Huberman LabImprove Vitality, Emotional & Physical Health & Lifespan | Dr. Peter Attia
EVERY SPOKEN WORD
150 min read · 30,280 words- 0:00 – 3:22
Dr. Peter Attia
- AHAndrew Huberman
(instrumental music) 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 Dr. Peter Attia, his second time on the podcast. Dr. Peter Attia is a medical doctor who did his training at Stanford School of Medicine, Johns Hopkins School of Medicine, and the National Institutes of Health. He is a world expert in all things related to healthspan, vitality, and longevity. In this episode, we focused on many topics, focusing mainly, however, on healthspan and longevity and mental health. Healthspan and longevity, of course, relate to how long one lives, and Dr. Attia goes systematically through the seven major causes of death worldwide, beginning with cardiovascular disease and cerebrovascular disease, also cancer, also accident-related deaths, dementia, deaths of despair, and in every case, explains the three or four major levers that one can employ in order to offset, that is to prevent, those major causes of death. What follows is an incredibly informative and actionable set of tools for anyone, male, female, young or old. He explains the behavioral, nutritional, supplementation-based, and prescription drug based approaches that one can use in order to extend healthspan and longevity. Dr. Attia explains the key tests and markers that we should all pay attention to if our goal is to extend our healthspan and how to do so while maximizing our vitality. This is something that not a lot of people think about when they think about healthspan and longevity, but as Dr. Attia illustrates for us, emotional health has everything to do with our physical health and vice versa, and he shares quite openly about his own experiences in pursuing ways to improve emotional health and thereby healthspan, lifespan, and vitality. Dr. Attia is quite open about his own experiences exploring different practices to improve emotional health as ways not just to improve healthspan, longevity, and vitality, but of course also to derive the most meaning and satisfaction from life. Throughout today's discussion, we also discussed Dr. Attia's newly released book, which is entitled Outlive: The Science and Art of Longevity. This is a phenomenal book. I've read it cover to cover now three times. I have extensive notes written throughout, and the book, of course, focuses on longevity and healthspan and also has an extensive section on emotional health. It gets quite detailed into Dr. Attia's personal experiences with emotional health and tools to improve emotional health that are very actionable for anybody to use. I think the best way for me to summarize my feelings about the book would simply be to read the back jacket quote, which I provided. So I read, quote, "Finally, there is a modern, thorough, clear, and actionable manual for how to maximize our immediate and long-term health. Firmly grounded in data and real-life conditions, this is the most accurate and comprehensive health guide published to date. Outlive is not just informative, it is important." And indeed, Outlive is an important book, as is the discussion that Dr. Attia so graciously provided us in today's episode. Outlive is released on March 28th, 2023, and is available for pre-order prior to that date. You can find a link to where it's sold in the show note captions.
- 3:22 – 7:34
Sponsors: Eight Sleep, LMNT, HVMN, Momentous
- AHAndrew Huberman
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. As I've talked about before on the Huberman Lab Podcast, there is a critical relationship between sleep and body temperature. That is, in order to fall asleep and stay deeply asleep, your body temperature needs to drop by about one to three degrees, and in order to wake up in the morning and feel alert, your body temperature needs to increase by about one to three degrees. The problem with most people's sleeping environment is that even if you make the room cool, the actual environment that you sleep on, that is your mattress and underneath your covers, is hard to regulate in terms of temperature. With Eight Sleep, regulating the temperature of that sleeping environment becomes incredibly easy. In fact, you can change the temperature of that environment across the night, making it a little bit cool at the beginning of the night, even cooler still a few hours into your sleep, which really helps getting into very deep sleep, and then warming it as you approach morning so that you wake up feeling most alert. I've been sleeping on an Eight Sleep mattress cover for over a year now, and it has completely transformed my sleep. If you'd like to try Eight Sleep, you can go to eightsleep.com/huberman to save up to $150 off their Pod 3 cover. Eight Sleep currently ships in the USA, Canada, UK, select countries in the EU, and Australia. Again, that's eightsleep.com/huberman. Today's episode is also brought to us by LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means plenty of salt, magnesium, and potassium, and no sugar. The electrolytes, salt, magnesium, and potassium, are critical for the function of all cells, in particular neurons or nerve cells, and of course, proper hydration is critical for mental functioning and physical performance. To ensure that I stay hydrated, I consume one packet of LMNT in approximately 20 to 30 ounces of water every morning when I first wake up, and I will also consume one LMNT packet in about the same amount of water when I exercise or when I'm doing any kind of mental work, you know, preparing for a podcast, writing grants, working on papers, and so forth. I find that allows me to maintain my focus and physical performance at levels that I just simply can't otherwise. If you'd like to try LMNT, you can go to drinklmnt, that's lmnt.com/huberman, to claim a free LMNT sample pack with your purchase. Again, that's drinklmnt, lmnt.com/huberman.Today's episode is also brought to us by HVMN Ketone IQ. HVMN Ketone IQ is a supplement that increases blood ketones. I want to be clear that I am not following a ketogenic diet. Most people fall into this category, they are not following a ketogenic diet, they are omnivores and they do eat carbohydrates, so their standard fuel source for the brain and body is not ketones. However, I found that by taking Ketone IQ, which we know increases blood ketones, I can achieve much better focus for longer periods of time, for any kind of cognitive work, and much greater energy levels for exercise, especially if I'm going into that exercise fasted and find myself a little bit hungry when I start that exercise. And this is no surprise. We know that ketones are the brain's and body's preferred fuel source, even if you're not following a ketogenic diet. So, in other words, I and many other people are now starting to leverage endogenous ketones as a fuel source for the brain and body, and yet we are not following a ketogenic diet. And, of course, if you are fo- following a ketogenic diet, Ketone IQ will further allow you to increase your blood ketones as a source of brain and body fuel. If you'd like to try Ketone IQ, you can go to HVMN.com/huberman to save 20% off your order. Again, that's HVMN.com/huberman. The Huberman Lab Podcast is now partnered with Momentous Supplements. To find the supplements we discuss on the Huberman Lab Podcast, you can go to Live Momentous, spelled O-U-S, livemomentous.com/huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's livemomentous.com/huberman. And now for my discussion with Dr. Peter Attia.
- 7:34 – 10:54
Lifespan vs. Healthspan
- AHAndrew Huberman
Dr. Attia, Peter, welcome back.
- PAPeter Attia
Thanks, man. Good to be back, and sounding better this time.
- AHAndrew Huberman
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.
- PAPeter Attia
So, I mean, I think you, um, have to be mindful of how you define these terms, and, uh, I'm not gonna 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. So it involves some bifurcation between lifespan and healthspan. Uh, lifespan is very easy for people to understand. It is binary, you are alive or you are not alive. And, uh, clearly part of longevity is about how long you live. Uh, now I think for a lot of people, that tends to be where the discussion ends. That tends to be the focus of it, right? It's sort of like, you know, longevity somehow implies living for, you know, 100 years, 120 years, some- something to that extent. We talk a lot about maximum lifespan, um, e- even in laboratory experiments with mice, that's sort of one of the metrics that's, that's discussed is what's, what's maximal lifespan of the animals. Um, but there's an equally, if not slightly I think potentially more important part of longevity, which is healthspan. And healthspan is squishier, and I think it requires some definition. Now, the, the medical definition of healthspan is the period of time, uh, by which you are free from disability and disease. Uh, I find that to be a not particularly helpful definition, because by that definition, you and I have the same healthspan today that we did 30 years ago. But I know you pretty well, you know me pretty well. 30 years ago, we were twice the men we are now based on what we believe our healthspan is, right? In terms of our cognitive function, our physical performance, and things like that. So, you know, I've clearly experienced a deterioration of my physical function, as I'm sure you have going back to when you were a teenager, late teenager, early 20s, and I think that needs to be captured somehow in healthspan. So, the way I think of healthspan really is along these three dimensions, physical, cognitive, and emotional. Again, not necessarily suggesting that that's the only way to do it, but I do think that clinically it makes the most sense. And so therefore, anything that really becomes a question of longevity has to address all of these issues, lifespan, physical health beyond that of just straight up disability and disease, cognitive health independent of and separate from pathology, such as dementia, and emotional health, which of course is by far the most complicated of all of these, because we have no biomarkers for it. We have no, you know... Y- it's not like you can get a scan on somebody and determine the state of this. Um, but nevertheless, it's, it's important, right? And it dramatically factors into quality of life.
