question around drugs that we can ask the most is kind of within the ASCVD.

00:36:55.440 And you mentioned early, that's a disease that you think we have some chance to really stop it and

00:37:02.220 to really delay the onset of it if we take early interventions. And one of the most common questions

00:37:07.960 we get is how do you lower your ApoB and what's realistic with and without pharmacology?

00:37:14.680 Without pharmacology. So first of all, exercise has no meaningful impact on ASCVD risk factors

00:37:20.440 through lipoproteins. It does in other ways. But if you're just talking about managing lipoprotein

00:37:24.880 risk, it really comes down to pharmacology, hands down the most potent way to do it. And then nutrition,

00:37:31.220 a far less potent, but not insignificant way to do it. On the nutrition front, you're basically

00:37:35.860 have two levers to pull. You can dramatically reduce carbohydrates, which will lower triglycerides

00:37:42.060 and all things equal. The lower triglycerides, the lower the ApoB burden, because you have to

00:37:46.640 traffic fewer triglycerides with the cholesterol. The other way to do it is dramatically cut saturated

00:37:52.060 fat. In a high saturated fat diet, what typically happens in addition to an increase in cholesterol

00:37:57.520 synthesis is the liver through something called the sterile regulatory binding protein says,

00:38:04.040 I don't need any more fat brought in. I don't need any more cholesterol brought in.

00:38:09.200 So it down regulates LDL receptors. So it pulls fewer LDL out of circulation and LDL will skyrocket.

00:38:17.360 So the reverse is true. If you cut saturated fat, the liver is going to want more LDL coming in. It

00:38:24.260 will upregulate LDL receptors and pull more LDL out of circulation. So if you were on a really low

00:38:31.260 carbohydrate, really low saturated fat diet, you would indeed lower your ApoB. Would you

00:38:39.100 lower it to the levels that I think are necessary to make ASCVD irrelevant? Most people probably not.

00:38:47.040 And then would that be a diet that for most people is sustainable long-term? That's probably a very

00:38:52.400 individual decision. So for someone like me who has very low triglycerides, I don't go out of my way to

00:39:00.360 eat saturated fat, but I'm also not restricting it either. I'd say I probably am in line with where the

00:39:05.160 average person is. My ApoB at a baseline would still be, I don't know, 90 to 100 milligrams per

00:39:13.800 deciliter, which puts me at about the 50th percentile of the population. So that's my normal ApoB.

00:39:19.580 That's far, far too high for someone who A, has a genetic predisposition to ASCVD, and B, just somebody

00:39:27.740 who wants to take the one horseman that can be taken off the table and take it off the table. So

00:39:33.280 my target for ApoB is 30 to 40 milligrams per deciliter. Therefore, that would require

00:39:37.660 pharmacology. And so I take three drugs to do that. I take a PCSK9 inhibitor called Bropatha,

00:39:44.920 and I take a combo drug called Nexlizet, which is bempendoic acid and ezetimibe combined into a

00:39:51.380 single pill. And the mechanism of action of ezetimibe is that, well, not to get too technical,

00:39:57.660 but it blocks the Neiman-Pixi-1-like-1 transporter in both hepatocytes and enterocytes of the gut.

00:40:04.040 It prevents non-esterified cholesterol from coming back into the gut after you've recirculated it

00:40:12.260 through your liver and into bile. So it prevents you from reabsorbing your cholesterol. Of the three

00:40:17.760 drugs I'm taking, that's far and away the least potent. Bempendoic acid is a pro-drug. What that

00:40:23.820 means is by itself, it is inactive. So when you ingest it, it goes to the liver, it gets activated,

00:40:29.620 and there it is a cholesterol synthesis inhibitor. It acts on a different enzyme from statins. And

00:40:36.300 what makes bempendoic acid special, for lack of a better word, is that it only inhibits cholesterol

00:40:42.500 synthesis in the liver. Whereas statins, which are very potent inhibitors of cholesterol synthesis,

00:40:48.020 they do so throughout the body because they don't have this pro-drug trick. When the liver 0.97

00:40:53.340 senses less cholesterol, it increases LDL receptor expression on its surface and pulls more LDL out

00:41:01.980 of circulation. So that's how both statins and bempendoic acid work. They work indirectly.

00:41:06.460 The difference is bempendoic acid is less potent than a statin and more selective in that way.

