Exercise, Nutrition, Hormones for Vitality & Longevity | Dr. Peter Attia

1. 0:00 – 2:51

   Assessing Health Status & Improving Vitality

   1. AHAndrew Huberman0:00

      (uptempo 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. Dr. Attia is a physician who's focused on nutritional, supplementation-based, behavioral, prescription drug, and other interventions that promote healthspan and lifespan. His expertise spans from exercise physiology to sleep physiology, emotional and mental health, and pharmacology. Today, we talk about all those areas of health, starting with the very basics, such as how to evaluate one's own health status and how to define one's health trajectory. We also talk about the various sorts of interventions that one can take in order to optimize vitality while also extending longevity, that is, lifespan. Dr. Attia is uniquely qualified to focus on the complete depth and breadth of topics that we cover, and indeed, these are the same topics that he works with his patients on in his clinic every day. Dr. Attia earned his Bachelor of Science in mechanical engineering and applied mathematics and his MD from Stanford University School of Medicine. He then went on to train at Johns Hopkins Hospital in general surgery, one of the premier hospitals in the world, where he was the recipient of several prestigious awards, including Resident of the Year. He's been an author on comprehensive reviews of general surgery. He spent two years at the National Institutes of Health as a surgical oncology fellow at the National Cancer Institute, where his work focused on immune-based therapies for melanoma. In the fields of science and medicine, it is well-understood that we are much the product of our mentors and the mentoring we receive. Dr. Attia has trained with some of the best and most innovative lipidologists, endocrinologists, gynecologists, sleep physiologists, and longevity scientists in the United States and Canada. So, the expertise that funnels through him and that he shares with us today is really harnessed from the best of the best and his extensive training and expertise. By the end of today's episode, you will have answers to important basic questions such as, should you have blood work? How often should you do blood work? What specific things should you be looking for on that blood work that are either counterintuitive or not often discussed and yet that immediately and in the long term influence your lifespan and healthspan? We talk about hormone health and hormone therapies for both men and women. We talk about drug therapies that can influence the mind as well as the body. And of course, we talk about supplementation, nutrition, exercise, and predictors of lifespan and healthspan. It is an episode rich with information. For some of you, you may want to get out a pen and paper in order to take notes. For others of you that learn better simply by listening, I just want to remind you that we have timestamped all this information so that you can go back to the specific topics most of

2. 2:51 – 3:46

   Momentous Supplements

   1. AHAndrew Huberman2:51

      interest to you. I'm pleased to announce that the Huberman Lab Podcast is now partnered with Momentous supplements. We partnered with Momentous for several important reasons. First of all, they ship internationally because e- we know that many of you are located outside of the United States. Second of all, and perhaps most important, the quality of their supplements is second to none, both in terms of purity and precision of the amounts of the ingredients. Third, we've really emphasized supplements that are single ingredient supplements and that are supplied in dosages that allow you to build a supplementation protocol that's optimized for cost, that's optimized for effectiveness, and that you can add things and remove things from your protocol in a way that's really systematic and scientific. If you'd like to see the supplements that we partner with Momentous on, you can go to livemomentous.com/huberman. There, you'll see those supplements and just keep in mind that we are constantly expanding the library of supplements available through Momentous on a regular basis. Again, that's livemomentous.com/huberman.

3. 3:46 – 7:29

   Thesis, InsideTracker, Helix Sleep

   1. AHAndrew Huberman3:46

      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 Thesis. Thesis makes custom nootropics that are designed for your unique needs. And to be honest, I'm not a fan of the word nootropics because nootropics means smart drugs, and to be honest, there is no such thing as a smart drug because there's no neural circuit for being smart. There are neural circuits rather for being creative or for task switching or for focus. And as we all know, different sorts of demands, whether or not they are cognitive or physical, require different types of cognitive and physical abilities. Thesis understands this and has created a kit of custom nootropics that are tailored to your needs. To get your own personalized nootropic starter kit, you can go to takethesis.com/huberman, take their three-minute quiz, and Thesis will send you four different formulas to try in your first month. That's takethesis.com/huberman and use the code Huberman at checkout to get 10% off your first box of custom nootropics. Today's episode is also brought to us by 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 many of the factors that impact your immediate and long-term health can only be assessed from a quality blood test. And nowadays, with the advent of modern DNA tests, you can also analyze, for instance, what your biological age is and compare it to your chronological age, and obviously it's your biological age that really matters.The challenge with a lot of blood tests and DNA tests, however, is that you get information back about metabolic factors, hormones, and so forth, but you don't know what to do with that information. InsideTracker makes it very easy to know what to do with that information to optimize your health. They have a personalized platform, it's a dashboard that you go to. You can click on the level of any hormone, metabolic factor, lipid, et cetera, and it will tell you the various sorts of interventions based on nutrition, supplementation, et cetera, that you can use to bring those numbers into the ranges that are ideal for you. If you'd like to try InsideTracker, you can visit insidetracker.com/huberman to get 20% off any of InsideTracker's plans. That's insidetracker.com/huberman to get 20% off. Today's episode is also brought to us by Helix Sleep. Helix Sleep makes mattresses and pillows that are of the absolute highest quality. They also have some really unique features because they are customized to your unique sleep needs. I've talked over and over again on this podcast and on other podcasts about the fact that sleep is the foundation of mental health, physical health, and performance. There's just simply no other substitute for a quality night's sleep on a regular basis. I've been sleeping on a Helix mattress for well over a year now, and it's the best sleep that I've ever had, and that's in large part because the mattress was designed for me. What you need to know, however, is what's the ideal mattress for you? And you can do that by going to Helix site. You can take their brief quiz, which will ask you, "Do you sleep on your side, your back, your stomach, or maybe you don't know, or maybe all three. Do you tend to run hot or cold in the night? Maybe you know, maybe you don't." At the end of that short quiz they will match you to the ideal mattress for you. I matched to the Dusk, the D-U-S-K, mattress, but again, that's what I need, that's not necessarily what you need in order to get your best night's sleep. But if you're interested in upgrading your mattress, go to helixsleep.com/huberman, take their two-minute sleep quiz, and they'll match you to a customized mattress for you, and you'll get up to $200 off any mattress order and two free pillows. They have terrific pillows. And you get to try out that mattress for 100 nights risk-free. They'll even pick it up for you if you don't love it, but I'm certain you will. Again, if you're interested, you can go to helixsleep.com/huberman for up to $200 off your mattress order and two free pillows. And now for my discussion with Dr. Peter Attia.

4. 7:29 – 11:51

   Lifespan: Bloodwork & Biomarkers Testing, The “4 Horseman of Disease”

   1. AHAndrew Huberman7:29

      Peter, thanks for joining me today.

   2. PAPeter Attia7:31

      Thanks for having me, man.

   3. AHAndrew Huberman7:32

      I've been looking forward to this for a very long time.

   4. PAPeter Attia7:34

      Oh, that's nice.

   5. AHAndrew Huberman7:35

      I'm a huge fan of your podcast. I know that you went to Stanford and worked with a number of people that are colleagues of mine, so for me, this is already a thrill just to- just to be doing this.

   6. PAPeter Attia7:45

      Yeah, well, it's- likewise.

   7. AHAndrew Huberman7:47

      I have a ton of questions, uh, but I want to start off with something that I wonder a lot about and that I know many other people wonder about, which is how to assess their current health and their trajectory in terms of health and well-being, specifically as it relates to blood work. So what are your thoughts on blood work? Is it necessary for the typical person? So this is somebody who's not dealing with some acute syndrome or illness. And at what age would you suggest people start getting blood work? How frequently should they get blood work? How often do you get blood work done, et cetera.

   8. PAPeter Attia8:21

      Yeah, there's a lot there. I mean, the way I talk about this with patients is first taking everything back to the objective. So what- what- what's the- what's the- what's the thing we're trying to optimize? So if- if a person says, "Look, I'm- I'm trying to break ten hours for an Ironman," I don't know that blood work is going to be a game-changing aspect of their trajectory and their training. You know, they're gonna benef- benefit much more from sort of functional analyses of performance. So I'm assuming, based on the question, that you're really coming at this through the lens of living longer and living better through the lifespan/healthspan-

   9. AHAndrew Huberman8:57

      Mostly.

   10. PAPeter Attia8:58

       ... lens.

   11. AHAndrew Huberman8:58

       Yeah. And just, I think most people have some sense of their vitality or lack of vitality, but I think everyone wonders whether or not they could feel better and whether or not blood work will give them a window into how they might go about feeling better.

