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A | Welcome to the Huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Doctor Peter Attia, his second time on the podcast. Doctor Peter Attia is a medical doctor... |
B | Thanks man. Good to be back and sounding better this time. |
A | Looking forward to talking about a number of important topics with you that you cover in your book. Maybe we could start off by trying to set the frame for what people should be thinking about in terms of vitality and especially longevity. |
B | So, I mean, I think you have to be mindful of how you define these terms, and I'm not going to suggest that the way I define them is the only way or necessarily the best way, but I think from a clinical perspective, it's the way that makes the most sense to me, having thought about this for the better part of a decade.... |
A | So, with all of that in mind, what are the major exit points for people along the lifespan route? Let's just start with the binary one. Dead or alive. Most everyone who's healthy would like to be alive rather than dead. So what are the typical ways that people exit from alive to dead? And how can people stay on the fre... |
B | So this is, again, a great analysis. We internally, in our practice, call this the death bar analysis. And it's a surprisingly trivial analysis that I'm just surprised the death bars aren't plastered front and center on every doctor's office. So if you simply just look at actuarial data, which are readily available thr... |
A | How does the number change when you include cerebrovascular disease? |
B | Yeah, it adds. It adds a bit to it. Cerebrovascular disease has. There's largely speaking, you can die sort of through embolic events, which are the majority of them. |
A | Can you explain for people what embolic events are? |
B | Yeah. So, taking a step back, what does the brain need more than anything? It needs blood flow. Anything that interrupts blood flow to the brain that results in ischemia is devastating, and it's devastating in a more readily apparent fashion than virtually any other organ. So one way that that can happen is if a clot o... |
A | I don't want to take us too far off on a tangent, but as long as we're here talking about bleeds versus clots, what are some of the major risks for bleeds? I mean, I know some people out there have genetic predispositions for being bleeders, as they're sometimes called, or clotters. So things like factor five leiden mu... |
B | Well, I mean, there might be sort of two different things going on in that question, but I think if your question is, when we look at the subset of people who are at highest risk for hemorrhagic strokes, the far more germane question is not underlying coagulopathy. The far more germane question really comes down to blo... |
A | Okay, so I'll just briefly interrupt and ask. Since sometimes your recommendations deviate from the. The standards that one would find online or in the typical doctor's office, at what point do you get concerned? |
B | Well, I actually find myself quite in line with the most recent available data on blood pressure, and this has been obviously a topic that's of high concern to any doctor who's taking care of patients, who even pays a fraction of attention to the available literature, which is that basically, with each subsequent blood... |
A | That cuff they put on and that squeeze bulb. |
B | Yeah. If you look at the rigor with which you need to measure a person's blood pressure, the right way to do it is the person has to be sitting like this for five minutes doing nothing. |
A | Okay, folks, so when you go to the doctors now, you don't let them. |
B | Don't let them take your blood pressure. |
A | Out of the gate sitting for five minutes, and that doesn't include in the waiting room, because if you get up and walk over. Right, okay, so make them stand there. |
B | Right. So you. You want to be sitting there like this. A manual cuff is better than an automated cuff, but not enough people use manual blood pressure. So a manual blood pressure means they put a cuff on you and they actually put a stethoscope on the brachial artery, and they're using the human ear to listen, which, be... |
A | Maybe this is a silly question, but can people check their own blood pressure? |
B | Meaning manually? |
A | Yeah. Just, could I get a coffee and a bulb and learn how to do it? |
B | Yeah, I think so. I mean, I can do it, but honestly, I usually have my wife do it. She's a nurse. But it's not rocket science to check blood pressure. I guarantee you there's a great video on YouTube that explains the physiology of it. And if you're willing to splurge on a good enough stethoscope and cuff, like, the cu... |
A | I mean, given the importance of blood pressure and this arteriosclerosis being at the top of the list of, uh, risks for, um, dying, um, it seems to me it might be worth the expense. What. What's a typical range of costs for. For the quality? |
B | It's not inordinate. I feel like my blood pressure cuff is $40 and the stethoscope is a couple hundred bucks if you're getting a good one and a good automated cuff. I have no affiliation with any of these companies. I use two automated cuffs. One's called withings, and the other one's made by a company called Omron. Om... |
A | So how often? Let's say someone buys this? Because I think for $240. I mean, I realize that's prohibitive for some people, but given the cost of some of the other things that are discussed on this and many other podcasts. |
B | First of all, I would just have people start with an automated cuff to begin with and just start with there. We generally have people do it for two weeks. We give our patients a little spreadsheet that automatically calculates averages and stuff like that, tells them what to record and where, and we just say, look, for... |
A | Will a day ever come when a watch or a wristband can do this really well? |
B | So I hope so. And I'm investigating it. I'm actually going to be trying one out in a couple of weeks with a company that I tried two years ago. Two years ago, when I tried it, I was not impressed, so I kind of punted on it. The company, which I guess I'll not share the name of the company just yet, but they claim that ... |