00:41:12.360 So the combination of those three drugs will keep my ApoB negligible. And equally importantly,

00:41:18.520 there are no side effects associated with that for me personally. And again, when it comes to lipid

00:41:24.000 management, it's certainly one of my favorite topics. I always tell patients, we have tools today

00:41:28.520 that we couldn't even fathom 20 years ago. 20 years ago, if you needed to have your ApoB slammed,

00:41:35.500 there was only one way to do it, which was megadose of statins. I don't believe any patient needs to be

00:41:40.620 on a megadose of a statin today. We just have too many other tools. And I do have some concern about

00:41:46.660 megadose of statins because one, the efficacy curves show that statins hit their maximum efficacy

00:41:53.960 at about quarter dose. The curve for the efficacy of a statin looks like this. For example, if you look

00:41:59.840 at resuvastatin, you're getting 85% of its maximum ApoB reduction at 5 milligrams. Roughly 85%,

00:42:10.760 you hit the maximum. And by the way, it's a drug that is typically dosed up to 40 milligrams.

00:42:14.680 So once you hit 10 milligrams, there's no need to go any higher because all you're really doing

00:42:20.540 is buying side effects and you're getting very little in the way of increased efficacy. So we're

00:42:25.360 very quick to pivot patients off statins if we can't get great efficacy with no side effects at low

00:42:32.820 dose. On those drugs, including statins, let's say, if you can get the efficacy at the low dose,

00:42:39.160 oftentimes while people who are younger in their 30s, 40s, even 50s kind of reach out and say,

00:42:44.680 do you have any concerns about taking those drugs for such a long period of time?

00:42:50.540 Yes and no. I think it depends on the alternative. So I think that there are some people who kind of

00:42:57.220 poo-poo the side effects of statins and say they're non-existent. Well, I think that's a

00:43:01.300 ridiculous thing to say. There are well-documented side effects of statins, at least three that shouldn't

00:43:06.940 be ignored. One is muscle aches. The two is elevations of transaminases or liver function

00:43:11.580 tests. And the third is insulin resistance. All of these are relatively small, but they're not

00:43:18.160 zero. Two of the three are objectively measurable. Why would we ignore that? So I really like when you

00:43:26.780 have objectively measurable side effects. So I would say that if a young person is in a situation

00:43:33.340 where perhaps they can't afford bempendoic acid, Nexlizet, PCSK9 inhibitors, because to be clear,

00:43:39.080 those drugs are expensive at this time and statins are not, yeah, your alternative might be,

00:43:44.160 I'm going to be on a statin, at least go through the trouble of trying to find the right one that

00:43:50.320 produces the fewest side effects. Again, we think that probably Pitavastatin or Livolo,

00:43:57.520 Resuvastatin or Crestor, probably the best places to go, but it's also so highly individualized that

00:44:05.280 I think you just have to try a couple until you find the ones that are doing the best

00:44:08.400 without any collateral damage. You've talked about PCSK9s before, but

00:44:13.380 do you think we're any closer to those being more widely available? And by widely available,

00:44:18.680 just meaning at a potential lower cost to individuals? I think so, because we now have,

00:44:24.640 through a different mechanism, you have a shot that can be administered once every six months.

00:44:30.040 So I think that the twice monthly shot that I take for a PCSK9 inhibitor, which has already come

00:44:35.700 down in price by more than 50% since that drug came out eight years ago, I think there will just

00:44:40.820 be continued price pressure on these drugs as more and more other drugs become available.

00:44:45.360 Speaking of drugs, you mentioned before you think for the future of LP little a,

00:44:51.240 that there's a drug in the pipeline that you're pretty optimistic about being available for people

00:44:57.440 who have a high LP little a, which could be anywhere from eight to 12, up to 20% of people.

00:45:02.480 And we've had podcasts on that before. And so just with the amount of people that have a high LP little

00:45:07.220 a, often they'll reach out because up until now, there's not really a drug that can lower that.

00:45:13.420 So do you just maybe want to talk a little bit more about

00:45:15.540 what's on the future for LP little a medications?

00:45:20.220 Truthfully, I haven't been following anything for the last few months. So I don't have anything

00:45:23.760 new to say on this since I probably last spoke about it, but there is a drug being made by a

00:45:28.960 company, I think in San Diego that is an antisense oligonucleotide. So the drug disrupts the process of

00:45:35.920 DNA making RNA to make APO little a. It interrupts the synthesis of the protein that turns an LDL into

00:45:44.880 an LP little a. The drug worked very well in phase two. So in phase two studies, which don't have

00:45:52.380 clinical hard outcomes, the outcome is just, is the biomarker improving? There was a complete

00:45:58.860 obliteration of LP little a and there were no side effects over the short haul. So what matters now

00:46:06.800 is the phase three trial, which is ongoing. And that's testing the more important question,

00:46:12.400 which is does eliminating LP little a via this mechanism reduce clinical events? Does it reduce

00:46:19.720 major adverse cardiac events? So the answer to that question will determine whether or not this drug

00:46:25.800 is approved and therefore becomes available. But I will say this, it is unlikely for me to imagine