- 10:54 – 14:44
“4 Horseman of Death”, Diseases of Atherosclerosis
- PAPeter Attia
- AHAndrew Huberman
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, the binary one, dead or alive, right?
- PAPeter Attia
Yeah.
- AHAndrew Huberman
I think 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, uh, how can people stay on the, uh, freeway of life, so to speak?
- PAPeter Attia
So this is, again, a great analysis. We internally, uh, 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. Um, so if you simply just look at actuarial data, which are readily available through the CDC, and do a little bit of data, you know, manipulation and analysis, you can pretty quickly realize what the horsemen of death are, 'cause there's largely speaking kind of four horsemen of death. Um, the first and most c- uh, consequential in terms of the numbers is the diseases of atherosclerosis. So that's, um, cardiovascular disease being the lion's share of that, but also cerebrovascular disease.So anything that has to do with atherosclerosis rises to the top. Now, that's- that's true in the United States, but it's even more true outside of the United States. It's even more true globally. So in other words, when you look at the relative difference between the number one cause of death in the US and number two, which is cancer, um, the gap is actually smaller in the US than globally. Globally, it's enormous. We're talking about 18 to 19 million people a year that are dying of atherosclerotic cardiovascular disease in the world, whereas number two is cancer at about 11 million.
- AHAndrew Huberman
How does the number change when you include, um, cerebrovascular disease?
- PAPeter Attia
Yeah, it adds, it adds a bit to it. Um, cerebrovascular disease has, there's largely speaking, you can die sort of through embolic events, which are the majority of them. Those-
- AHAndrew Huberman
Could you explain for people w- what embolic events are?
- PAPeter Attia
Yeah, so taking a step back, with like... What- 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, uh, devastating. And it's devastating in a more readl- you know, readily apparent fashion than virtually any other organ. Um, so one way that that can happen is if a clot or disruption of blood flow occurs through obstruction of blood flow. So- so that can occur through a clot. So for example, if a person has atrial fibrillation and a blood clot gets festering in the right atrium, and they happen to have a hole in between the, you know, atria of their hearts, called a patent foramen ovale, and a clot goes from right to left, it can make its way up into the, uh, arterial circulation and- and- and happen that way where you occlude blood flow. The much more common way it occurs is the same way it occurs in the heart, which is you have plaque buildup and that plaque becomes unstable, that plaque ruptures, and the rupture of that plaque results in an immediate attempt by the body to fix the problem. But in doing so, it walls off the artery, meaning the blood flow distal to that point, so that, you know, now blood is acutely being robbed of that. However, there are other ways that people can, um, have this problem. And so you have the whole hemorrhagic side of this. So you can have blood vessels that... You know, small blood vessels in the brain that will rupture as a result of high blood pressure, for example. So hypertension factors both, into both sides of this equation, um, both in the heart and in the brain. Uh, the majority of these are embolic, however, so don't quote me on this exactly, but call it four or five to one strokes result from an embolic phenomenon as opposed to, um, a hemorrhagic phenomenon, a bleeding phenomenon.
- 14:44 – 23:14
Tool: Hypertension & Stroke, Blood Pressure Testing
- PAPeter Attia
- AHAndrew Huberman
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, uh, bleeders, as they're sometimes called, or clotters. So things like, uh, factor V Leiden mutations, uh, which can be exacerbated in women, for instance, by taking certain oral contraceptives. I mean, they... And there's huge lists. If people are interested in them, they can look up, you know, what are the factors, uh, controlling, uh, bleeding and, uh, predisposed people to being a clotter. But for the typical person out there who feels healthy, um, but might do well to know whether or not they are predisposed to be a bleeder or a clotter, (laughs) um, what- what sorts of things rise to the top of that list and that people might want to check into?
- PAPeter Attia
Well, uh, I mean, there might be sort of two different things going on in, 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 blood pressure. Blood pressure would be the first, second, and third driver of that. So hypertension is hands down the leading driver of hemorrhagic stroke phenomenon.
- AHAndrew Huberman
Okay, so I'll just, uh, briefly interrupt and ask, um, 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?
- PAPeter Attia
Well, I'm, I actually find myself, uh, quite in line with the most recent available data on blood pressure. And this has been, um... Obviously it's 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 pressure trial, the data are becoming clearer and clearer that the more aggressively you manage blood pressure to be within the 120 over 80 range, the better. So, you know, there's a recent study that even looked at going from what used to be considered acceptable, which was 130 to 135 over 80 to 85. We used to basically say that's kind of the first level of hypertension, and we would say, "Well, you know, do you really need to be better than that?" And the answer turns out to be, yes, you do. If you want to reduce heart attacks and strokes, be, it's better to be 120 over 80 than 135 over 85. Now, this is a whole other rabbit hole that we don't need to go down, but it's a total obsession of mine, which is, how do you measure a person's blood pressure? I think this is potentially... I'd have to give it thought, but honestly, I could say top three underdiagnosed fixable problems in the United States today, and probably globally. In other words, there are too many people walking around with high blood pressure who don't know it. Um, and I think part of the problem is, it's something that is mostly done in the doctor's office, and the readings that you get in the doctor's office can be often misleading. You, you've heard of this phenomenon of white coat hypertension. So you go to the doctor, your blood pressure is virtually never measured correctly in the doctor's office.
- AHAndrew Huberman
That cuff they put on and that, that-
- PAPeter Attia
Yeah.
- AHAndrew Huberman
... squeeze bulb that's not-
- PAPeter Attia
Yeah, if you-
- AHAndrew Huberman
... not accurate.
- PAPeter Attia
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.
- AHAndrew Huberman
Okay, folks, so when you go to the doctor's now, you don't let them-
- PAPeter Attia
Don't let them-
- AHAndrew Huberman
... take your blood pressure-
- PAPeter Attia
... take your blood pressure on the day-
- AHAndrew Huberman
... until you've been sitting for five minutes. And that doesn't include in the waiting room, because if you walk from the waiting room-
- PAPeter Attia
Right, because then you get up and walk over, right.
- AHAndrew Huberman
Okay, so make them stand there.
- PAPeter Attia
Right. So you, you want to be sitting there like this. Um-... 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, you know, using the human ear to listen, which, believe it or not, you would think a machine is better, but it's not. The machine can be misled by different sounds. Now, I don't want to suggest that automated cuffs are useless, they're not, but when an automated cuff gives you an answer that is, you know, potentially suspect, always back it up with a manual. I'm pretty relentless about checking my blood pressure and, um, so I'll do side to side manual versus automated every day, and there's easily a 10 to 15 point difference between them.