   12. PAPeter Attia9:11

       Yeah, I think it does to some extent, but I also think that it has a lot of blind spots. So I kind of, you know, break things down into the two vectors that make up longevity, which are lifespan and healthspan. So lifespan is the easiest of those vectors to understand because it's- it's- it's pretty binary, right? You're alive or you're not alive, you're respiring or you're not, you make ATP or you don't. End of story. So, um, what gets in the way of lifespan is essentially the four horsemen of disease, right? So atherosclerotic disease, cancer, neurodegenerative disease, and metabolic disease, which directly isn't the cause of many deaths, but you know, bec- basically creates the foundation to all of those other diseases. Um, so, you know, if you're a non-smoker, what I just rattled off is about 80% of your death. So how does blood work help address those? It varies. So on the atherosclerotic standpoint, it's a very good predictor of risk if you know what to look for. Uh, so primarily ApoB would be the single most important, um, lipoprotein that we care about. I can explain what that means in a second. Um, and then also, you know, other markers of inflammation, endothelial health, um, and metabolic health. When it comes to cancer, you know, blood testing in the sense of biomarkers is not particularly helpful outside of knowing that the second leading environmental or modifiable cause of cancer is metabolic ill health after smoking. So we don't actually know a lot about cancer in the sense of what causes it. Uh, it's- it's really stochastic and it's a lot of bad luck. So we know that smoking drives it and we know that even though epi- epidemiologically we say obesity drives it, what- what it really means is metabolic poor health. It's probably the hyperinsulinemia that comes with obesity that drives it. So biomarkers help with that, but there's still an enormous blind spot to cancer. We could talk about liquid biopsies aside 'cause those aren't really biomarker studies, but put that away. On the neurodegenerative side, you know, I don't think we have a lot of insight that comes to understanding Parkinson's disease, but when it comes to dementia, particularly Alzheimer's disease, which is the most prevalent form of dementia, I think the biomarkers can be quite helpful. They overlap a lot with the atherosclerotic diseases. So the same things that, you know, drive the risk of heart disease are drawing- dri- driving the risk of dementia.Um, and then there's some novel stuff as well. If you include genetic testing, which you can get out of a, a blood test, we get a whole suite of genes, not just ApoE, but far more, you know, nuanced stuff than that, that can also play a role. So you can stratify risk in that sense. So in aggregate I would say, you know, blood testing and biomarkers provides pretty good insight into lifespan.

5. 11:51 – 13:59

   Healthspan: Functional Testing, Cognitive & Emotional States

   1. PAPeter Attia11:51

      When you get into health span, you have kind of the cognitive, physical, emotional domains. I think here the, the biomarkers are far less helpful, and here we kind of rely more on functional testing. So when it comes to sort of the cognitive piece, uh, you know, you can do cognitive testing. In terms of long-term risk, a lot of the things that imply good cognitive health as you age, um, are in line with the same things that you would do to reduce the risk of dementia. So all the biomarkers that you would look to improve through dementia risk reduction, you would be improving through cognitive health. On the physical side, I mean, outside of looking at hormone levels and things which we look at extensively, and understanding how those might, um, aid in or prevent some of the metrics that matter, it really is, th- this is a biomarker aside thing. I mean, I'd be much more interested in a person's DEXA, CPET testing, VO2 max testing, you know, zone two lactate testing, fat oxidation, those what I would consider more functional tests that give me far more insight into that. And then of course the emotional piece, which depending on, you know, who you are, might be the single most important piece, without which none of this other stuff matters, right? If you're a totally miserable human being, your relationships suck, I don't think any of this other stuff matters. (laughs) Uh, and certainly there's nothing that I'm looking at in biomarkers that's giving me great insight into that.

   2. AHAndrew Huberman13:10

      Do you ask about emotional state, or do you try and assess emotional state indirectly when you do an intake with one of your patients?

   3. PAPeter Attia13:17

      Um, probably not so much in the intake because I think it takes a while to form a relationship with a patient before that starts to become something that they're necessarily going to want to talk with you about, but I definitely think of it as an important part of what we do, and I think without it, none of this other stuff really matters. A- again, the irony o- of thinking about how many years I spent sort of in pursuit of fully optimizing every detail of everything without any attention being paid to that dimension, is not lost on me. And, and look, there are some patients who they, that's just not something that, that's something that's compartmentalized. Maybe they're, you know, they're doing well in that department, or maybe they aren't, but they just aren't willing to engage on that yet.

   4. AHAndrew Huberman13:58

      In terms

6. 13:59 – 16:01

   Blood Testing: Best Frequency

   1. AHAndrew Huberman13:59

      of frequency of blood testing, uh, if somebody feels pretty good, um, and is taking a number of steps, exercise, nutrition, et cetera, to try and extend lifespan and improve health span, um, is once a year frequent enough? Um, and should a 20-year-old start getting blood work done just to get a window into what's going on? Assuming that they can afford it or their insurance can cover it.

   2. PAPeter Attia14:24

      Yeah, I mean look, I, I, I certainly think everybody should be screened early in life because if you look at, like what's the single most prevalent genetic driver of atherosclerosis is LP little A. So unfortunately most physicians don't know what LP little A is and yet, you know, somewhere between 8% and 12% of the population has a high enough, and depending on who you, you know... Uh, I had a recent guest on my podcast who suggested it could be as high as 20% have a high enough LP little A that it is contributing to atherosclerosis. So to not want to know that when it's genetically determined, right? This is something that, you know, you're, you're born with this and you only need to really check it once. Why we wouldn't want to know that in a 20-year-old when it can contribute to a lot of the early atherosclerosis we see in people, uh, you know, it just, it's, you know, it's leaving money on the table in my opinion. The frequency with which you need to test really comes down to the state of interventions. You know, I, I don't think it makes sense to just do blood tests for the sake of doing blood tests. There has to be kind of a reason. Is something changing? Um, you know, a blood test is for the most part a static intervention. Uh, it's a, it's a, it's a, it's a look at a window in time, and there's benefit in having, you know, a few of those over the course of a year if you're unsure about a level. So if something comes back and it doesn't look great, yeah, it might make sense just to recheck it without reacting to it. But typically, you know, in patients we might check blood two to four times a year, but we're also probably doing things in there to, to now check like, "Hey, you know, we, we gave this drug, did it have the desired outcome?" Um, you know, "You put on three pounds of muscle and lost three pounds of fat. Did it have the desired outcome?"

   3. AHAndrew Huberman16:00

      Um,

7. 16:01 – 22:33

   DEXA Scan: Lean Mass & Fat, Bone Mineral Density & Osteoporosis

   1. AHAndrew Huberman16:01

      speaking of tracking weight and, um, fat/lean mass percentages, is that something that you recommend your patients do pretty often? I know people that step on the scale every day. I know people, like myself, that frankly I might step on the scale three times a year. I don't really care. I care, I pay attention to other things that are far more subjective. I, maybe I'm making a huge mistake. Wh- what are your thoughts about, um, quantitative measurements of weight, uh, BMI, uh, for the typical person?

   2. PAPeter Attia16:29

      I think they're pretty crude. Um, I think a DEXA, I, I'd rather take a DEXA annually, um, and then maybe follow weight a little bit more closely to get a sense of it. And so with a DEXA you're getting, at least the way we look at the data, four pieces of information. Now most people when they do a DEXA, w- should I explain what that is? I'm

   3. AHAndrew Huberman16:50

      Yeah, I think, uh, some people might not know what DEXA is. I, in fact, I confess I have a crude understanding of what it is. Um, my... Tell me if... where I'm wrong a- and, um, hopefully where I'm part, at least partially right. My understanding is that there are a number of different ways to measure lean mass to non-lean mass ratio, and they, there's one where they put you under water, there's one where they put you into some sort of non-underwater chamber, there's caliper-ing.

   4. PAPeter Attia17:14

      Yep.

   5. AHAndrew Huberman17:14

      And then there's the, um, looking in the mirror and, and, um, pinching and, and, uh, changing the lighting. (laughs)

   6. PAPeter Attia17:20

      (laughs) You know, it's funny, when, when, i- if you've, if you've done it enough you can, I can sort of tell my body fat by my abs, right? So I can sort of tell by, you know, how good the six-pack or how bad the six-pack is, what the leanness is. And that's, that's actually not a terrible, uh, way to do it. There are, you know, a bodybuilder for example, which I've never been, can, can tell you the difference between being 6%, 7%, 8%, 10%-

   7. AHAndrew Huberman17:41

      Wow.