00:46:31.740 that that drug will be approved to treat patients with primary prevention because the manner in which

00:46:38.520 it's being tested understandably is for secondary prevention. This is very common in drug development

00:46:44.420 where you first test the drug, the clinical indication is in the highest risk patient. So you get

00:46:49.200 the answer relatively quickly. So this is a trial that is looking at people who have already had major

00:46:54.760 adverse cardiac events. And it's basically seeing, can we prevent subsequent events? And if the answer

00:46:59.380 is yes, I believe the drug gets approved, it gets approved for that use case, it would still be able to

00:47:05.700 be used by anybody for primary prevention, but it's not likely that an insurance company would pay for

00:47:10.300 that yet. Very interesting. What's a traditional timeline for drug development to go from that first use

00:47:18.920 case, which is the most urgent to that primary prevention. Is that usually years over a decade?

00:47:27.540 The rule of thumb is one decade and $1 billion for a drug to go from IND to FDA approval. And again,

00:47:34.060 once a drug is approved by the FDA, anything can be done with it. It can be used off label.

00:47:38.080 In the case of statins, they were very quickly employed for primary prevention, probably even before

00:47:44.160 primary prevention trials were published because the drugs weren't that expensive. The only reason I think

00:47:48.520 this is an issue here is I do not expect this drug to be cheap. Got it. Anything else you want to say

00:47:55.300 on the drug supplement category before we move on? Only that I can't believe we wasted how many ever

00:48:01.040 minutes we wasted talking about that. As a reward, you get to talk about nutrition. We go from one

00:48:07.400 positive to another. The first question is what set of words trigger you more when you are asked

00:48:14.980 which diet is best, which diet is best, or what is good cholesterol and bad cholesterol?

00:48:23.760 I don't know. Those are pretty upsetting questions.

00:48:30.320 Let's start with the second, considering we just hit ASCVD. You made a YouTube video about this,

00:48:36.260 but I do think it's an important subject because not only is there a misunderstanding of this

00:48:40.800 with patients, but also the amount of doctors out there who I think still use good, bad cholesterol.

00:48:47.580 Do you just want to give a rundown why there is no such thing as good and bad cholesterol?

00:48:53.820 The term originates from the differentiation between low-density lipoprotein, LDL, and high-density

00:49:01.620 lipoprotein, HDL. Let's start with where there's a grain of truth here. LDL, or low-density lipoprotein,

00:49:08.580 which is not cholesterol. LDL is the carrier molecule. It's the low-density lipoprotein. It's

00:49:14.660 the boat or the submarine that carries cholesterol. LDLs are bad, and HDLs, high-density lipoproteins,

00:49:23.620 are good. But HDL and LDL are not laboratory measurements. There's such a thing as an LDL or an

00:49:29.800 HDL that you can check at a lab. You can measure the content of cholesterol within the LDL. That's

00:49:35.880 called LDL-C. Similarly, you can measure the content of cholesterol within the HDL. That's

00:49:41.440 called HDL-C. When you have a basic lipid panel and it says your HDL is 50, well, if you read the

00:49:49.160 fine print, what it's actually saying is your HDL cholesterol concentration is 50 milligrams per

00:49:54.020 deciliter. Don't say that your LDL is 120. Say that your LDL cholesterol is 120 milligrams per

00:50:01.580 deciliter. It's very important, I think, to be accurate in our nomenclature.

00:50:04.160 So the reason that saying there's good cholesterol and bad cholesterol is nonsensical is because

00:50:08.660 cholesterol is cholesterol is cholesterol. The same molecule of cholesterol inside the HDL

00:50:13.540 is present inside the LDL. What's bad about the LDL is that the LDL traffics that cholesterol into

00:50:21.720 the artery wall where it will get retained and oxidized and lead to the process of atherosclerosis,

00:50:29.300 whereas the HDL will not do that. That's the fundamental difference. We should really never

00:50:35.400 say good cholesterol and bad cholesterol because it's highly inaccurate and it only reflects a lack

00:50:40.900 of understanding of what one is talking about, which is why it certainly would be a red flag if a doctor

00:50:47.040 ever said that. And then moving to the nutrition side, do you maybe want to take a minute to talk about

00:50:53.760 why nutrition research is so flawed and so hard to do? And then how, because that's true,

00:51:01.780 that kind of affects everything you look at within nutritional epidemiology and trying to understand

00:51:08.920 that question of which diet is quote unquote best?

00:51:12.460 Well, I mean, we could spend an hour on that question, which I don't have the appetite for.

00:51:18.980 I think it comes down to the complexity of the organism at question, which is us,

00:51:23.220 and the complexity of the intervention, which is eating. So it's really the worst of both worlds.