A | So I don't want to stroke, I don't want to bleed in the brain. I don't want to clot. As long as we're at this number one on the list, arterial sclerosis being the number one killer, what are the major ways to prevent it? |
B | Yeah, so there's three big ones that stand out top and center, and then there's kind of a fourth one that I think is the foundational piece. So the three big ones we've talked about, one blood pressure. So if your blood pressure is 120 over 80 or better, that's important. The second is not smoking. So it turns out that... |
A | I want to talk about APOB in depth, but as long as don't smoke is the second recommendation on the list, can we better define smoking and what's being smoked? So assume nicotine. What about cannabis? And what about vaping of nicotine in cannabis because vaping has become so much more common? |
B | Yeah, it's a great question, and it's sadly something we don't have a great answer for. So I can certainly tell you that there's no reason to believe that smoking cannabis is somehow better than smoking cigarettes, but the dose seems to be significantly lower. In other words, let's consider a person who smokes a pack a... |
A | Probably not. |
B | Yeah. So while on a joint to cigarette basis, they're probably equivalent in terms of harm, I don't know. Let's say a person smokes a joint a day. That would be like smoking a cigarette a day. That's a 20th of a pack. Again, I don't want to say that there's no downside to that, but it's probably significantly less. So ... |
A | For those listening, Peter spaced his hands far apart for gum and smoking and put vaping about a third of the way from gum toward smoking. In other words, vaping isn't good for you, but it's not as bad as smoking. |
B | That would be my. That would be my. I mean, do you have a. You've probably looked into this as well. |
A | We did an episode on Nicotine. I did an episode on Cannabis. And, you know, the discussion around cannabis gets a little contentious for reasons that aren't important. It's kind of funny, people, the moment someone starts to confront cannabis as a potential health harm, people say it's not as nearly as bad as alcohol, ... |
B | Yeah. I think sometimes people would benefit to imagine what the surface area of the lung is. If you took the alveolar air sacs of the lungs and spread them out, you would easily cover a tennis court. |
A | Remarkable. |
B | So just think about anytime you inhale something you are exposing, your body is so adept at absorbing it. I mean, we have this unbelievable system for gas exchange that was designed for gas exchange, and anytime you're putting something else in that wake, you're doing a really good job of getting it into your body. So ... |
A | It makes sense during the fires, which seemed to follow me because when I was in northern California, there were a bunch of fires and we were constantly looking. Wake up in the morning, everything was covered with ash. My dog was having trouble breathing. I was having trouble breathing. Everyone was suffering. But ther... |
B | Yeah, just, just make it better for people to not die from the direct consequence. |
A | I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podcast. The rea... |
B | Well, it's athero, which is easier because. Yeah. |
A | Atherosclerosis. Oh, there. |
B | Yeah. |
A | I've been making life more complicated for myself. Typical of me. Okay, so blood pressure, keeping it 128, 120 over 80 or better. Don't smoke. Let's just throw in, don't vape. |
B | Sure. |
A | I'm going to just plant my flag on it. Just don't vape. There are other ways to get those things in your system if you really want to get nicotine or cannabis into your system. Apob. What's the story with APOB? |
B | Okay, so to explain this, you have to tolerate a little bit of chemistry. So everybody's heard of cholesterol, and I certainly devote quite a bit of time in the book to explaining this because it is so important. Um, and it's definitely one of those areas where I initially received a lot of pushback from the editor, an... |
A | Cholesterol around the body and these proteins that have lipid in the middle. So let's just take apob, for example, many, many billions of them, floating around in our body, even in the healthiest of people, and they're being shuttled to tissues that need them, like the adrenals, muscle, heart, et cetera. What sets the... |
B | We don't have any evidence of that to date. All of the functions that I described can be done by the HDL. So the high density lipoproteins, the apoas can do all of it. |
A | So ApOb and low density lipoproteins are just. They're just the necessary. |
B | We don't waste. I mean, no, we don't understand why we have them. Andrew, this is the part that's really interesting to me. Most species do not even have apob, and as a result of that, most species are chemically incapable of atherosclerosis. |
A | So if someone could zero out their APOB and their LDL, we assume they would function just fine. |
B | We know they would, because we have certain people who walk around with genetic mutations that render them that way. |
A | Wow. |
B | Furthermore, we also know that there's a bit of a myth out there that cholesterol, the cholesterol you measure in your blood, is essential for brain health, for example. That's an understandable thing, right? You can speak to this very eloquently, the role of cholesterol in the brain. |
A | Yeah, I wrote down when I was a postdoc at Stanford, so I always point out I was born in Stanford, training at Stanford, where he said I'd probably die at Stanford. Hopefully a long time from now, you'll tell me how long, for you. |
B | Well, we're going to do the Charlie Munger thing and make sure that you never go back to Stanford so that, like, you can't die there, there. |
A | Exactly. We cured already. When I was a postdoc, I worked with a guy named Ben Barris, who I know, you know, probably as a different person then for reasons that people can look up Ben's name. Anyway, incredible scientist. But there was someone in his lab that discovered that cholesterol is a critical component of the ... |