   8. PAPeter Attia17:41

      ... just based on-...the degree of visibility within, within the abs. Um, but, uh, basically a DEXA scan is an x-ray. Um, so it's the same principle as, you know, just getting a chest x-ray, where ionizing radiation is passed through the body, and there's a plate behind the body that collects what comes through. And there, the denser the mid- medium that the electrons are trying to go through, uh, the less of them that are collected. So when you look at an x-ray, as everybody's probably seen an x-ray, that which is white is most dense. So if you had, you know, a piece of metal in your pocket, it would show up as a bright white thing. That's why ribs and bones show up as white. And the things that are the least dense, like the lungs where it's just air, are the blackest. And everything is a shade of gray in between. So a DEXA is just doing that effectively, but it's a moving x-ray. So you lay down on a bed and it takes maybe 10 minutes, and this little, very low power x-ray kind of goes over your body, and the plate beneath it is, is collecting information that is basically allowing it to differentiate between three things. Bone mineral content, fat, other. And the other is quantified as lean body mass. So that's organs, muscles, everything else. So when most people do a DEXA, the- the fir- you know, they get the report back and the reports are horrible. I've- I've yet to see one company that can do this in a way that isn't abjectly horrible. We- we've created our own templates, so we have our own dashboard for how we do this, 'cause we've just given up on trying to use theirs. But the first thing most people look at is, "What's my body fat?" And this is the gold standard outside of like MRI or something that's only used for research purposes. So, so a DEXA is going to produce a far better estimate of, of body fat than calipers or, uh, buoyancy testing or things like that, provided the machinery is well calibrated and the operator knows how to use it. Um, I've heard some people argue that in the hands of like the guy who's been doing calipers his whole life, it could probably be comparable with calipers. But nevertheless, for an off-the-shelf tech, you know, a DEXA's amazing. You know, of the four things that get spit out of the DEXA, we think that the body fat is the least interesting, and so I would rank that as fourth on the list of what's germane to your health. The other three things that you get spit out are bone mineral density, uh, visceral fat, and then the metrics that allow you to compute, uh, like to s- basically compute what's called appendicular lean mass index and fat-free mass index. And so those three metrics are significantly more important than body fat. And, um, the reason is as follows, right? So, so bone mineral density basically speaks to your risk of osteoporosis, um, and osteopenia. Um, and that doesn't sound very sexy to people our age. You know, 50-year-old guy is listening to this, it's like, "Yeah, big deal." But for a 50-year-old woman, this is a huge deal, right? A woman who's just about to go through menopause or has just gone through menopause is at an enormous risk for osteopenia and, and then ultimately osteoporosis because estrogen is the single most important hormone in regulating bone mineral density. Uh, and we can come back and talk about why that's the case, but it's, it's very interesting how the, how the biomechanics of, of, um, bones work and why estrogen specifically is so important. And this is a huge cause of morbidity, right? So, you know, if you're over the age of 65 and you fall and break your hip, your one-year morbidity is about 30% to 40%. Which again, just to put that in English, if you're 65 or older, you fall and break your hip, there's a 30% to 40% chance you're dead in a year.

   9. AHAndrew Huberman21:20

      Wow.

   10. PAPeter Attia21:21

       Bones matter. Um, so we want to really get a sense of where you stack up for your age, for your sex. And if you're anywhere off the pace, we have to ramp up our strategy and be super aggressive about how to increase that. Or at a minimum, prevent any further decay.

   11. AHAndrew Huberman21:41

       And are there age-related charts for these-

   12. PAPeter Attia21:43

       Yeah.

   13. AHAndrew Huberman21:43

       ... sorts of things?

   14. PAPeter Attia21:44

       Yeah, this is, this all gets spit out into what's called a Z-score. So when you're looking at your BMD, it's gonna give you a Z-score. So a Z-score of zero means, uh... And you, you understand this, but it's like, uh, it's z-score referring to a probability distribution in a standard mode. So Z-score of zero means you're at the 50th percentile for your age and sex. A Z-score of plus one, you're one standard deviation above, minus one below, et cetera. Um, there's also a T-score, which is doing the same thing but comparing you to a young person. And so the T-score is technically used to make the diagnosis of osteopenia or osteoporosis. We t- we tend to look more at the Z-score and basically say, "Look, if your Z-score right now is minus one, in four years, I want your Z-score to be zero." Not necessarily because you've increased that entire way, but maybe you've increased slightly while it's expected that you would've declined.

   15. AHAndrew Huberman22:31

       I see.

8. 22:33 – 29:24

   Bone Mineral Density & Age-Related Decline, Strength Training, Corticosteroids

   1. AHAndrew Huberman22:33

      W- what are some things that we can do to improve bone mineral density at any age?

   2. PAPeter Attia22:38

      So it turns out there's a real critical window in which we are malleable. So depending on the age at which someone's listening to us discuss this, um, you know, if you're, if you're under 20, 25, you are still in that time of your life when you are able to reach your potential. So, um, it turns out that strength training is probably the single best thing you can do. And this was a surprise to me, 'cause we, you know, we did an AMA on this topic a little while ago and that's when I got, you know, really deep on this with our analysts. My assumption was, oh, running must be the best. Like some sort of impact must be the best thing you can do. It was, you know, I assumed running would be better than swimming and cycling, but it turned out that power lifting was probably (laughs) the best thing you could do. Um, and I think once you understand how bones work, it became more clear, which is, you know, power lifting is really putting more of a sheer force from the muscle via the tendon onto the bone, and the, that's what the bones are really sensing. They're sensing that sheer force that's being applied through the bone in a, in a compressive way depending on the bone of course, and that's what's basically activating the osteoblasts, which are the cells that are, you know, a- a- allowing bone to be, uh, built. So...It's, this is, this turns out to be probably more important for females, um, because how high you can get during that period of development, say till you're 20 or 25, basically sets your trajectory for the rest of your life. So where we get into real trouble is with patients who, for example, used large amounts of inha- inhaled steroids during that period of their life, 'cause let's say they had really bad asthma, or patients who needed large amounts of corticosteroids for some other immune-related condition. So during their critical window of development they were taking a drug that was impairing this process. So, you know, we have some patients like that in our practice and that's, you know, just an enormous liability that we're working really hard to overcome, you know, with nutrition, with hormones, with drugs, with training, um, and, you know, it's, it, you know, it's just something you have to be aware of.

   3. AHAndrew Huberman24:41

      I wasn't aware that, um, inhalants, uh, for asthma and things of that sort can impair bone mineral density. Um-

   4. PAPeter Attia24:48

      Yeah, if they're steroid-based. Er, I mean some of them, of course, are just beta-agonists and they're fine.

   5. AHAndrew Huberman24:52

      So anything corticosterone-like?

   6. PAPeter Attia24:54

      Yep.

   7. AHAndrew Huberman24:55

      Interesting. Uh, and then I always get asked this question and I n- I always reflexively want to say no but I don't k- really know the answer so I don't reply. What about topical, um, corticosterone? You know, people will put cortisone cream. To me it seems almost inconceivable that it would have a systemic effect, but then again, what do I know?

   8. PAPeter Attia25:11

      It's all, it's all dose and, it's all dose and, and time-related. So, you know, if you're talking about like, "I've got a little rash under my skin, I'm gonna put, you know, corticosteroids on," probably not.

   9. AHAndrew Huberman25:20

      Mm-hmm.

   10. PAPeter Attia25:20

       Um, but, but certainly with enough of it put on, I mean it is absorbed, so, um, it, it could be an issue. But that's not typically what we're concerned with. I mean we're mostly concerned with people that are, you know, taking even modest amounts of prednisone for months, years at a time, um, or, like I said, kids that are using steroid inhalers for years and years and years. Again, I'm not suggesting that if your kid's on a steroid inhaler they shouldn't be. You have to solve the most important problem, and if asthma is the most important problem, so be it. I think you just want to turn that into, okay, well how much more imperative is it that our kid is doing things that are putting a high amount of stress on their bones and, via their muscles, to make sure that they're in that maximal capacity to build?

   11. AHAndrew Huberman26:05

       Do you think that somebody in their 30s or 40s or 50s could still benefit from strength training in terms of bone mineral density and longevity, um, as it relates to bone mineral density, uh, given that there's this k- key window earlier they might have missed that window?