- AHAndrew Huberman
Maybe this is a silly question, but can people check their own blood pressure?
- PAPeter Attia
Uh, meaning manually?
- AHAndrew Huberman
Yeah. Just could, could I get a, get a-
- PAPeter Attia
I mean-
- AHAndrew Huberman
... cuff and a bulb and, and learn how to do it?
- PAPeter Attia
Yeah, I think so. I mean, I can do it, but honestly I usually have my wife do it. She's a nurse. Um, but it's not rocket science to check blood pressure. I, 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 cuff I have is really easy to use. Like it's, once you put it on, you know, it's in a single thing. I'm squeezing the bulb and looking at the pressure gauge while I've got the, you know, um, uh, stethoscope on my artery.
- AHAndrew Huberman
I mean, given the importance of blood pressure and this arterial sclerosis being at the top of the list of, uh, risks for (laughs) um, dying, um, it seems to me it might be worth the expense. What, what's a typical range of cost for, for the quality of-
- PAPeter Attia
I, I, I don't ... It's not, it's not inordinate.
- AHAndrew Huberman
...
- NANarrator
That makes sense.
- PAPeter Attia
Like, I feel like my blood pressure cuff is 40 bucks, um, and the stethoscope is a couple of hundred bucks if you're getting a good one. And, um, you know, a good automated cuff, there's ... I, my, I have no affiliation with any of these companies. I use a, I use two automated cuffs. One's called Withings and the other one's made by a company called Omron, O-M-R-O-N, um, and they're both decent. But again, they tend to run high, and I have yet to find a credible explanation from cardiologists as to why. Everybody acknowledges that the manual one, when done correctly, is the answer, but I've heard wonky answers about why automated ones are sometimes incorrect. And again, it's just made me realize, we're not checking blood pressure often enough on people. We're overly relying on blood pressures in the doctor's office which are not being done correctly, so we basically have our patients do this relentlessly.
- 23:14 – 32:24
Preventing Atherosclerosis, Smoking & Vaping, Pollution
- AHAndrew Huberman
I don't want a stroke. I don't want to bleed in the brain. Um, I don't want a clot. Um, 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?
- PAPeter Attia
Yeah. So there's three big ones that stand out, you know, top and center, and then there's kind of a fourth one that I think is the, 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 smoking and blood pressure are both devastating for arteries, uh, but for different reasons, right? So smoking is devastating from a chemical perspective, so it's completely irritating to the endothelium. So the endothelium, as you know, is the single cell lining that is the innermost part of the arterial and arterial wall. So this is a pretty special organ. Um, again, it's, it's, it's a bit naive but understandable that people just think of arteries as tubes. Um, they're much more complicated than that. They have many layers to them, but this particular layer-... is unusually important. It has an outsized importance, because it is the one that's in contact with the luminal side, right, where the blood is flowing in the tube, and anything that injures that has significant consequences. So smoking is irritating to that in a chemical way, and blood pressure is irritating to that in a mechanical way. So tho- those two things basically you just want to... Th- that's the low-hanging fruit in my world, right? You just don't want to have those things causing irritation to the endothelium, because that renders you now susceptible to the third factor, which is ApoB-bearing lipoproteins.
- AHAndrew Huberman
I want to talk about ApoB, um, in depth, but as long as "Don't smoke" is the second recommendation on the list, uh, can we better define, um, smoking, uh, and what's being smoked? So assume nicotine for-
- PAPeter Attia
Right.
- AHAndrew Huberman
What about cannabis, and what about vaping of nicotine and cannabis? Because vaping has become so much more common.
- PAPeter Attia
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, you know, let's consider a person who smokes a pack a day for 20 years. We call that a 20-pack-a-year smoker. Someone who smokes two packs a day for 15 years is a 30-pack-a-year smoker. That's a person who's dramatically increased their risk of, uh, many cancers, including lung cancer, and also their risk of cardiovascular and cerebrovascular disease. Again, I'm not a, I'm not a THC guy, so I don't, I can't necessarily speak for the habits of people that are smoking marijuana. I can't imagine they're smoking that much.
- AHAndrew Huberman
Probably not.
- PAPeter Attia
Yeah. So, so while on a, on a joint to cigarette basis, they're probably equivalent in terms of harm, it... I don't know. Let's say a person smokes a joint a day. That would be like smoking a cigarette a day. You know, that's a twentieth of a pack. Again, I don't want to say that there's no downside to that, but it- it- it's, it's probably significantly less. So I don't, I don't think the risk fully tracks. I think the same is probably true for vaping. And I, I want to be clear. Like, I don't think vaping's a good idea. My, my, you know, the last time I looked at the data on this, it was surprisingly sparse, but to me, the only advantage I could see to vaping was if it was the only way a person would stop smoking. So there was... You know, I sort of looked at it as it was the, definitely the lesser of two evils, but the, by far the better scenario was not to do any of these things. If, if nicotine is what you're after, there are better ways to get nicotine, for example-
- AHAndrew Huberman
Yes.
- PAPeter Attia
... through lozenges and gum and things like that. So that, you shouldn't be turning to those things to, to do it, but, but if it was like, if gum is here and cigarettes are here, you know, vaping was probably here. But boy, I don't know.
- AHAndrew Huberman
For those listening, uh, uh, Peter spaced his hands far apart for, um, gum and smoking and put vaping about a third of the way be- uh, from gum, uh, toward, uh, smoking. In other words, vaping isn't good for you, but it's not as bad as smoking.
- PAPeter Attia
That would be my, that would be my... I mean, do you have a... You've probably looked into this as well. What, what are your views on this?
- AHAndrew Huberman
Yeah, we did an episode on nicotine. I did an episode on cannabis, and, um, you know, the, the discussion around cannabis gets a little contentious for reasons that aren't, um, 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," which is a crazy argument, right? Getting hit by a bus isn't nearly as bad as getting hit by a motorcycle in most cases, but sometimes... You know, so that's just kind of silly, yeah. Um, and clearly cannabis has medical applications.
- PAPeter Attia
Yeah.
- AHAndrew Huberman
Clear- clearly. Um, and then it becomes an issue of the ratio of THC to CBD, pure CBD forms actually being quite effective for the treatment of certain forms of epilepsy.
- PAPeter Attia
Yeah.
- AHAndrew Huberman
So-called Charlotte's Web. That's actually what it's called. Um, very high THC-containing cannabis clearly predisposes especially young males to later onset psychosis. Those data are starting to become clear, clear enough to me anyway that people ought to be aware of them at least, and maybe make decisions on the basis of those. When it comes to the smoking versus vaping, it's just very, very apparent that the chemical constituents of the vape and what people are inhaling are terrible for people, and are loaded with carcinogens and a bunch of other stuff, many of which cro- cross the blood-brain barrier. So that's what worries me the most.
- PAPeter Attia
Mm-hmm.
- AHAndrew Huberman
You know, obviously I'm not a clinician, but anytime I hear about small molecules that, you know, these small inorganic molecules getting across the blood-brain barrier and then being maintained in neurons for many, many years, I worry because the experiment is ongoing mostly in young people. So anyway, without going too far down that track, I, I think if people can avoid smoking and vaping, they should. And as you mentioned, there are other delivery devices for nicotine and cannabis, tinctures and-
- PAPeter Attia
Yeah.