B | Yeah. It's not entirely clear why, but here's what we know. When you're born, your serum cholesterol levels are very low. So children, infants and children have very low levels of cholesterol. They would have and I should explain one thing that's important. |
A | They're not myelinated yet, right? I mean, they're. Sorry to interrupt, but myelin, of course, the sheathing around neuronal axons, which accelerates the propagation of nerve signals and which is deficient in things like multiple sclerosis, is essentially fat made up of phospholipid and requires cholesterol for synthes... |
B | So this is what's interesting, right? We would all agree to that. Cholesterol is more important to infants and children than to anybody else. It would be the most important substrate for CN's development. And yet infants and children have virtually unmeasurable levels of cholesterol. It really starts to take off in you... |
A | Fascinating. First time I've understood HDLDL and these lipoproteins in a way that makes sense. So thank you. I'm sure others feel the same way. What APOB level is your red flag cutoff? Right. I actually had my APOB measured recently, and I'm definitely above the high end. |
B | We'll be discussing this over dinner on Saturday night. |
A | And just to tie this back, I hope that's a steak dinner and that should be fine, given the fact that dietary cholesterol has no direct link to APOB and LGBT. |
B | That's true, but dietary saturated fat does. |
A | Okay, so, which is not to say. |
B | We'Re not gonna have a steak. |
A | We will, but not necessarily one of the fattier cuts, although probably will be for me. So what's the high end that you high end flag? At what point do you start saying, ah, we need to do something, and then we'll talk about what people can do? |
B | Yeah. So this is a complicated question because it depends on so many factors. The first factor it depends on is, what is your objective? And I do pose this question directly to a patient. Right. So I say, look, we've got this disease. That's the number one cause of death. Now, you can die with it or you can die from i... |
A | Yes. |
B | So just to be clear, Andrew, you do not think that it's just an association that smokers get more lung cancer? |
A | No, I do not. |
B | In other words, you believe that smoking causes lung cancer, then, yes. Okay. |
A | I mean, there are a number of memoristic steps in between. I mean, if somebody was really wanting to get to drill into the logic, they could say, okay, it's not actually the smoking. It's a. Some disruption of the endothelial cell lining that led to. |
B | But smoking triggers that triggers that. |
A | I assume so. |
B | And I agree with you, by the way. I think the data are very clear. |
A | I'm very relieved to hear that. |
B | Yeah. But I'm going someplace very important here, because if there's one topic that doesn't get enough attention in medicine, it's causality. And causality is an obsession of mine, like, most of the day, on some level, I sit around thinking about causality, and I think the hardest part about studying medicine with res... |
A | By the way, Mendelian randomizations, meaning genetic mutants, humans out there that make very little apob or. |
B | And very much exactly. So we have a whole gradient. |
A | So you can say if you make very little, you aren't going to die as quickly in your life as if you make too much. |
B | That's right. So mendelian randomization is such an elegant tool where you basically let genes do the randomization. And as you said, there is a gradation of LDL concentration, or APOB concentration, that occurs from insanely low to insanely high. And this is a wildly polygenic, polymorphic set of conditions. And we ca... |
A | And if somebody's sitting up in the, say, low 130s, where does that, what kind of flag does that raise for you? I realize it's highly contextual, age, etcetera. |
B | No, no, it's a huge red flag. Again, just because something is causal doesn't mean you're guaranteed to get it. There are smokers who don't get lung cancer, so there's going to be somebody listening to this who says, my grandmother's 95 years old, her cholesterol is sky high, and she's alive and well. And I will say, a... |
A | This issue of causality, I think, now becomes very clear as to why that is so crucial. And I really appreciate the way you spelled that out. So let's say somebody's apob is 8100, let's say 130. Um, for example, what sorts of things can they do to reduce that number? Is this always going to be prescription medication? A... |
B | So, yeah, usually once you want to start getting down into the 30 to 60 range, you're going to require pharmacotherapy. Um, but, you know, usually we want to see how far we can get with nutrition. So fixing insulin resistance in an insulin resistant person will bring this down. Right. So one of the hallmarks of insulin... |
A | Triggs being triglycerides. That's right. But does that mean lowering dietary fat? |
B | No, actually, it's most easily accomplished through carbohydrate restriction. Yeah, carbohydrate triglycerides, in some ways are kind of an integral of carbohydrate consumption. Um, any energy restriction will get it for you. Um, but it's most sensitive to, um, to restriction of, of even. Even under EU caloric conditio... |
A | And where does exercise come, um, play a role, minimal role for improving insulin sensitivity? |
B | No, no, no. I'm sorry. For improving, uh, lipids in general. Yeah. |
A | But it can improve insulin? |
B | Absolutely, yeah. |
A | Especially combinations of resistance training and cardiovascular exercise, correct, yeah. |
B | So once it comes down to pharmacotherapy, you basically have several classes of drugs. So the most obvious and the one that most people are aware of are called statins. So statins work both directly and indirectly on the problem. So directly they work by targeting an enzyme very high in the synthetic pathway of cholest... |
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