   12. PAPeter Attia26:19

       Oh, yeah, no, no, this is essential for the rest of life because you're now trying to prevent the falloff. So, so basically the way it works is you, you're sort of, from, from birth to, say, 20, you're in, you're in growth. From 20 to 50 you plateau. At 50 men start to decline but it's really small, women start to decline, and it's precipitous.

   13. AHAndrew Huberman26:36

       And it's related to the drop in estrogen associated-

   14. PAPeter Attia26:39

       Yep. Yep.

   15. AHAndrew Huberman26:39

       ... with menopause or pre-menopause?

   16. PAPeter Attia26:40

       Correct.

   17. AHAndrew Huberman26:41

       And, and can we get into any of the broad, uh, contours of, of what that strength training looks like? We had An- Dr. Andy Galpin on the show, he talked a lot about ways to build strength versus hypertrophy versus endurance, et cetera. I think there's pretty good agreement across the fields of, you know, physiotherapy, et cetera, of physiology and, and medicine, in terms of how to do that. But my understanding is fairly low repetition ranges, so this is anywhere from one to six repetitions, typically not aiming for, you know, a pump, hypertrophy, that sort of thing, but heavy loads that are hard to move, ei- 80% of one repetition maximum or more, done with long rest periods, um, three, two to, you know, three times a week type thing? Is that about right?

   18. PAPeter Attia27:24

       Yeah, if you, if you look at the literature on this, it's gonna tell you, it's gonna differentiate power lifting from weightlifting. In other words, yeah, you do need to be kind of moving against a very heavy load. Now again, that can look very different depending on your level of experience. Like, I really like deadlifting. Now, I mean, I can count the number of days left in my life when I'm gonna want to do sets over 400 pounds, but, you know, I'll pick and choose the days that I do. But, but, you know, I grew up doing those things, I'm comfortable with those movements. If I had a 60-year-old woman who's never lifted weights in her life who we now have to get lifting, I mean, we could get her to deadlift, but I, I, I think I wouldn't make, you know, perfect the enemy of good. I'd be happy to put her on a leg press machine and just get her doing that.

   19. AHAndrew Huberman28:11

       Mm-hmm.

   20. PAPeter Attia28:13

       Um, you know, it's not as pure a movement as a deadlift but who cares, right? We can still put her at a heavy load, for her, and do so safely. So, um, now that said, I mean, there was a study that was done in Australia, uh, and I'm, you know, hopefully we can find a, a link to it, it's, there's a video on YouTube that actually kind of has the PI sort of walking through the results.

   21. AHAndrew Huberman28:31

       Nice.

   22. PAPeter Attia28:31

       I could send it to you after.

   23. AHAndrew Huberman28:32

       Okay, yeah, we'll track it down.

   24. PAPeter Attia28:33

       And it's, it's just amazing. Y- they took a group of, you know, older women, they looked like they were in their 60s or 70s, who had never lifted weights in their life, who, you know, had osteopenia and some probably already had osteoporosis, and they basically just put them on a strength training protocol. And it is remarkable to watch these women. They're doing good mornings, they're doing deadlifts, they're picking heavy things up off the ground. I think one woman was picking up, god I want to say she was like picking like 50, 60 kilos up off the ground. I mean just staggering sums of weight for these women who have never done anything. And their bone health is improving at this age. So, um, the goal frankly is to just, you know, never get to the point where, you, you know, you have to do this for the first time. Uh, you know strength training is such an essential part of our existence that, um, you know, there's nev- you're n- it's never too late to start but you should never stop.

9. 29:24 – 31:03

   Osteopenia & Osteoporosis Diagnosis, Strength Training

   1. PAPeter Attia29:24

   2. AHAndrew Huberman29:24

      Love that advice. Is it a systemic effect or a local effect? So for instance, um, let's say that, well, my mother is in her late 70s, um, she actually used to be really strong. When we were kids she could move this fish tank that was in my room long before I could move it, and, um, I was always like, "She's really strong." Over the years, um, I would, I wouldn't call her frail by any means, but I certainly think she could benefit from some strength training. Let's say she were to start doing some leg presses or start even with air squats and maybe work up to some push-ups.... or the effect's all local, meaning if she were to just train her legs or just do push-ups, um, would it only be the loads applied to the, uh, limbs and, and muscles and tissues-

   3. PAPeter Attia30:04

      I think that's-

   4. AHAndrew Huberman30:05

      ... that were involved?

   5. PAPeter Attia30:05

      ... I think that's where the bulk of it is, yeah.

   6. AHAndrew Huberman30:06

      Okay.

   7. PAPeter Attia30:06

      Yeah. S- s-

   8. AHAndrew Huberman30:07

      So you need to train the whole body, essentially.

   9. PAPeter Attia30:09

      Yeah. Now, keep in mind, the diagnosis of osteopenia and osteoporosis is based on only three locations, the left hip, the right hip, and the lumbar spine. So, um, y- y- you know, that's just the convention by which we make the diagnosis. And, and I think part of that has to do with that's where the majority of the insults occur. Now, not all of the insults. I've seen people that have, you know, because of horrible bone density, they're, they're, you know, they're fracturing ankles and tibia, fibula, like they're having low tib-fib fractures just walking. Um, so clearly bone density outside of those regions does matter, but, uh, much of it is really focused on... And by the way, you know, you fall, you break a wrist. So, so this is a systemic issue, um, but the majority of the response is a local response-

   10. AHAndrew Huberman30:54

       Mm-hmm.

   11. PAPeter Attia30:54

       ... 'cause it really comes down to putting a load directly on that bone and then having that bone, in kind, respond by laying down more bone.

10. 31:03 – 32:16

    AG1 (Athletic Greens)

    1. PAPeter Attia31:03

    2. AHAndrew Huberman31:03

       Before we continue with today's discussion, I'd like to just briefly acknowledge our sponsor, Athletic Greens, now called AG1. Athletic Greens, AKA AG1, is an all-in-one vitamin mineral probiotic drink that also has adaptogens and digestive enzymes. I've been taking Athletic Greens since way back in 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens, and the reason I still drink Athletic Greens twice a day, is that it supplies total foundational coverage of my vitamin mineral needs and it supplies important nutrients that I need to support my gut microbiome. The gut microbiome, as many of you know, supports the immune system. It also supports the so-called gut-brain axis, which is vital for mood, for energy levels, for regulating focus, and many other features of our mental health and physical health that impact our daily performance and high performance in any endeavors we might be involved in. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and claim a special offer. They're giving away five free travel packs, plus a year's supply of vitamin D3 K2 with every order. And of course, vitamin D3 K2 are vital for all sorts of things like hormone health and metabolic health, and K2 for cardiovascular health and calcium regulation. Again, you can go to athleticgreens.com/huberman to claim that special offer.

11. 32:16 – 38:31

    Back-casting: Defining Your “Marginal Decade”

    1. AHAndrew Huberman32:16

       You mentioned falling and the problems with falling and breaking things and mortality related to that. I, I wonder whether or not there are also, um, health-related effects of just having weak bones that are not just about falling and breaking a bone and, and dying a year later, even th- though that's obviously very severe. Um, because I think when people hear about that, some people might think, "Well, I'll just be more careful."

    2. PAPeter Attia32:37

       (laughs)

    3. AHAndrew Huberman32:37

       "I'll just move more slowly. I'll sit in a wheelchair if I need to, if, um, even though I might be able to walk a bit, it keeps me from falling." Some people, I think, adopt that mentality. What are some of the benefits of having, um, high bone mineral density for men and women that are perhaps independent of risk of injury?

    4. PAPeter Attia32:55

       Well, I think it's actually the inverse of what you just said, right? It's sort of like you, you have to sort of be able to articulate what it is you want in your marginal decade. So we, we use this thing in our practice called the marginal decade. Marginal decade is the last decade of your life. So everyone will have a marginal decade. That's the only thing I can tell you with absolute certainty, right?

    5. AHAndrew Huberman33:16

       I believe you. (laughs)

    6. PAPeter Attia33:17

       There's no immortality. There's no hidden elixir that's gonna help us live to be, you know, whatever. I mean, we're all gonna be in our last decade at some point. Um, and outside of people who die suddenly or through an accident, um, most of us know when we're in that marginal decade. You might not know the day you enter it, but most people, you know, who are old enough, if you tell them, "Are you in the last decade of your life?" they probably have a sense that they are. So I think the exercise that we like to go through with our patients very early on is have them, in exquisite detail, more detail than they've ever considered, so we have to prompt them with like 50 questions, um, lay out what their marginal decade should look like.