- AHAndrew Huberman
... patches and, uh, gums and things that, um, edibles that, um, if people choose to use those substances, they can offset-
- PAPeter Attia
Yeah, and I think, I think sometimes people would benefit to, to imagine what the surface area of the lung is, right? If you took the alveolar air sacks of the lungs and spread them out, you would easily cover a tennis court.
- AHAndrew Huberman
Remarkable.
- PAPeter Attia
So, so-
- AHAndrew Huberman
Yeah.
- PAPeter Attia
... just think about any time 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 any time you're putting something else in that wake, you're doing a really good job of getting it into your body. So be mindful of what that is, um, and, and that... Look, that applies to, to pollution too. I mean, the, the PM2.5 data is pretty good.... I, I think once you s- so particulates that are less than 2.5 microns are, are getting straight into the body, um, which is, like, a great argument for a- avoiding air pollution, right? I mean, I, I, I always find it funny, not to get off on this tangent, but to me the most compelling arguments around cleaner energy have nothing to do with greenhouse gases. They have to do with air pollution.
- AHAndrew Huberman
Mm-hmm.
- PAPeter Attia
I promise you, more people are dying from the particulate matters in air that result from burning coal than are ever going to die from the CO2 emissions that result from that. And it's not, it's, and it, and, and I would argue that's gonna be two orders of magnitude. It's not even in the same zip code.
- AHAndrew Huberman
That makes sense. During the fires, uh, which seem to follow me, uh, (laughs) because when I was in Northern California-
- PAPeter Attia
(laughs)
- 32:24 – 33:29
Sponsor: AG-1 (Athletic Greens)
- PAPeter Attia
- AHAndrew Huberman
I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, 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 reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins and minerals that make sure that all of my foundational nutritional needs are met, and it tastes great. If you'd like to try Athletic Greens you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll
- 33:29 – 42:21
Cholesterol, ApoB
- AHAndrew Huberman
give you a year's supply of vitamin D3K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3K2. So trying to avoid artero- scler- ar- (laughs) it's such a difficult word to say, especially for a neuroscientist, arterial sclerosis. Did I get it right?
- PAPeter Attia
Well, it's athero which is easier 'cause yeah.
- AHAndrew Huberman
Atherosclerosis. Oh there. Okay.
- PAPeter Attia
Yeah. It's, it's much easier.
- AHAndrew Huberman
I've been making life more complicated for myself. Typical of me. Okay, um, so blood pressure keeping it-
- PAPeter Attia
Yeah.
- AHAndrew Huberman
... 128, oh, 120/80 or better. Don't smoke. Let's just throw in don't vape.
- PAPeter Attia
Sure.
- AHAndrew Huberman
I'm gonna just plant my flag on it.
- PAPeter Attia
I, I, I, I, I'm with you.
- AHAndrew Huberman
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?
- PAPeter Attia
Okay, so to explain this you have to tolerate a little bit of chemistry. Um, so everybody's heard of cholesterol, and, uh, I, I, 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 and there was a thought that, "Hey, this is a bit more technical than it needs to be." But I, I think that sometimes you do need to resort to longer dissertations to dispel mythology. So cholesterol is a lipid. It is a molecule that the body synthesizes. It is a molecule that is essential for life. So if you cannot synthesize cholesterol, you can't live. You, you'll die in utero. So there are rare genetic conditions that prevent the successful synthesis of cholesterol. Uh, you know, embryos that have those mutations do not survive. Okay, so why do we need this stuff? So we need this stuff primarily for two reasons. First, it makes up a very important structural component of cell membranes. So as you know, a cell is a sphere. We, we look at them and think they're circles but they're spheres, and they're fluid, right? They, they, they aren't just like little perfect, you know, big bowling balls or, you know, balloons. They actually morph and shape and move in these paths, and this is what, sort of allows cells to be next to each other and all sorts of things. They also have channels across all of them, and those channels are held in place by, among other things, cholesterol and phospholipids. The second thing that makes cholesterol so important, it is the precursor to some of the most important hormones in our body. So our sex hormones, testosterone, estrogen, progesterone, in addition to glucocorticoids, if you look at them it's really funny, you know, people if you're looking, if you Google like give me the structure of these things, you're kind of like wow, they're all basically the same. They all look really similar and they're all pretty much just templates of cholesterol. So understandably when it's something that's that important, the body would leave nothing to chance. We make all of our own cholesterol. The cholesterol that you eat in food...... largely irrelevant. It's esterified cholesterol, so it means it has an ester side chain. It's too bulky to absorb in the gut, so most cholesterol that you eat in food just goes out your GI tract. Okay, so we have this super important molecule that every cell in the body makes, but there's a bit of a problem. There's actually two problems. The first problem is not every cell can make as much as it needs all the time, so you have this demand problem. So for example, if you're sick, you're gonna need to make far more glucocorticoids. Your body's response is going to be to ramp up cortisol production to mobilize fuel and do a whole bunch of other things, and certain cells, like the adrenal glands, are gonna be called on to rise to a higher level of performance, and they're not gonna be able to make enough cortisol. So they're going to have to borrow or take cholesterol from other cells in the body. In fact, one of the things we used to notice in the ICU, I never knew why it was happening, I now know, is the few times I would accidentally order the wrong set of labs on a patient in the ICU and also order, like, a lipid test or something, you would always notice their cholesterol levels were dropping. You know, serum cholesterol levels. And I now realize why, because they were basically just funneling cholesterol to the adrenals to make more of the cortisol that they needed to combat whatever they were in the ICU for, which is usually the most severe form of, you know, stress the body is under. So you have to be able to transport this stuff, and then the second problem is, as you know, cholesterol, being a lipid, is not water soluble. So the, the most dominant highway in the body is the circulatory system. We, we can use the lymphatic system and things like that, but for the most part we use our circulatory system as the highway to move stuff around, and the highway is made up of water. Plasma, which is what you're... is the liquid component of your blood, is water, and therefore things that are water soluble move easily. So glucose, uh, sodium, electrolytes, all of those things are dissolvable in water and therefore they don't need a carrier. You just dissolve them in the water and they can go. So that's why your liver can make glucose that your brain can easily get and there doesn't need to be a carrier or an intermediary or anything like that. But unfortunately with cholesterol being a lipid, we can't do that. Just as water and oil don't mix, cholesterol and plasma don't mix. So the body had to come up with a trick, and the trick was designing a vehicle that was water soluble on the outside and fat soluble on the inside, that you could bury the cholesterol inside along with triglycerides, and on the outside it was covered in protein, which is water soluble, and that's the, that's the thing that moves around, and that thing is called a lipoprotein, and as its name suggests it's part lipid, part protein, lipid on the inside, protein on the outside. And those lipoproteins, um, come largely in two different families. Uh, so one family comes from a lineage called ApoB. So the ApoB family, which is short for apolipoprotein B100, is a family that is derived from the liver, and each of those lipoproteins has one and only one apolipoprotein B100 on it. We shorten it and just call it ApoB 'cause we don't really worry about apolipoprotein B48, which is a sat attached to chylomicrons that are responsible for fat absorption in the gut. They're very short lived. They don't really factor into atherosclerosis, so we're gonna just, for the purists out there, there's an ApoB48. We're not gonna talk about it. So (clears throat) when I say ApoB what I'm talking about is a protein that wraps around a subset of these lipoproteins. There's another family of lipoproteins called ApoA or apolipoprotein A. This is a much more complicated family, and I'm not gonna talk about it here 'cause we're, we would take an hour to just explain how the apolipoprotein A family works, but I'll, I'll, I'll, again, the punchline is there are many apolipoprotein As, there's variable numbers of ApoAs on those proteins, and they are all part of a family called high density lipoproteins. Back to the ApoB guys, they are of the low density lipoprotein lineage. So you've heard the term LDL and HDL, what is it referring to? It's basically referring to the relative concentrations of protein and lipids in the lipoproteins, and not surprisingly based on their names, the HDLs are higher density, more protein, less lipid, the LDLs, low density lipoproteins, and VLDLs, very low density lipoproteins, and IDLs, inter- intermediate density lipoproteins, are all lower density, which means more lipid to protein. There are different sizes. There's a whole bunch of other things going on. The most important fact in all of this is that the ApoBs are atherogenic. So what we're about to talk about next is perpetuated by lipoproteins that have an ApoB on them. So everything in the story right now is just about how do you get cholesterol around the body.