00:51:29.840 We can study something as complicated as nutrition in a simple organism that can be put in a cage

00:51:35.320 where you can control everything and where lifespan is short enough that you can actually measure

00:51:41.020 how inputs affect outputs on a reasonable timescale. But to be clear, even studying the effects of

00:51:47.300 nutrition in a confined environment using more complicated organisms, such as rhesus monkeys,

00:51:53.420 as was the case in the NIA Wisconsin experiments from the 1980s, which again began in the late 80s,

00:52:00.700 I believe, that's an experiment that could never be replicated. I mean, it took north of 20 years to do

00:52:06.340 an experiment in rhesus monkeys where you could still have perfect control over what they ate.

00:52:11.020 And it's not entirely clear what the answer was. That was an experiment that sought to test the

00:52:15.220 question, does caloric restriction extend life? And the answer turned out to be, it depends if

00:52:19.620 your monkey lives in Wisconsin or Bethesda, Maryland. Of course, I'm being tongue-in-cheek.

00:52:24.420 I think that study did answer the question if you knew how to read the study. I won't get into that

00:52:28.820 because I think I have a whole chapter devoted to that in the book. That's basically the long and

00:52:32.520 short of why it's so difficult to study. So when you study it in humans, you can do controlled

00:52:38.160 experiments in a research setting, but by definition, they can't tell you anything about

00:52:43.260 health in the long-term sense because it would be almost impossible to confine humans for more

00:52:49.100 than a month or so and control everything they ate. So one can do those types of experiments to

00:52:54.520 understand very precise mechanisms of action, but those rarely translate to a clear understanding

00:53:00.400 of health. If you want to understand what happens over the course of a year, three years, five years,

00:53:06.220 10 years, by definition, you have to do that outside of a hospital and you have to do it with

00:53:12.000 patients being able to eat what they want. There are some historical exceptions to this rule. So for

00:53:17.260 example, the Minnesota coronary study was a seven-year study that was, well, I shouldn't say that. I think

00:53:23.500 the actual intervention was probably closer to three or four years. I could be wrong on that,

00:53:27.240 but it was done on patients in a nursing home. And there you had the interesting situation where you

00:53:32.340 had patients who were relatively old, therefore at high risk for ASCVD, but the investigators had

00:53:38.800 complete control over what those patients ate because every meal was being provided to them.

00:53:43.300 That experiment was rather interesting in that it did not yield what the hypothesis suggested.

00:53:48.480 I think there's lots that could be learned from that potentially, but net-net, this is why nutrition

00:53:53.700 in humans tends to rely heavily on epidemiology, where you are looking for patterns without doing an

00:54:01.140 experiment, without randomization. So with your patients then, are you still continuing to try and

00:54:07.500 manage their nutrition, manage their diet, not to you put everyone on the same diet, but more so

00:54:14.920 what is that patient doing and how do you get the best metabolic health for that patient?

00:54:21.340 Yeah, I mean, we think that the most important parameter for determining metabolic health is energy

00:54:26.780 balance. So even the quote-unquote best diet, if it's in excess of energy balance, will produce

00:54:33.960 poor metabolic health. So regardless of what you think the best diet is, if you think it's a keto diet

00:54:41.020 or a paleo diet or a low-carb diet or a Mediterranean diet or a vegan diet, take any version of those and

00:54:47.900 consume them to excess to the point where you are no longer in energy balance and you are accumulating

00:54:52.860 adipose tissue that leaks out of the subcutaneous space and gets into the liver, gets into the

00:54:58.500 viscera, you're going to be unhealthy. So I always think people are majoring in the minor and minoring

00:55:04.160 in the major on nutrition when they start to fight in dietary tribes on this stuff. There are some

00:55:09.380 general principles. Look, I do still think that clinically, in my experience, patients with profound

00:55:15.460 insulin resistance tend to respond better to carbohydrate restriction as the best tool to

00:55:21.680 reduce total intake. You have to create a caloric deficit in those patients. And in my experience,

00:55:27.460 they respond better to carbohydrate restriction than they do straight caloric restriction or fat

00:55:33.560 restriction. Ultimately, it matters most that you can find something that is manageable and sustainable

00:55:39.480 over the long haul. None of this matters if you can adhere to the perfect diet for three months and

00:55:45.320 then you can't. It's better to have a seven out of 10 diet in terms of quality and perfection that

00:55:53.520 you can sustain indefinitely than a 10 out of 10 diet that you can only sustain for three or six

00:55:58.080 months. Some other questions we see come through are questions where people are kind of confused on

00:56:03.680 why should we not just look to populations with longer lifespan and attribute their longevity to their

00:56:11.640 diet. So there's different populations around the world who will traditionally live longer.

00:56:17.500 And so do you associate their longevity with their diet? Is that a mistake for people to do?