    7. AHAndrew Huberman34:00

       Wow. That's a serious exercise.

    8. PAPeter Attia34:02

       It's a very serious exercise, right? Like what, tell me everything that is going to happen in your marginal decade. I don't know when it's gonna be, Andrew. It could be '87 to '97 if we're doing well, right? It might be '79 to '89. I don't know. But I, I, you know, it would really be an, uh, a very nuanced exploration of that topic. And I think until you do that, all of this other stuff is just abstract and kind of nonsense. You know, until a person can tell you what it is that they want to be doing in that last decade, you can't design a program to get them there. I mean, think about it, you know, someone wants to do an Ironman, we take it for granted that we know what the objective is. I have to be able to swim two and a half miles. I have to be able to get out, take my wetsuit off, hop on my bike, ride 112 miles, get off my bike, take the bike shoes off, put the run shoes on, run 26.2 miles. Like, we get it. We know what the objective is. And only by knowing that can you train. Can you imagine if I said to you, "Andrew, I'm going to have you do an athletic event in a year. Start training. I'm not gonna tell you what it is."

    9. AHAndrew Huberman35:06

       Right.

    10. PAPeter Attia35:07

        "Uh, just do it."

    11. AHAndrew Huberman35:08

        Right.

    12. PAPeter Attia35:08

        It could be playing basketball. (laughs) You know, it could be swimming to Catalina Island. It could be running a hundred miles. You wouldn't be able to do it. So similarly, if we don't know what our marginal decade is meant to be, I, y- there's no way to train for it.

    13. AHAndrew Huberman35:22

        Do you think this is a good exercise for anyone and everyone to do on their own, regardless of age? Here I'm hearing this-

    14. PAPeter Attia35:27

        Absolutely.

    15. AHAndrew Huberman35:27

        ... and I'm thinking, "I need to think about w- when my last decade might be and what I want that to look like."

    16. PAPeter Attia35:33

        Absolutely. I mean, when I say we do it with our patients, that's only because that's the population I work with, but there's simply no reason everybody shouldn't be going through this exercise.

    17. AHAndrew Huberman35:40

        And then you, you sort of back script from there-

    18. PAPeter Attia35:43

        Yeah, w- we, yeah, w-

    19. AHAndrew Huberman35:43

        ... figure out what people should be doing-

    20. PAPeter Attia35:44

        That's exactly-

    21. AHAndrew Huberman35:44

        ... given their current health status.

    22. PAPeter Attia35:45

        That's exactly right. We call it backcasting. So the first step we do is once we've really delineated what the objective function looks like, we then say, "Okay, how do you break down that into, uh, metrics that we can measure?"So, you know, you describe doing a whole bunch of things. Okay, just to let you know, to do that will require a VO2 max of 30 milliliters of oxygen per minute per kilogram. And the person will say, "Okay, what does that mean?" We'll say, "Well, that's a measure of your maximal uptake of oxygen and that declines at about 8% to 10% per decade." So if you have to be at 30, and let's just assume you're going to be doing that at 90, so what do you need to be at 80, 70, 60, 50? Okay, here's what it would need to be at 50. Okay, what are you now? Ah, there's a big gap. You're below where you need to be now. So you're obviously higher than 30 now, but if you're only at 42 now and you need to be at 30 in 40 years, you're not going to cut it. You have to be a lot fitter. Okay, now let's do the same exercise around strength and stability. And without exception, most people when they do this exercise will find out they're well below where they need to be. So the gravity of aging is more vicious than people realize, and therefore the height of your glider needs to be much higher than you think it is when you're our age if you want to be able to do the things we probably want to be able to do when we're 90.

    23. AHAndrew Huberman37:15

        I absolutely love this approach. I've never done it in terms of my health. I've always thought about what I want to accomplish in the next three to six months or next year or so.

    24. PAPeter Attia37:22

        And by the way, that's a great approach. That's forecasting. Forecasting is fantastic. Forecasting is really good at short-term things. It doesn't work for long-term things. Long-term, you have to do backcasting.

    25. AHAndrew Huberman37:33

        W- this backcasting approach really appeals to me because in my career, while I never antici- oops, excuse me. I never anticipated I'd be podcasting. Um, but that, that's what I did at some point as an undergraduate. I looked professors, I'm like, "That looks like a pretty good life. They seem pretty happy." I talked to a few of them and then I figured out what I need to do at each stage in order to get to that next rung on the ladder, and just kind of figured it out in, uh, in a backcasting kind of way, as you refer to it. Uh, I think this is incredibly useful because it puts all the questions about blood work and how often to get blood work and what to measure in t- in a really nice context that's highly individualized. I've never heard of this before, so, um...

    26. PAPeter Attia38:11

        And I should give a nod to Annie Duke. I used to always refer to this as reverse engineering. But in Annie Duke's book, she wrote about this exact s- thing and called it backcasting and I was like, "I like the term backcasting better." It, I think it's more intuitive than reverse engineering.

    27. AHAndrew Huberman38:24

        Mm-hmm. Yeah, there's a real genius to it and I think it, 'cause it sets so many things into the appropriate bins and trajectories. I've heard

12. 38:31 – 44:43

    All-Cause Mortality: Smoking, Strength, VO2 max

    1. AHAndrew Huberman38:31

       you talk before about some of the prime movers for longevity and all risk mortality. Um, and I'd love for you to review a little bit of that for us. Um, I think we all know that we shouldn't smoke because it's very likely that we'll die earlier if we smoke nicotine. Uh, I'm neither a marijuana nor a nicotine smoker, so I feel on stable ground there, but anytime we see smoking nowadays, people want, really want to distinguish between cannabis and nicotine. Um, so I am curious about any differences there in terms of, um, impact on longevity. But in that context, what are the things that anyone and everyone can do, should do, to b- to live longer, basically?

    2. PAPeter Attia39:13

       How long you got?

    3. AHAndrew Huberman39:15

       Uh, well you tell me.

    4. PAPeter Attia39:17

       (laughs)

    5. AHAndrew Huberman39:18

       (laughs) You tell me. (laughs) Um, I'd like to live to be... I'd like my final decade to be between 90 and 100.

    6. PAPeter Attia39:23

       Oh, no, I meant how long-

    7. AHAndrew Huberman39:24

       (laughs) No, no, I'm just kidding.

    8. PAPeter Attia39:25

       ... do you think-

    9. AHAndrew Huberman39:25

       I'm just kidding. I'm just kidding.

    10. PAPeter Attia39:25

        And will we spend from now until you're 90 talking about this?

    11. AHAndrew Huberman39:28

        Ah, y- well, there's a risk of that.

    12. PAPeter Attia39:29

        Yeah.

    13. AHAndrew Huberman39:29

        But, um, top contour is fine. I know you've done a lot of content on this.

    14. PAPeter Attia39:32

        Yeah, yeah.

    15. AHAndrew Huberman39:32

        And we'll, we will give people links to some of that more in-depth content. But, you know-

    16. PAPeter Attia39:37

        S- so, so-

    17. AHAndrew Huberman39:37

        ... let's say we were on a short flight from here to San Diego. Uh, we're in Los Angeles now.

    18. PAPeter Attia39:41

        Very well, very well.

    19. AHAndrew Huberman39:41

        Um, and we got takeoff and landing, and we don't want to kink our neck too much by doing this thing. So if I just said, "Hey, you know, give me the, the th- the extended version of the three by five card." Uh...

    20. PAPeter Attia39:52

        Yeah.

    21. AHAndrew Huberman39:52

        ... what does that look like?

    22. PAPeter Attia39:53

        Um, s- so let's start with a couple of the things that you've already highlighted. So smoking, how much does smoking increase your risk of all cause mortality? And, and the reason we like to talk about what's called ACM or all cause mortality is it's really agnostic to how you die. And that doesn't always make sense. I mean, if you're talking about, you know, a s- a very specific intervention like a anti-cancer therapeutic, you really care about cancer-specific mortality or heart-specific mortality. But when we talk about these sort of broad things, we like to talk about ACM. So, you know, using smoking, smoking is approximately a 40% increase in the risk of ACM.