- AHAndrew Huberman
Mm-hmm. And these, um, proteins that have lipid in the middle, um, so let's just take ApoB, for example, um, many, many billions of them floating around in our body, even in the healthiest of people.
- PAPeter Attia
Yep.
- AHAndrew Huberman
Um, and they're being shuttled to tissues that need them, um, like the adrenals, muscle, heart, et cetera.
- 42:21 – 49:29
Cholesterol Levels, LDL & ApoB Testing
- AHAndrew Huberman
W- what sets the demand for these things? So for instance, could somebody have relatively high, um, LDL, uh, maybe even higher than, um, sort of o-... high end of chart or even, um, above high end ApoB, but there's some sort of demand, metabolic demand or, or they're, they're weight training a lot or they're running marathons and so they need a lot of LDL. The reason I ask this, um, is because it's so easy for the uninformed person, which I include myself in that group, to just think here, "Oh, LDL bad, cholesterol bad, ApoB bad," when in fact, um, you very graciously spelled out the fact that they- these things actually perform a f- a functional role in the healthy body. So before we get into why they ar- are or can be bad, why would you want a low density lipoprotein? What is that doing for somebody and is there, um, any circumstance where the way people are exercising or thinking or not sleeping or sleeping too much, it's, um, that a higher level actually reflects a, a healthy metabolic need?
- PAPeter Attia
We don't have any evidence of that to date. Um, all of the functions that I described can be functio- can be done by the HDL. So the high density lipoproteins, the ApoAs can do all of it.
- AHAndrew Huberman
So ApoB and low density lipoproteins are just, um, th- they're just the necessary, uh-
- PAPeter Attia
We don't actually-
- AHAndrew Huberman
... th- the waste? I mean, I, I-
- PAPeter Attia
No, we don't understand why we have them, Andrew. This is the part that's really interesting to me. Um, most species do not even have ApoB. And as a result of that, most species are chemically incapable of atherosclerosis.
- AHAndrew Huberman
So if someone could zero out their ApoB and their LDL, y- we assume they would function just fine?
- PAPeter Attia
We know they would because we have certain people who walk around with genetic mutations that render them that way.
- AHAndrew Huberman
Wow. Okay.
- PAPeter Attia
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. It's an understandable thing, right? You, you could speak to this very eloquently, the role of cholesterol in the brain.
- AHAndrew Huberman
Yeah, I wrote down when I, um, was a post-doc at Stanford, um, as I always point out, I was born at Stanford, trained at Stanford, ƒI probably die at Stanford, hopefully a long time from now.
- PAPeter Attia
We're gonna try to-
- AHAndrew Huberman
You'll tell me how long from now, by the end of the episode.
- PAPeter Attia
Well, we're gonna do the Charlie, we're gonna do the Charlie Munger thing-
- AHAndrew Huberman
(laughs)
- PAPeter Attia
... and make sure that you never go back to Stanford so that, like, you can't die there.
- AHAndrew Huberman
There, exactly.
- PAPeter Attia
(laughs)
- AHAndrew Huberman
We... Cured already. Um, the, when I was a post-doc, I worked with a guy named Ben Barres who I, I know, um, you know probably, um, as a different person then, uh, for reasons that people can look up Ben's name. Um, anyway, incredible scientist and, but there was someone in his lab that discovered that cholesterol is a critical component of the synaptogenesis process, the form- the formation of connections between neurons in the developing brain. And then, uh, that we- went on to lead to the discovery of things like, um, thrombospondins being important for synaptogenesis, et cetera. But cholesterol sits central in the brain development mechanisms. Like you, you want cholesterol around-
- PAPeter Attia
Yeah.
- AHAndrew Huberman
... for brain development. In fact, I think very low fat diets and very low cholesterol diets during early development can really impair brain development, as I understand it.
- PAPeter Attia
Yeah, it's not, 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 v- very low levels of cholesterol. They would have, uh, and I should explain one thing that's important-
- AHAndrew Huberman
Oh, they're not myelinated yet, right? I mean, they're, they're, uh, sorry to interrupt, but the, uh, myelin of course, the, the sheathing around, uh, uh, neuron, neuronal axons, i- at which accelerates the propagation of nerve signals and which is deficient in things like multiple sclerosis is essentially fat made up of phospholipid, um, and requires cholesterol for synthesis. But, but young children are not very well myelinated. I mean, the spinal cord is myel- uh, you know-
- PAPeter Attia
Right, so, so, so-
- AHAndrew Huberman
... spinal tracts are myelinated, but-
- PAPeter Attia
... this is what's interesting, right? We would all agree that cholesterol is more important to infants and children than to anybody else, right? It would be the most important substrate for CNS development, and yet infants and children have virtually unmeasurable levels of cholesterol. It really starts to take off in your teenage years, right? So cholesterol basically, serum cholesterol levels rise basically monotonically throughout life. Um, (clears throat) women get a big bump at menopause, so it really goes up for them. Um, but what's interesting is how is it, how do we reconcile the fact that infants and children have really low levels of serum cholesterol yet clearly undergo CNS maturation without any problems? And it basically comes down to the following: what you measure in the serum is but a fraction of the total body pool of cholesterol. So we get a little bit of a, the light under the, you know, the, uh, what's the, the, you know, the, the street lamp under the-
- AHAndrew Huberman
The drunk under a light-
- PAPeter Attia
The drunk-
- AHAndrew Huberman
... lamppost-
- PAPeter Attia
... or the street lamp problem-
- 49:29 – 1:01:06
ApoB Levels & Atherosclerosis, Causality
- AHAndrew Huberman
ApoB level is your red flag cutoff, right? Um, I actually had my ApoB measured recently, and I'm definitely above the high end, so-
- PAPeter Attia
Well, we'll be discussing this over dinner on Saturday night.
- AHAndrew Huberman
Yeah. (laughs)
- PAPeter Attia
(laughs)
- AHAndrew Huberman
And w- um, and, uh, just to tie this back, um, I hope that's a steak dinner. And that should be fine given the fact that dietary cholesterol has no direct link ApoB and LDL.
- PAPeter Attia
That's true, but dietary saturated fat does.
- AHAndrew Huberman
Ah, okay, so I'll-
- PAPeter Attia
Which is not to say we're not gonna have a steak.
- AHAndrew Huberman
Right.
- PAPeter Attia
We will, but I, I just-
- AHAndrew Huberman
Not necessarily one of the fattier cuts. Um... Although probably will be, uh, for me. Um, so what's, what's the high end that you, uh, 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.