00:56:23.640 It's a complicated question because there are probably too many factors that factor into

00:56:28.960 why these populations live a long time. So if you look at, for example, the Okinawa,

00:56:34.660 where everybody loves to talk about the Okinawa in Japan, unquestionably a very long lived people.

00:56:39.660 Although I've read recently, not as long lived as the current generation of Okinawan adopt a more

00:56:47.120 Western lifestyle, inclusive of diet, by the way, a lot of those things seem to go away. So it suggests

00:56:54.180 that it might not just be the diet that is responsible for the benefits that these cultures

00:57:00.580 are bestowed with. So what are some of the other things that could factor into that? Well,

00:57:04.620 we could certainly look at activity level, exercise level, sleep, stress, social connections,

00:57:13.260 lack of other toxic elements in the environment. I think the same exercise is true when you look

00:57:19.660 across all of these populations. The other reason that I think it's very difficult to say there's any

00:57:25.380 one perfect diet is when you look at these different populations and pockets over the past hundred

00:57:33.720 years that have popped up and have been studied who seem to outlive others, even in relative proximity

00:57:41.540 to them. Their diets are actually quite diverse. So what does that tell us, right? So if you have

00:57:48.440 people in Japan and people in Switzerland and people in this part of Africa and people in this part of

00:57:55.040 the Arctic or whatever, where you see reasonable pockets of longevity, but their diets are relatively

00:58:01.260 diverse. It might be interesting to look at what's missing from all of the diets or what do they have

00:58:06.760 in common in their absence or what do they have in common in their presence. But to me, at least it

00:58:11.520 suggests that there's probably a pretty robust nature within the human to manage a variety of different

00:58:21.380 dietary conditions. Again, it comes down to provided energy balance is met. And I think provided that a

00:58:28.280 person stays metabolically healthy. So they're active, they're sleeping well, cortisol levels are not

00:58:33.460 through the roof. All of this is to say, I think our diets are problematic in this country, but I don't

00:58:39.900 think that changing the way people eat alone will turn us into quote unquote, a blue zone.

00:58:47.360 You hinted at this earlier question we get asked a lot, which is, are you still doing your longer

00:58:53.140 fast? And if not, why is that? I'm not. And I think there were several reasons I'm not, but truthfully,

00:59:01.220 perhaps one of the most logistically relevant ones is just, I don't travel anymore. I used to only do my

00:59:07.800 long fasts when I was traveling, when I was away from home. And it was just so much easier to be fasting

00:59:13.980 when I was in New York than being at the time in San Diego. But now I never travel. So it would mean

00:59:21.820 that if I wanted to do long fasts, I'd be doing them at home and I just don't feel like doing it.

00:59:27.600 And I don't have a better answer than that. I think it also speaks to the fact that I don't

00:59:32.120 have a clear sense of what the benefit is. This is one of those things where I'm going to reserve

00:59:36.000 the right to completely change my mind. If I had some biomarker that could convince me that a seven

00:59:40.600 day fast, even once a year, had a meaningful rewrite on some negative processes in my body, I mean,

00:59:47.980 I would happily make that sacrifice again. But in the absence of knowing that the cost is a bit

00:59:53.100 high right now. Another thing on the nutrition side that you talk about a lot is the importance

00:59:58.320 of protein. We just did a premium email that kind of looked at the pros and cons of protein, because

01:00:04.200 when you look at protein and aging, it does seem like it's a bit controversial in sense of what people

01:00:10.680 will recommend. And so the question that came through and comes through often is, if someone's

01:00:17.400 under 50, so let's say you're 30 or 40, do you think it's important that they err on the side of

01:00:24.100 caution and eat less protein based on the research? Or do you still think no matter what age you are,

01:00:30.660 protein is so important and that everyone should be getting as much as possible of it?

01:00:35.480 I think it depends on how much muscle mass that person has. So if you have an individual

01:00:41.100 who's overnourished and adequately muscled, so they're overweight, but they actually have a

01:00:49.760 sufficient amount of muscle mass and they need to go into a caloric deficit, we would certainly tolerate

01:00:55.380 also a little bit of a protein deficit in that individual. Not because I think it's necessary,

01:01:00.860 but because I think it's easier to hit caloric targets if you are able to relax your protein

01:01:07.120 targets. In other words, if you say you need to be in a caloric deficit and hold one gram of protein

01:01:13.160 per pound of body weight, that becomes really challenging. If you say, look, you could be at

01:01:17.440 0.6 to 0.7 grams of protein per pound of body weight and create a caloric deficit is much easier.

01:01:24.080 Conversely, if a person is overnourished and under muscled, I think we do have to toe that fine line

01:01:29.540 of keeping protein high because that person needs to be putting on muscle as they're losing fat.