    23. AHAndrew Huberman40:29

        And what does that translate to in, um, that means I'm, w- I'm shortening my life by 40%?

    24. PAPeter Attia40:35

        No. It means at any point in time, there's a 40% great- greater risk that you're going to die relative to a non-smoker than an ever smoker.

    25. AHAndrew Huberman40:42

        Got it. Got it.

    26. PAPeter Attia40:42

        Yeah, yeah. So it's important to distinguish. It doesn't mean your lifespan is going to be 40% less. It means at any point in time standing there, your risk of death is 40% higher. Um, and by the way, that'll catch up with you, right? At some point that, that catches up. Um, high blood pressure. It's about a 20 to 25% increase in all cause mortality. Um, you take something really extreme like end stage kidney disease. So these are patients that are on dialysis waiting for a- a- an organ. And again, there's a confounder there because there's, what's the underlying condition that leads you to that? It's, you know, profound hypertension, you know, significant type two diabetes that's been uncontrolled. You know, that's enormous. That's about 175% increase in ACM. So the hazard ratio is like 2.75.

    27. AHAndrew Huberman41:25

        Mm-hmm.

    28. PAPeter Attia41:26

        Um, type two diabetes is probably about a 1.25 as well. So a 25% increase. So now the question is like, how do you improve? So what are the things that improve those? So now here we do this by comparing low to high achievers on other metrics. So if you look at low muscle mass versus high muscle mass, what is the improvement? And it's pretty significant. It's about three X. So if you compare low muscle mass people to high muscle mass people as they age, the low muscle mass people have about a three X hazard ratio or 200% increase in all cause mortality. Now, if you look at the data more carefully, you realize that it's probably less the muscle mass fully-... doing that and it's more the high association with strength. And when you start to s- tease out strength, you can realize that strength could be probably three and a half X as a hazard ratio, meaning about 250% greater risk if you have low strength to high strength.

    29. AHAndrew Huberman42:26

        And high strength is the ability to move loads at 80% to 90% of one rep-

    30. PAPeter Attia42:30

        So it's all defined, it's, uh, it's all defined by given studies. So some, the most common things that are used are actually, you know, they're used for the purposes of experiments that make it easy to do, and I don't even think they're the best metrics. So they're usually using like grip strength, um, leg extensions, and like wall sits, squats, things like that.
13. 44:43 – 49:24

    Attia’s Rule of Supplementation, “Centenarian Decathlete” Physical Goals

    1. AHAndrew Huberman44:43

       eh, so maybe we could talk a little bit about the specifics around the training to get into the, um, you know, top two tiers there, because it seems that those are enormous positive effects of cardiovascular exercise. Uh, far greater than the sorts of numbers that I see around, let's just say supplement A or supplement B.

    2. PAPeter Attia44:59

       Well, and, and, and, and that's, you know, like this is my whole pet peeve in life, right? It's like I just can't get enough of the machinating and arguing about this supplement versus that supplement, and I feel like you shouldn't be having those arguments until you have your exercise house in order.

    3. AHAndrew Huberman45:17

       Mm-hmm.

    4. PAPeter Attia45:17

       Um, you know, you shouldn't be arguing about your, this nuance of your carnivore diet versus this nuance of your paleo diet versus this nuance of your vegan diet, like, until you can deadlift your body weight for 10 reps. Like then, then you can come and talk about those things or something.

    5. AHAndrew Huberman45:33

       Right.

    6. PAPeter Attia45:33

       Like, let's just start with some metrics.

    7. AHAndrew Huberman45:35

       Yep.

    8. PAPeter Attia45:35

       Like, until your VO2 max is at least at the 75th percentile and you're able to dead hang for at least a minute and you're able to wall sit for at least two, like we could rattle off a bunch of relatively low hanging fruit. I wish there was a rule that said, like, you couldn't talk about anything else health related. Like, you just-

    9. AHAndrew Huberman45:52

       W- we can make that rule. I mean-

    10. PAPeter Attia45:53

        (laughs) No one will listen to it.

    11. AHAndrew Huberman45:54

        I don't know about that. We can make whatever rules we want.

    12. PAPeter Attia45:56

        (laughs)

    13. AHAndrew Huberman45:56

        We can call Attia's Rule.

    14. PAPeter Attia45:58

        (laughs)

    15. AHAndrew Huberman45:58

        And one thing I've done before on this podcast and on social media is just borrowing from the tradition in science which is, it's inappropriate to name something after yourself unless you were a scientist before 1950.

    16. PAPeter Attia46:08

        (laughs)

    17. AHAndrew Huberman46:08

        Um, but it's totally appropriate to name things after other people, so I'm going to call it Attia's Rule.

    18. PAPeter Attia46:12

        (laughs)

    19. AHAndrew Huberman46:12

        Until you can do the following things, um, don't talk about supplements.

    20. PAPeter Attia46:15

        Please refrain from talking about supplements and nutrition.

    21. AHAndrew Huberman46:18

        There it is.

    22. PAPeter Attia46:18

        Yeah, there you go.

    23. AHAndrew Huberman46:18

        Hereafter, thought of, referred to-

    24. PAPeter Attia46:21

        (laughs)

    25. AHAndrew Huberman46:21

        ... and referenced as Attia's Rule. I coined the phrase, not him-

    26. PAPeter Attia46:24

        (laughs)

    27. AHAndrew Huberman46:24

        ... so there's no ego involved, but it is now Attia's Rule. Watch out, #AttiasRule.

    28. PAPeter Attia46:30

        Oh, God.

    29. AHAndrew Huberman46:30

        Um, Wikipedia entry, Attia's Rule. In all seriousness, and I am serious about that, um, dead hang for about a minute seems like a, a really good goal for a lot of people, at least th-

    30. PAPeter Attia46:40

        That's our, that's our goal. I think we have a minute and a half is the goal for a 40-year-old woman. Two minutes is the goal for a 40-year-old man. So we adjust them up and down based on, uh, age and gender.
14. 49:24 – 55:23

    Importance of Exercise, Brain Health, MET hours

    1. AHAndrew Huberman49:24

       in mice, um, or brain atrophy or brain, uh, hypertrophy, et cetera, (laughs) um, in animal models, it's very clear that the best way to get a nervous system to atrophy, to lose neurons, shrink neurons and/or lose connections between neurons is to stop that animal from moving-

    2. PAPeter Attia49:41

       Yep.

    3. AHAndrew Huberman49:42

       ... or to de-enrich its environment, depriv- deprive it of some sensory input or multiple sensory inputs. And the best way to enhance, um, the size of neurons, the number of connections between neurons, and maybe even the number of neurons is to enrich its environment and get it moving while enriching that environment.

    4. PAPeter Attia49:56

       Uh, uh, you know, Andrew, I think it's, it's very difficult for me to say that the same is not true in humans. And, and so the first time this became clear to me was in 2014. Um, I had an analyst, Dan Pelachar, and I said, "Dan, I'm gonna give you a project that is vexing me to no end, which is, um, I want you to look at all of the literature that we have, both mechanistic and clinical trial data, that talks about Alzheimer's prevention. And I want to know every single type of input, and I wanna have a, a clear sense of via what mechanism does it offer what mode of protection." And it took Dan... And this was obviously we, we iterated a lot on this together. Um, and he came back with kind of an amazing presentation that took alm- I don't know, nine months to a year of work. And what amazed me was (laughs) when he came back to it, he said, "The single greatest efficacy we can point to is exercise." And I was like, "Dan, that's gotta be nonsense, dude. There's no way exercise is the single best thing you can do for the brain. There has to be some drug you've missed. There has to be some other thing that you've missed." And he's like, "No, like this is hands down the best thing, 'cause you're... You know, it's not just what it's doing to BDNF, it's not just what it's doing to vascular endothelium, it's not just what it's doing to glucose disposal and insulin signaling and all these things. Like it's just touching every aspect of the brain." And I was very skeptical for about six months, kind of really pushed on him and I was like, "I, I think you're missing something, Dan. I think you're missing something." And then finally in the end looped in Richard Isaacson, who's a neurologist that we work with really closely on Alzheimer's prevention, and, you know, ultimately it turned into a paper that we wrote (laughs) basically on, you know, about this, about this, this topic and, and, and, and a few others 'cause again I thought, "Oh, are you sure it's not EPA and DHA? Like, that's gotta have a bigger impact." And, um, again, there's a lot of things that I think do matter and there's a whole host of things that we do for Alzheimer's prevention, but I think you're absolutely right. There's not one thing that I'll tell patients is more important than exercising. And by the way, it's not the sort of pathetic recommendations that are made. Like it- it's you have to exercise a lot more if you want to get this maximum benefit. You will, you will get... You know, the maximum benefit comes going from nothing to something. So if you go from being completely sedentary to doing 15 MET hours per week, you'll get probably a 50% reduction in risk.