- PAPeter Attia
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 it. That- those are your choices. Statistically speaking, more people will die from it than anything else. But if you live long enough, we will all die with it to some extent." So, if you're me, and I come from a family history, as you know, I write about this in the book, where basically every man in my family except one has died of atherosclerosis, and they have all done so very prematurely. Uh, my dad's lost brothers in their 40s and 50s. Um, by some miracle, my dad is still alive at 86, but, you know, I think that's in large part because he at least had the good sense to listen to doctors and take medication to lower his cholesterol and blood pressure. Um, if your objective is to not die from heart disease and only to die with it, then you want ApoB as low as possible. Now, how low you go depends on when you start, because one way to think about this is it's an area under the curve problem. The longer you wait to start doing something about this, the more aggressively you need to do something about it. Um, I think a better way to think about this, though, is to go back to what we talked about with smoking. So, would you agree that smoking is causally related to lung cancer?
- AHAndrew Huberman
Yes.
- PAPeter Attia
So just to be clear, Andrew, you do not think that it's just an association that smokers get more lung cancer?
- AHAndrew Huberman
No, I do not.
- PAPeter Attia
Y- in other words, you believe that smoking causes lung cancer, then?
- AHAndrew Huberman
Yes.
- PAPeter Attia
Okay.
- AHAndrew Huberman
I mean, there are a number of mechanistic-
- PAPeter Attia
A number of things that can-
- AHAndrew Huberman
... steps in, in between.
- PAPeter Attia
Yes, yeah. Yeah, yeah.
- AHAndrew Huberman
I mean, if somebody was really wanting to get, uh, to, you know, drill into the logic, they could say, "Okay, it's not actually the smoking." It's a, you know, some, uh, uh, disruption of the endothelial cell lining that, you know, led i-
- PAPeter Attia
But, but smoking triggers that that l- triggers that.
- AHAndrew Huberman
I assume so.
- PAPeter Attia
And I agree with you-
- AHAndrew Huberman
Yeah.
- PAPeter Attia
... by the way. I think the data are very clear.
- AHAndrew Huberman
I'm very relieved to hear that.
- PAPeter Attia
Yeah, yeah. I'm-
- 1:01:06 – 1:12:30
ApoB Reduction, Insulin Resistance, Statins, Ezetimibe, PCSK9 Inhibitors
- AHAndrew Huberman
ApoB is, you know, 80, 100. 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? And if so, what are the more c-common forms of prescription medication that work best? What are their side ef- effect profiles, and so on?
- PAPeter Attia
So, eh, yeah, usually once you want to start getting down into the 30 to 60 range, you're gonna 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, will bring this down, right? So, one of the hallmarks of insulin resistance is elevated triglycerides. They haven't even talked about triglycerides, but (clears throat) they, they warrant some attention, because I mentioned it earlier, but one of the other things that the lipoproteins carry is triglycerides. So, they're, you're carrying fat and cholesterol. And if you recall, ApoB represents the number of particles. So, the purpose of them is to be carrying around mostly cholesterol, but if you have a high amount of triglyceride, you're basically using up cargo space on the ships, and so you need more ships. So, if a person has elevated triglycerides, and I consider anything over 100 to be elevated, even though most laboratory tests would consider normal to be up to 150 milligrams per deciliter. Um, we would want to fix their insulin resistance, bring the trigs way down. Uh, I, I would want to see trigs no more than two times the HDL cholesterol. So, if their HDL cholesterol is, you know, 60 milligrams per deciliter, I consider 120 to be through the roof high, and ideally, we want trigs at or below HDL cholesterol. So-
- AHAndrew Huberman
Trigs being triglycerides.
- PAPeter Attia
That's right.
- AHAndrew Huberman
So, and, uh-
- PAPeter Attia
And that's, that's basically a big nutrition-
- AHAndrew Huberman
... does that mean lowering dietary fat?
- PAPeter Attia
No. Actually, it's most easily accomplished through carbohydrate restriction. Yeah. Carbohydrate... Eh, 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, um... Even e- even under eucaloric conditions, carbohydrate restriction will lower triglycerides. So, again, energy restriction would be kind of first order of business, um, but within that, carbohydrate restriction will probably get you there quicker. So, you know, you sort of take the, the low-hanging fruit off the table.
- AHAndrew Huberman
And where does exercise come, um, play a role?
- PAPeter Attia
Minimal role. Yeah.
- AHAndrew Huberman
For improving insulin sensitivity?
- PAPeter Attia
No, no, no. I'm sorry. For improving, uh-
- AHAndrew Huberman
Ah.
- PAPeter Attia
... lipids in general. Yeah.
- AHAndrew Huberman
Okay.
- PAPeter Attia
It, it, it-
- AHAndrew Huberman
But it can improve ins- uh, insulin sensitivity.
- PAPeter Attia
It can, it can... Absolutely. Yeah. Yeah.
- AHAndrew Huberman
Especially combinations of resistance training and cardiovascular exercise?
- PAPeter Attia
Yeah.
- AHAndrew Huberman
Correct?
- PAPeter Attia
Yeah.
- AHAndrew Huberman
Yeah.
- PAPeter Attia
So, once it comes down to pharmacotherapy, um, 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, um, both directly and indirectly on the problem. So, directly, they work by targeting an enzyme, um, very high in the synthetic pathway of cholesterol production. Uh, an enzyme is called HMG-CoA reductase, and I think it's the second committed step. I might, I could be wrong on that. It's, I don't think it's the first committed step. But you, that, that enzyme gets targeted kind of ubiquitously throughout the body and in response to that, the liver senses a reduction in the body's pool of cholesterol. And the liver really tries to regulate this, so the liver, in response to that, increases its expression of LDL receptors. So, the liver itself has LDL receptors on its surface, and as the body's pool of cholesterol goes down, the liver senses this reduction and says, "I want to bring more cholesterol in." More LDL receptors go up and more ApoB particles are coming out of circulation. So, that's really the dominant way that they work. And in fact, that's kind of the dominant way that all of these drugs work. So, another class of drug is called Ezetimibe. It works by blocking, I mean, we can get as technical as you want on this, it's called the Niemann-Pick C1 like 1 transporter in the enterocyte. Um, I like to explain this, I borrow this explanation from Tom Dayspring, but the enterocyte is, eh, is obviously the luminal gut side cell that is responsible for absorption of cholesterol. Remember I said earlier, most of the cholesterol you eat, you don't absorb. The reason you can't absorb it is an esterified cholesterol molecule cannot come in the Niemann-Pick C1 like 1 transporter. It's too, it's physically too large. But the cholesterol that you synthesize, which once it makes its way back to the liver gets secreted in bile down the intestine, that is unesterified and readily fits into that transporter. So, I kind of describe that guy as the ticket taker at the bar. He lets everybody in as long as they fit through the door. There's a checkpoint inside the bar that basically says, "Do we have too much cholesterol? If so, spit it out." And there's another door that acts more like the bouncer, and he's called the ATP-binding cassette G5/G8, and he spits excess cholesterol out. And if that system's working fine, everything is great, but in a lot of people that ATP-binding cassette doesn't work very well and it can't properly regulate the total body pool of cholesterol. So, there's a drug called Ezetimibe that simply blocks the ticket taker.
- AHAndrew Huberman
Are there side effects to statins and Ezetimibe?