01:01:34.980 The truth of it is, I don't find the data for people below 50 having an increase in mortality

01:01:40.580 with high protein being at all convincing. I think that is easily attributed to caloric excess as

01:01:47.060 opposed to protein excess. And I think that there are enough other confounders there that it's really

01:01:52.160 a proxy for poor health than it is a proxy for high protein. Furthermore, the absolute mortality

01:01:57.940 in people below 50 is so low in terms of absolute amounts that even a slight increase in the relative

01:02:05.920 amount is trivial. Finally, it's very important when people are still able to put on muscle that

01:02:12.260 they put on as much as possible because once you're in the over 50 category, you're kind of

01:02:18.180 clawing on for dear life and trying to keep as much of that muscle as possible. So I don't really want

01:02:23.300 people entering middle age with a muscle deficit. This kind of goes back to our original question.

01:02:28.280 Like even if someone comes up with the solution for cancer and Alzheimer's disease and all of these

01:02:33.780 other things, you still have to ward against frailty. You still have to make sure that you enter that

01:02:39.340 marginal decade physically robust. And most people don't come close to it. They're really, really

01:02:45.040 under muscled late in life. Another question we get asked a lot is how do you eat so much protein in a

01:02:51.960 day? As we're kind of going through Peter protocols, why don't you just run us through

01:02:57.040 your protein per day and what that looks like? Again, I have the luxury of being at home. So

01:03:02.580 I have more control over what I eat than if I was back on the road, but I get a lot of it through

01:03:07.660 venison. So Maui Nui, again, disclosure, I'm an investor in that company. They make a really,

01:03:13.380 really good venison jerky stick. And I love it because it has no garbage in it. It's literally just got

01:03:19.740 some natural flavors in it. I absolutely love the taste of it. So that makes life easy. And each

01:03:25.380 stick, I eat the peppered ones, has like 9.9 grams of protein in it. It's funny, the USDA makes you,

01:03:32.520 or I don't know if it's the USDA or whichever governing body determines food labeling, you have

01:03:37.540 to round down. So it says 9 grams of protein on the stick, but it's actually 9.9 grams is what it

01:03:43.500 measures. So I actually think of each stick as having 10 grams of protein. So I will easily

01:03:49.200 throw down five to 10 of those sticks a day. And that would represent one versus two high protein

01:03:55.960 snacks. And then the rest of it, I'm kind of getting in my food, basically. Lately, I haven't

01:04:02.300 really been doing much on the protein shake front because the jerky sticks are just quicker and easier

01:04:07.820 for me than making a shake. But I would also use a high quality whey protein shake if necessary.

01:04:13.940 So it's not that hard for me to kind of hit my goals throughout the course of a day. And by the

01:04:18.700 way, what am I targeting? Somewhere between 150 and 180 grams of protein per day. And how often is

01:04:25.440 that spread out between? Typically like four hits. Yeah. I've been in plenty of meetings with you where

01:04:31.640 you'll walk in with just a handful of jerky sticks, drop them on the table. You'll be like anyone else

01:04:37.560 want one. And then within 15 minutes, they're all gone and all the wrappers are right in front of

01:04:42.180 you. So I can attest that I've seen you do that protocol for sure. Anything else on the nutrition

01:04:48.700 front you want to talk about before we move on? No. All right. Next section, wearables. What is your

01:04:57.980 current favorite wearable or just a device that tracks things for you? So maybe it doesn't have to

01:05:03.760 be something that is like on your body at all times, but just what's your favorite device for

01:05:08.900 tracking? And it can be tracking anything. I've been using something called Morpheus lately. It's

01:05:14.820 got two heart rate monitors. It's got a chest strap and a wrist strap, not a wrist, a forearm strap.

01:05:19.560 It's got an app that in the morning you lay down and put the heart rate monitor on and you answer

01:05:27.540 four questions. How long did you sleep last night? So I checked my eight sleep for how long I slept.

01:05:32.700 And then how well did you sleep? So I look at my eight sleep score and get a sense of the quality

01:05:38.100 of my sleep. And then I enter that. And then how do I feel and how sore am I? So it asks these four

01:05:45.320 questions and then I do a two minute lay down with the heart rate monitor on and it measures my heart

01:05:51.420 rate and my respiratory rate and my heart rate variability. And then it spits out a readiness score

01:06:00.840 and it provides training zones via heart rate for the day. So for the past six months, I've been doing

01:06:08.300 an experiment where every time I do a zone two workout, I'm using the heart rate that it predicts.