    5. AHAndrew Huberman52:22

       Wow.

    6. PAPeter Attia52:22

       Uh, so a MET hour... A MET, just for people who don't know, is a metabolic equivalent. So it's we're, we're exerting about 1.3 METS sitting here talking. If we were sitting here being quiet, it would be about one MET. Um, you know, walking really briskly would be about five METS. So 15 MET hours per week would be three one-hour really brisk walks. That's not a lot of work. But just going from doing nothing to doing that would give you 50% of the benefit that you would get from going all the way. Now I, again, I think... I'm personally a little skeptical of how much that's... I think it's probably a bit less than that. I think there's more upside than people appreciate, but the studies I don't think can, can truly capture that. But look, you know, there's, there's no reason to not be exercising more than that and, and capture more benefit even though the rate at which you accrue it is less, and it also speaks to the health span side of this, which is not necessarily captured in those data. The health span gets back to the functional piece we opened with, which is what do you want to be doing in your marginal decade? Do you want to be able to pick up a great grandkid if they come running at you? Do you want to be able to get up off the floor... Do you want to be able to play on the floor with a kid and then get up on your own? Not be pulled-

    7. AHAndrew Huberman53:33

       Yeah, and I think most people are thinking at final, uh, years of life they're trying to think, you know, how can they, um, take themselves to the bathroom. They're thinking how can they sit up off the toilet.

    8. PAPeter Attia53:42

       Yep.

    9. AHAndrew Huberman53:43

       I mean, they are really bas- vegetative-type functions, right? (laughs) Um, at some level. Uh, I love this, again, this idea of marginal decade and using that as a way to backcast to, uh, uh, to actual methods and behaviors and, um, protocols that one should be doing on a daily basis. Uh, I'll use ANIC data as it's now called, um, to cite just... I know three Nobel Prize winners, which doesn't mean anything except that they did beautiful work, but the point is that they're all in their 90s. So I'll, I'll, I'll name them 'cause I'm, I'm complimenting them for what they've done, not just their work but what I'm about to describe. So Eric Kandel at Columbia-... Noble prize-winning for work on memory. Torsten Wiesel, work on neuroplasticity, and then, uh, Richard Axel, who's also at Columbia, Nobel Prize-winning work for molecular biology of smelling and, um, microbiology generally. All three of them, still alive, Richard's younger compared to the other two, all three of them either swim, jog, or play tennis, or racquetball I think is Richard's thing, multiple times per week.

    10. PAPeter Attia54:45

        Mm-hmm.

    11. AHAndrew Huberman54:45

        Eric was sw- they're all cognitively still extremely sharp, still interested in the arts, doing science, curious about science, running laboratories, writing books, going on podcasts. I mean, it's incredible. Again, that's anecdata, but I was kind of surprised to learn that colleagues that were so intellectually strong were also so obsessed with exercise. I mean, they, they really are obsessed with their exercise routine, and earl- early on linked that to their, um, some of their intellectual vigor over time. I w- wanted to just also use that as a jumping off point to ask about one kind of niche thing, but it comes up, um, I don't think I'm going to out which one of those told me this, but one of those three individuals, um, chews an excessive

15. 55:23 – 1:03:12

    Nicotine & Cognitive Focus

    1. AHAndrew Huberman55:23

       amount of Nicorette.

    2. PAPeter Attia55:24

       Mm-hmm.

    3. AHAndrew Huberman55:25

       Used to be a smoker and I asked him why, and he said because, in his estimation, it's protective against Parkinson's and Alzheimer's, or at least the nicotinic acetylcholine augmentation of nicotine, 'cause nicotine is an acetylcholine receptor obviously, um, is known to create a state of focus and, and neural enhancement. What are your thoughts about not smoking, let's just-

    4. PAPeter Attia55:50

       Yeah.

    5. AHAndrew Huberman55:50

       ... I just want to be really clear. People, don't smoke nicotine, vape nicotine, it's going to shorten your life. Just terrible idea, addictive, et cetera, in my opinion. But what are your thoughts about augmenting acetylcholine through the use of nicotine in order to keep the brain healthy and focused? Again, this is one Nobel Prize winner, so it's, uh, truly n of one, but he's so convinced that this matches up with the mechanistic data on acetylcholine and cognition, that I'd love to get your thoughts on it.

    6. PAPeter Attia56:16

       So I can't speak to the AD prevention component of it, uh, I'd have to run that by a couple of my colleagues who I collaborate with on that, but I can definitely speak to the cognitive enhancement piece of it, and I actually did an AMA on this, uh, probably a year ago, where I went into all of the gory details of it, and talked about my own use of, of nicotine, which I'll cycle on and off. I've been doing it for the last 10 years. I haven't-

    7. AHAndrew Huberman56:40

       What form do you take it in?

    8. PAPeter Attia56:41

       Uh, I used to use the gum, I don't like the gum anymore, so now I like these little lozenges, um, that, uh, and I'll tell (laughs) you a funny story about this. So our mutual acquaintance, David Sinclair, mentioned a compy- company to me a year ago. He's like, "Hey, have you heard of this company?" And I forget the name of the company, but he gave me some name. So I go online, and it's like this company selling nicotine. And I'm like, "I wonder why he's asking me to do this? Well, I'll, I'll just order a bunch, and then we'll figure out why." 'Cause we were, you know, there was some reason we were doing this potentially through investment. So I get a, like literally order like a lifetime supply of this stuff, and it's pretty good. It's actually, it's a really nice little patch, 'cause I, the thing I didn't like about the gum was I hated just the, the, the taste of it. Um, so then the next week I'm talking to David, and I'm like, "By the way, I ordered all that nicotine stuff you told me about." He's like, "What?" And he goes, "Oh, oh, the company's name was something else. It was totally unrelated." (laughs)

    9. AHAndrew Huberman57:41

       (laughs)

    10. PAPeter Attia57:41

        I was like, "Oh, God." Um, so, um, the short answer is, I think this stuff is absolutely a concentration, um, enhancing substance. Um, it is addictive, and people need to be wary of that. Now, it's not addictive to everybody. I personally experience no, um, addiction to it whatsoever. So I can, I could do it every day for 30 days and stop, and experience no withdrawal. I could forget about it. It doesn't really seem to matter. Um, you have to be careful with the dose, truthfully. I mean, remember, one cigarette is about one milligram of nicotine, and a lot of these lozenges will plow four to eight milligrams into you in one shot, and for someone who is, you know, naive to that, like I am, four milligrams is a lot of nicotine in one bolus.

    11. AHAndrew Huberman58:31

        Mm-hmm.

    12. PAPeter Attia58:31

        So you just have to be very mindful of it. Um, I got a lot of flack when I did this AMA, for obvious reasons, but people were like, "How can you, as a doctor, encourage people to use nicotine?" And I was like, "First of all, I'm not encouraging anybody to use it, I just want to be able to talk about the biochemistry of it." Um, and if disclosing that I use it from time to time is, is an endorsement, then, you know, I apologize for that. Um, but on the list of things that you can do to make your brain a little more focused, I would consider this infinitely safer than what a lot of people are doing, which is using stimulants.

    13. AHAndrew Huberman59:05

        Mm-hmm.

    14. PAPeter Attia59:06

        I mean, to me, I, I, I, you know, I just help patients outright, like, we are under no circumstance prescribing stimulants. I mean, it doesn't-

    15. AHAndrew Huberman59:14

        Interesting.

    16. PAPeter Attia59:14

        Yeah. We're just, we're not giving anybody Adderall. We're not giving anybody Vyvanse or any of these things. Um, not to say they don't have an inappropriate clinical use, but they should be prescribed under the care of somebody who's really monitoring the use case for it, and, and, and, and using that as a tool to enhance, you know, concentration and cognitive performance is not something we're comfortable doing.

    17. AHAndrew Huberman59:33

        Yeah, it's rampant on college campuses.

    18. PAPeter Attia59:36

        I, I can only imagine.