- PAPeter Attia
Ezetimibe has virtually no side effects. It's a, you can think of it as a drug that's acting outside the body, right? It's sort of acting on, uh, you know, a turnstile door in your gut. Um, I have seen one patient get, uh, sort of loose stools from it that became enough of an issue that we discontinued it. Um, I would say that when Ezetimibe is combined with a statin, which is very commonly done, um-... it's not unheard of. I don't, I can't give you a number, but it could be as high as 10% that you see an elevation in transaminases, which are enzymes that are made by the liver in response to some irritation. So, you know, this is where I think it's unclear what the clinical significance of that is. We tend to abort the strategy in the presence of elevated transaminases. Um, even though the literature says you don't need to, our view is we have other options. Why would we tolerate any inflammation if you don't need to? Statins, uh, do have side effects. So 5% of people genuinely and legitimately- legitimately get a muscle soreness, uh, that can be debilitating. It could feel like kind of the worst workout you've ever had that, you know, like the day after you've, like imagine you hadn't lifted weights in six months and then you, you know, came over and I made you do the most brutal workout of your life. You know how you would feel the next day?
- AHAndrew Huberman
That happens every time I come over to you. Well, I work out often, um, but every time I come over to your house, you put me through the most brutal workout (laughs) I've ever been through. Uh, I think you and Cam Hanes are the two people who've managed to put me through workouts that kept me sore for at least, uh, two weeks after each visit, so.
- PAPeter Attia
So that soreness, that, imagine you would have that persisting, th- 5% of people get that response from a statin. And obviously that's just non, you know, it's a non, it's a non, it's a non-do. Um, there's a narrower subset of people that, um, do, do, do get brain fog and do experience brain frog from statins. And, and we don't really understand the why there. We have some theories as to why, you know, maybe they're, maybe they're getting too much of a reduction in central cholesterol synthesis. Um, again, it's a subjective finding, but given that we have so many tools in the toolkit, like we don't have to tolerate side effects with these drugs anymore. There was a day when, you know, you had somebody who just had a heart attack and they're basically looking down the barrel of being on a statin for the rest of their life and there were like two of them and they, you know, had tons of side effects and it, it didn't matter. Today, while there are probably nine statins out there, there are really only four that we even use, and at least two of them have such a low side effect profile. They're not as potent, but they have a, I mean, potent's a bit of a, uh, potent's the wrong word. They don't have the same effect, um, but they're very potent because you're, at least one of them you're taking at such a low dose, um, that we've got lots of statin options. The third side effect of statins, which again not common but can't be ignored, is insulin resistance. So it, it really, and this is one of the, I think one of the benefits of at least having periodic CGM tracking is we'll see this. You know, we had a patient who happened to be wearing CGM in general, and then we started him on, you know, 10 milligrams of rosuvastatin, which is probably the workhorse statin right now. It's a, that's a generic name for Crestor. Um, and he pings us like a couple weeks later and he's like, "Man, my glucose is like 10 points up consistently from where it has normally been." Kind of hummed and hawed, we troubleshooted a few things. After two months, we're like let's just stop the Crestor and, uh, see if that fixes it, and it immediately fixed it. So there was, you know, we reintroduced the Crestor and it happened again. So there was no doubt in my mind that, you know, or ver- low doubt in my mind that Crestor was responsible for that. Um, and again, you could say well maybe that's not that clinically significant, but I would argue why bother? I have other choices. So those are your two big ones. Um, the next one that is really the big one are, are PCSK9 inhibitors. So, you know, um, gosh, coming up to about 20 years ago maybe, a woman named Helen Hobbs, uh, made a discovery of a group of people that had a disease called familial hypercholesterolemia. So FH or familial hypercholesterolemia is a very genetic heterogeneous condition. Going back to that Mendelian randomization study, these are the people on the far end that show us how high lipid levels cause atherosclerosis. So these people have very high cholesterol levels, typically north of 300 milligrams per deciliter. Their LDL cholesterol alone is by definition at least 190 milligrams per deciliter. Uh, very high incidence of atherosclerosis in these people along with other sort of injuries. Like they accum- they have so much cholesterol they accumulate it in their tendons, in their eyes. I mean, it's- it's- it's a really devastating condition if not managed correctly. And she discovered this mutation in, uh, a gene for PCSK9 that codes for a protein that degrades LDL receptors. So (clears throat) these people had hyperfunctioning PCSK9 genes, so their genes were just chomping down all the LDL receptors in the liver, so these people weren't clearing LDL. About five years later, another subset of the population were discovered that were the exact opposite. These people had hypofunctioning PCSK9. They had virtually unmeasurable... These people had LDL cholesterol levels of 10 to 20 milligrams per deciliter, and not surprisingly, they had no heart disease. So that led to the development of a couple of amazing drugs that are now used. So I take one of these drugs. I've been taking one of these drugs for, I don't know, probably started in 2015. So it's an injectable drug. I take it every two weeks and it's a, called a PCSK9 inhibitor. So the drug blocks the protein and therefore gives me more LDL receptors, yanks more apo B out of circulation.
- 1:12:30 – 1:17:12
Monitoring ApoB
- PAPeter Attia
- AHAndrew Huberman
Interesting. When we were talking about side effects, I, um, I was thinking are there any short term benefits? So I guess we can call this positive side effects. But let's think of it more directly in line with the underlying biology. Let's say my apo B is, um, high, mid-range to- to high, you know, let's say 100. Um, you know, 80 to 100. Um, and I improve my insulin resistance through nutrition but we decide, you know, it doesn't go down so much so we're- we're gonna continue to- to try and knock this number down and, and I take, uh, any number of different drugs, um, to reduce it. Do I immediately start to feel better?
- PAPeter Attia
Nope.
- AHAndrew Huberman
So there's no-
- PAPeter Attia
You, you'll feel nothing.
- AHAndrew Huberman
There's... Okay.
- PAPeter Attia
You'll feel nothing.
- AHAndrew Huberman
And, and I think that's an important, um, important point because of the causality issue that we were talking about earlier. Because a lot of people are walking around out there, feeling fine. Their ApoB might be a bit high. They either know it or don't know it, but they think, "Well, I'm feeling fine." And you gave a very rational argument earlier as to why because of the causality involved, it makes far more sense to intervene.
- PAPeter Attia
Yeah. We don't want to rely on feeling when it comes to atherosclerosis. Just to put some perspective on this. When I was in medical school, we had a... And I, I think I even write about this in the book. We had a pathology lecture where the professor stands up there and he says, um, "What is the most common presentation of a heart attack?" And you know, us keener first year med students, hands shoot straight up, "Chest pain." Uh, "No. That's not the most common." Uh, "Oh, uh, uh, uh, shoulder pain, arm, radiating down the left arm." "No." "Uh, nausea." "No." "Shortness of breath." "No, no, no." We rattled this off for a few minutes and he goes, "Death. The single most common presentation for a myocardial infarction is death." More peop-... Now, I would say today, that was 25 years ago, today it's probably not the most common because, um, advanced cardiac life support is so much better, but it's still strikingly common. So-
- AHAndrew Huberman
Well, you could say that, um, the, the best predictor of a heart attack is still a heart attack. (laughs) Um-
- PAPeter Attia
Well, I mean, the-
- AHAndrew Huberman
I mean, I'm not saying that the best underlying predictor-
- PAPeter Attia
Yeah.
- AHAndrew Huberman
... but, um, and actually this hits home when I was a post-doc, I was living in San Francisco, and I'll never forget this, taking my coffee in, uh, out on my porch in the morning. This is right near the UCSF Parnassus campus. And this guy's walking down the street and he's probably about my age. And I said, "Hello." And he said, "Hello." He walked a few more steps and boom, he just hit the concrete and died right in front of me. It took a, a minute or two to know that he was truly dead. I'll never forget it because that's a-
- PAPeter Attia
Yeah, it's very traumatic.