01:06:16.320 I'm riding to my RPE and then I compare the lactate at the end of that ride to the predicted

01:06:23.360 heart rate from Morpheus to the RPE heart rate. And I will say that it tracks pretty darn well,

01:06:30.820 better than I would have expected. And the reason I'm doing this is to see if this could be a good

01:06:36.200 tool for our patients to use who might not be as clued in to their own RPE and who clearly don't want

01:06:44.020 to check their lactate levels. And are you using Morpheus for anything? Do you use any of that data

01:06:50.100 for anything outside of zone two? Are you using it for how hard you'll push that day lifting and

01:06:55.620 anything like that? I don't. Certainly that's how they would suggest you use it. I don't wear it

01:07:00.940 outside of my zone two or VO2 max training. So I don't wear it when I'm in the weight room. I don't

01:07:05.440 wear it rucking in large part because I hate wearing heart rate monitors in general. I don't find them

01:07:10.200 comfortable. I can sort of tolerate it when I'm on a bike, but I don't want to be rucking with one.

01:07:13.660 I don't want to be lifting with one. It's probably the case that it would be an even better predictor

01:07:19.580 of my training if it could see me across the day. If it could see me train in every workout,

01:07:26.160 it would probably be an even more effective tool because it would understand where I am in terms

01:07:30.980 of overload. Another wearable we get asked a lot, you've talked a lot about this, and I believe you

01:07:35.920 still use it with a lot of patients, is CGMs. Is that something you're still using a lot with your

01:07:41.560 patients? We do. Yeah. We use CGM a lot. It's a great tool. When we have questions, it provides answers.

01:07:48.920 We could sit here and look at a person's OGTT. In some cases, it's just a slam dunk. This person

01:07:55.780 isn't super metabolically dialed in. In other cases, it's a complete slam dunk. This person

01:08:01.360 has type 2 diabetes by OGTT criteria, even if not by A1C criteria. But there are a lot of people in

01:08:07.880 the middle. This is a great way that we can glean more information and really dial in our treatment

01:08:15.820 for them. And so there was some controversy way back when on if CGMs were still valuable,

01:08:24.040 still useful for people who are non-diabetics. Have you changed your opinion on that at all?

01:08:29.860 Not one bit. Do you maybe just kind of want to walk through people what you look for with CGMs and

01:08:36.960 ultimately what people, if someone's wearing one, because it seems like it is more widely available

01:08:41.860 for non-diabetics now. And so you see a lot more of them around. So if someone gets one,

01:08:47.380 what are some of the things you like to see within patients? What are some of the things you look at?

01:08:52.940 How do you use it?

01:08:54.540 I mean, we still look for the same things. I think average blood glucose is still the most

01:08:58.140 important metric we care about because that's the one for which we have the most data. In other words,

01:09:02.780 we know all-cause mortality data as it relates to hemoglobin A1c. Hemoglobin A1c is a measurement

01:09:10.240 that's used to impute average blood glucose. So this is a very, very close proxy. When we can see

01:09:16.540 average blood glucose on CGM, even though that's not the same as measuring A1c, it's very difficult

01:09:21.880 to argue that knowing your average blood glucose on CGM and knowing your A1c aren't highly comparable,

01:09:28.200 and therefore by proxy, the lower your average blood glucose on CGM, the lower your all-cause

01:09:34.240 mortality. Because it is abundantly clear that the lower your hemoglobin A1c, even outside of the

01:09:40.120 diabetic range, the lower your all-cause mortality. So first and foremost, that's the metric we care

01:09:44.700 about. The other metrics we look at, of course, are what's the standard deviation? So all things equal,

01:09:50.260 do you have less variability in your glucose than more? And then finally, and the least important,

01:09:56.040 I think, is how big are the spikes you're seeing. Now, in truth, that becomes less important if the

01:10:03.100 first two are reasonable. If a person's average blood glucose is 98 milligrams per deciliter with

01:10:08.140 a standard deviation of 16 milligrams per deciliter, it doesn't really matter what kind of spikes they

01:10:13.260 have because they're clearly not going to be too many unless they're using insulin. You could obviously

01:10:19.520 arrive at those numbers the wrong way. So I would say that fixating on average blood glucose and standard

01:10:25.180 deviation are probably the most important thing. From when you would wear one, do you recall what

01:10:30.380 caused the biggest spike you ever saw? No, I don't recall. A buddy of mine took me to this vegan

01:10:36.840 restaurant in New York once. I think it was called like Candle 79 or something. It was really close to

01:10:42.560 my apartment. And it was great. It was amazing food. But obviously, by definition, like it's just

01:10:48.640 basically all carbs. And I remember the dessert was so incredible. And I remember looking at my CGM

01:10:58.200 after and it was like 180. And I feel like that's about the highest I'd ever seen.

01:11:02.200 Funny. Do you think we're any closer to continuous blood pressure monitors?

01:11:10.300 Absolutely.