- AHAndrew Huberman
... for, for a non-surgeon, you know, it's, it's a, it's an event, right? And they-
- PAPeter Attia
Sure.
- AHAndrew Huberman
And I followed up on this and 'cause his family, you know, the, the whole thing, um, 'cause they wanted a report and no cocaine in his system, no prior history of any kind of health issues and, but he was just strolling along and just boom, as if he'd been hit by a bus.
- PAPeter Attia
Yeah.
- AHAndrew Huberman
It was crazy.
- PAPeter Attia
So it's, I mean, again, this is just one of those things where we're going to, we're going to sp- spend a lot of time talking about things that feel good and feel bad when you change them, right? Like, if you take a person who's not sleeping well, but who thinks they're sleeping well and you ask them for a leap of faith, which is, "Hey, give me a month to help you sleep really well." Yeah, you're going to feel better. You might not know it now because you don't know how bad you're sleeping now. You've become acclimated to this. Um, but this is not one of those domains. You know, exercise, nutrition, sleep, all those things, when you do those things better, you feel better. But, uh, you know, I don't want to overpromise on this. You're, you're not going to feel better in the moment when you fix your lipids, but you'll feel better when you don't have a heart attack.
- AHAndrew Huberman
So by all this logic, everybody should get their ApoB measured. How early in life should people do that? Starting in their 20s? Uh, in their 30s?
- PAPeter Attia
Certainly if you have a family history that is of any concern. Like, in ret- like, if I could live my life over again knowing... If I knew everything, you know, then that I know today, yeah, I would have had mine measured in my 20s. You know, I didn't, I didn't get my ApoB measured for the first time probably till I was in my 40s, because, you know, that's... Well, yeah, maybe late 30s, early 40s, right? Um, I had my first calcium scan when I was 35 and I had to beg, borrow, steal to get it done 'cause everyone was like, "Why does a 35-year-old want to do this?" But I, something, I just felt something was wrong given my family history. Um, and I'm glad I did. And I'm glad I did that 'cause I learned something that, that completely changed the direction of my life.
- AHAndrew Huberman
Okay. I know my ApoB numbers and that I might be that guy who's up in the, you know, above 100, so I'm, I'm going to get this treated. Uh, that's a promise to myself.
- 1:17:12 – 1:18:30
Sponsor: InsideTracker
- AHAndrew Huberman
I'd like to just take a brief moment and thank one of our podcast sponsors, which is InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that blood work is the only way that you can monitor the markers such as hormone markers, lipids, metabolic factors, et cetera, that impact your immediate and long-term health. One major challenge with blood work, however, is that most of the time, it does not come back with any information about what to do in order to move the values for hormones, metabolic factors, lipids, et cetera, into the ranges that you want. With InsideTracker, changing those values becomes very straightforward because it has a personalized dashboard that you can use to address the nutrition-based, behavior-based, supplement-based approaches that you can use in order to move those values into the ranges that are optimal for you, your vitality, and your longevity. InsideTracker now includes a measurement of apolipoprotein B, so-called ApoB, in their ultimate plan. ApoB is a key marker of cardiovascular health, and therefore there's extreme value to knowing your ApoB levels. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman to get 20% off.
- 1:18:30 – 1:20:50
Reducing Blood Pressure, Exercise & Sleep
- AHAndrew Huberman
We covered, um, the three major risk factors which were, um, blood pressure, um, keeping that in check, don't smoke, um, and ApoB, and we've now talked about the things to adjust ApoB levels. We did not really talk about things to adjust blood pressure. I'm assuming exercise sits as one of the foremost-
- PAPeter Attia
Exercise, nutrition. Yeah. Weight, weight management is a huge one here. So, you know, you take a person whose blood... And, and this is one of those things where we don't immediately jump on the pharmacotherapy train with blood pressure, um, because here there are side effects sometimes. Um, and you do have to worry about overshooting. You don't really have to worry about overshooting a person's lipids. We do back off if we overshoot, but it doesn't cause a symptom.There's not a, there's not a short term immediate risk from doing that. If you overshoot somebody's blood pressure medication, you trade one problem for another problem. They become lightheaded when they get up to pee at night, they fall and bang their head, that's a devastating consequence, totally unacceptable. So, our goal is to see how much we can lower blood pressure without medication before we turn to medication. And let's be clear, the meds today are so much better than they used to be. Uh, again, there was a day when the side effects of these medicines were miserable. That's, that's simply not the case today. I mean, ACE inhibitors, angiotensin receptor blockers, I mean, these things are very well tolerated, especially the ARBs. Um, so again, almost anybody can be on these things, but if we could get a person to lose 10 pounds and exercise every day, uh, we see great effects with zone two stuff, right? So, kind of the low intensity cardio. Um-
- AHAndrew Huberman
What's, uh, in your recommendation there? I know you talk about this in the book, but are we t- we ... I've thrown out numbers, about 150 to 180 minutes per week. You go a bit higher.
- PAPeter Attia
Yeah.
- AHAndrew Huberman
Um ...
- PAPeter Attia
We go 180 to 250, 240. Yeah. I like to see three to four hours a week of zone two. Um, so that's an important piece, and sleep is an important piece. Um, so get, get the sleep right, get the exercise right. If you, if you're, if you're over-nourished, let's correct that problem, and if all of that doesn't work, and by the way, that works a lot of the time. No, that works most of the time. If that doesn't work, then we've got pharmacotherapy. There is still a true phenomenon of essential hypertension, which is in individuals for whom all the fixable stuff has been fixed and they still have high blood pressure, uh, we still have to medicate those folks.
- 1:20:50 – 1:23:11
High Blood Pressure & Kidneys
- PAPeter Attia
By the way, there's something that I want to mention here that doesn't get much attention, but it's so important, which is the effect of high blood pressure on the kidney and also the brain itself. We've talked about the brain, we've talked about the heart, but the kidney doesn't get enough attention. The, the kidney is a remarkable organ, and I think if you're really in this game of trying to live longer, right? If you, if you think, "Hey, you know, maybe we'll live 80, 85 years, but if we kind of start doing all of these other things and, and really optimizing our behaviors, that could be 95," well, you have to start thinking about the capacity of the kidney. And once the glomerular filtration rate falls below a certain level, uh, you have to be very careful with how you live your life. And unfortunately, this is one of those things that I, is a, is another sort of mistake that's made in kind of modern medicine, which is we don't pay enough attention to how to measure kidney function correctly. We rely very heavily on something called, um, creatinine, as opposed to looking at another biomarker called cystatin C, which is far more accurate, and we also tolerate too low of a kidney function for a person's age. So, we look at, you know, we might look at someone who's 50 whose kidney function is at 65% and say, "You're totally fine." Because it's true that at 65% there is no problem. But you're not thinking, "Well, if this person has to live another 40 years and this continues to go down, they're going to potentially be staring down the barrel of needing dialysis the last five years of their life." Y- again, you don't want ... You want to die with compromised kidney function, but never from compromised kidney function. In fact, the hazard ratio of all 'cause mortality associated with compromised kidney function is even greater than that of heart disease. Once, once you cross that threshold, I mean, lights out. Once you are needing dialysis, I mean, your risk of death is higher than that of someone with high blood pressure, smoking, even someone who has cancer. You have a higher risk of death having end stage renal disease than you do having cancer. So, um, the kidney is so sensitive to blood pressure. This is a tiny organ that on every pump of your heart is getting 20 to 25% of your blood.
Episode duration: 3:29:55
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