01:11:11.340 You do?

01:11:12.200 Oh, yeah.

01:11:12.620 How far out do you think that is? Because I know in the past with Ethan Weiss, the AMM blood pressure,

01:11:18.360 you've talked about how important that is as a device.

01:11:21.800 I think we have it. So I think the Actia device works. At least it works as well as an automated

01:11:28.540 cuff works. So this is a device that is not yet FDA approved, but it is approved by the similar

01:11:36.260 governing bodies in Europe. So this is a device that's already on the market in Europe.

01:11:39.800 It's a bracelet that you wear that optically measures a signal in your wrist. And you calibrate

01:11:46.920 it against an automated cuff. And every two hours, it gives you your average blood pressure. So over

01:11:54.180 the course of a day, you'll get 12 blood pressure readings. I would say even though automated cuffs

01:11:59.360 in general aren't nearly as good as manual cuffs, for an automated cuff, I don't see any difference

01:12:05.640 really between this and pick your favorite automated cuff. So I really hope that this device

01:12:11.640 gets approved in the U.S. because we'll certainly have every one of our patients wearing this. And

01:12:16.460 it would do away with ambulatory blood pressure cuffs, which are cumbersome and difficult to use

01:12:22.460 and low compliance and artificial.

01:12:24.940 Interesting. So any listener viewer in Europe would have access to this.

01:12:31.320 That's right.

01:12:32.060 And then what do you think the rough timeframe for people in the U.S.? Is it years, a decade? How does

01:12:40.200 that process typically work?

01:12:42.060 It's entirely dependent on the FDA. It's possible it doesn't get approved at all if the FDA is

01:12:49.060 difficult to work with on this. Unfortunately, I hope that's not the case.

01:12:53.600 So if anyone listening and watching works for the FDA, something to internally push on then.

01:13:00.440 Yep.

01:13:00.920 Any other wearables that you're excited about, whether they're close to being here or even

01:13:07.320 in the longterm, like 10 plus years?

01:13:10.340 I would always welcome continuous lactate monitoring during exercise. That would really,

01:13:15.660 really make zone two training enjoyable for me.

01:13:18.620 Just as opposed to having to do the finger pricks all the time or just knowing where it's at?

01:13:24.660 To me, it's the most accurate way to really understand what's happening. I mean,

01:13:28.260 even heart rate and RPE are just approximations for what you're really interested in.

01:13:32.840 So I think, yeah, just being able to monitor lactate levels while you're exercising,

01:13:36.900 especially doing cardio training. I'd also love to be able to do my VO2 max workouts with a

01:13:42.240 lactate meter, continuous lactate meter. So I could actually watch lactate rise and clearance on each

01:13:48.360 subsequent set. As I'm fatiguing, am I really just breaking down metabolically as much as anything

01:13:53.880 else?

01:13:55.040 So Peter, I think that was the majority of the questions we wanted to get through.

01:14:00.620 As we kind of said at the outset, those are questions that come through often. So we compiled

01:14:06.600 them here, but any closing words you want to tell people?

01:14:11.140 No. What episode number are we at roughly?

01:14:14.740 Well, at the time of this recording, 267. So this will be in the 270s, creeping up on 300,

01:14:25.540 but also at the time of this recording hit five years as a last month, which is crazy because

01:14:33.500 that's what was fun to have David Savantini and Matt Caberlin back on is because they were not only

01:14:39.240 the first 10 episodes, but if I remember correctly, I think that was you and Bob interviewing them and

01:14:45.380 recording it for the book that we then turned into a podcast, which one shows that we didn't even think

01:14:52.460 about the podcast at that time. And two, it shows how freaking long you wrote that book for.

01:14:57.160 That's right. I remember those interviews. I went up to Boston with Bob in the summer of 2017

01:15:02.520 to interview David and then Matt came to New York and I interviewed him a month later and that's like

01:15:12.300 a year before the podcast came out. So yes, that was literally just done for the book. Pretty funny.

01:15:19.160 Yeah. It's kind of crazy to see how far things came along, not only with the podcast, but also now

01:15:25.020 seeing the book out and the reception from that, which is great because we've joked about it before,

01:15:30.040 but I think we can both seriously say there was a lot of periods of time where we didn't think that

01:15:34.280 book was ever going to get released. Yeah. Right up until a couple of months before.

01:15:38.480 Yeah. Yeah. All the way up until 2023. So awesome. Well, hopefully people enjoyed this kind of a

01:15:45.040 little different of a style, but until next time, Peter, have a good one. You too, Nick. Thanks, man.

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The Peter Attia Drive - October 23, 2023

#276 ‒ Special episode： Peter answers questions on longevity, supplements, protein, fasting, apoB, statins, and more

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