    19. AHAndrew Huberman59:37

        Um, armodafinil, modafinil, which are slightly different of course, but, uh, so non-clinical use, not prescribed for ADHD, but just it's rampant. Recreational use, study-based use. Um-

    20. PAPeter Attia59:48

        But the data I've seen on modafinil suggests that it only really provides a nootropic benefit in someone who is deprived of sleep. Is there data that in a totally well-rested person there is a nootropic benefit of modafinil?

    21. AHAndrew Huberman1:00:01

        I don't know. I have one experience with armodafinil, where I took a half a recommended dose. This was prescribed by a doctor. Um, I went to give a talk. This was in Hawaii. And, um, four hours into the talk, uh, my, uh, co-speaker came up to me and just said, "Well, first of all, you got a little bit of, uh, spit in the corner of your mouth, and second of all, you haven't blinked in three minutes, and third, um, there's only two people left in the audience." (laughs) I was so lasered in, uh...... that I kind of forgot the context. (laughs) Um, and I'm a little bit of a, kind of a tunnel vision OCD type-

    22. PAPeter Attia1:00:31

        (laughs)

    23. AHAndrew Huberman1:00:31

        ... uh, anyway, but one, that was all it took. I never, I never took any more of it. It was a powerful stimulant.

    24. PAPeter Attia1:00:36

        Mm-hmm.

    25. AHAndrew Huberman1:00:37

        I take, uh, 300 milligrams of Alpha-GPC now and again, before some cognitive work, sometimes before workouts, and I do subjectively feel that it narrows my focus in a, in a nice way. Um, but I don't take it more than once or twice a day, and more than once or twice a week. ?

    26. PAPeter Attia1:00:53

        So this is an example of where, you know how we were talking about exercise versus sort of nutrition and supplements for longevity, I think there may be a whole bunch of things that are kind of interesting around focus, but nothing would compare to changing our environment. Like, I think that if I compare my focus today to my focus when I was in college, there's no comparison. Like in college, I was truly a robot, but I think a large part of it was there was no distraction. There was no email.

    27. AHAndrew Huberman1:01:20

        Right.

    28. PAPeter Attia1:01:20

        There was no social media.

    29. AHAndrew Huberman1:01:21

        Right.

    30. PAPeter Attia1:01:21

        There was no internet. I mean, I was in college when Mosaic launched in the early '90s, like I, you know, and you had to walk like a mile to get to the computer lab on a big Sun Workstation to do anything in, you know, some computer code language. So y- when you're sitting in your room studying, there was no distraction, and I think that's a far greater component of what it means to be focused than the challenges we have today. So, you know, my thoughts on this would be, if we really wanted to return to a state of focus, we're gonna have to individually do something about, you know, our environment, and it, and I don't, I don't know what the answer is. Like, I've tried every little trick I can think of, like closing my browsers when I'm writing and stuff, but, you know, I'm just not strong enough willed. Like I'll pick up my phone every 20 minutes to look and see if I missed a text message or something stupid.
16. 1:03:12 – 1:10:10

    Menstruation, PMS & Menopause

    1. AHAndrew Huberman1:03:12

       Uh, when Robert Sapolsky came on the podcast, we talked a little bit about menopause and the data around menopause. He's very interested in, um, these findings that, I think I'm going to get this right, that whether or not women benefit from estrogen therapy to offset menopause really depends on when that therapy is initiated. I don't know if you're aware of those data, but, uh, he claimed that if they begin estrogen therapy in the middle to tail end of menopause, the outcomes can be, um, quite bad, whereas if they initiate those estrogen therapies as they enter menopause or even before menopause, then the outcomes can be quite good. I don't know what percentage of the patients you treat are male versus female, and what ages those patients are of course, but, um, what are your thoughts about estrogen therapy for women, menopause, and, um-

    2. PAPeter Attia1:04:00

       Oh.

    3. AHAndrew Huberman1:04:00

       ... hormone therapies generally for women? Maybe even testosterone therapy, you hear about that these days.

    4. PAPeter Attia1:04:04

       Yes.

    5. AHAndrew Huberman1:04:04

       And then we'll talk about men.

    6. PAPeter Attia1:04:05

       So, so our practice is probably 70/30 male/female, so we have lots of women, and this is a very important topic. Um, it's also probably... Let me think. I just want to make sure I'm not being hyperbolic when I say this. Yep, I don't think I am. It's hands down the biggest screw-up of the entire medical field in the last 25 years.

    7. AHAndrew Huberman1:04:30

       Uh-

    8. PAPeter Attia1:04:30

       Now again, it's possible in the next hour I'll think of, nope, there's a bigger screw-up. But I don't-

    9. AHAndrew Huberman1:04:34

       Another, another giant screw-up.

    10. PAPeter Attia1:04:35

        Yeah. But, but I don't think I will. I, I'm pretty confident that I won't be able to think of a bigger act of incompetence than what happened with the Women's Health Initiative in the late '90s and early 2000s, which is effectively the study that turned the entire medical field off hormone replacement therapy for women. So, it's important, I think, to explain what the study looked at. So this was a, a study that was conducted in response to the widely held belief in the '70s and '80s that women should be placed on hormones as they're, uh, going through menopause, right? Menopause is... I guess maybe I'll even take a step back. I don't know how much your audience is familiar with how estrogen/progesterone work. Is it worth going into that stuff?

    11. AHAndrew Huberman1:05:26

        Yeah, probably worth mentioning a bit of the top contour.

    12. PAPeter Attia1:05:29

        Yeah.

    13. AHAndrew Huberman1:05:29

        Uh, some of them might be familiar with it. We've done episodes on estrogen and testosterone, but frankly, as I think back to those, we didn't really go into the biology of estrogen and testosterone enough.

    14. PAPeter Attia1:05:38

        Yeah, so, I mean, (laughs) actually an interesting aside that I always tell my female patients, who get a kick out of this, um, when you look at a woman's labs, you'll see her estrogen, her progesterone, her FSH, her LH, her testosterone, her sex hormone-binding globulin, all these things, but based on the units they're reported in, it's a very distorting picture of what the most common androgen is in her body. If you actually convert them to the same units, she has much more testosterone in her body than estrogen.

    15. AHAndrew Huberman1:06:07

        Interesting.

    16. PAPeter Attia1:06:07

        Yeah.

    17. AHAndrew Huberman1:06:08

        I did not know that.

    18. PAPeter Attia1:06:09

        Yeah.

    19. AHAndrew Huberman1:06:10

        Then again, I've never been a woman getting my hormone profile done.

    20. PAPeter Attia1:06:12

        Yeah, yeah. So even though a woman's testosterone is much less than a man, uh, than a, than a man's level, um, it's still more than she has estrogen in her body.

    21. AHAndrew Huberman1:06:21

        Wow.

    22. PAPeter Attia1:06:21

        So phenotypically, right, estrogen is the hormone that's dominating, and tes- so it's the, you know, she has much higher estrogen than a man and much lower testosterone than a man, but in absolute amounts, she has more testosterone than estrogen. Just worth pointing that out.

    23. AHAndrew Huberman1:06:34

        Incredible.

    24. PAPeter Attia1:06:35

        So, um...So, so, you know, what, what's happening to a woman from the age she starts menstruating till she goes through menopause, i- outside of pregnancy and birth control and stuff like that, is she has this cycle. You know, roughly every 28 days, but it can vary, where, uh, at the beginning of her period, we call that day zero, her basic ... her estrogen and progesterone are very low. You can't measure them. And then what happens is the, uh, estrogen level starts to rise, and it rises in response to a hormone called follicle stimulating hormalone- uh, follicle stimulating hormone, FSH, that is getting her ready to ovulate. And she ovulates at about the midpoint of her cycle. So if we're just going to make the math easy, on day 14 she's going to release a follicle from one of her ovaries. And the estrogen level is sort of rising, rising, rising. We love to measure hormones on day five, because I want to have a standardized way in which I measure her hormones. So our women know, if we're in the business of trying to understand her hormones, the day her period starts, even if it's just a day of spotting, that becomes our benchmark, and then day five, I want to see every hormone on that day. And if everything is going well, I know what her FSH, LH, estradiol, and progesterone should be on that day. So the estrogen rises, starts to come down a little bit as she ovulates, and then the luteinizing hormone kicks on, because it's now going to prepare her, uh, uterus for, uh, the lining to, uh, uh, accommodate a pregnancy. So now you start to see estradiol go back, but now for the first time progesterone goes up. So progesterone has been doing nothing for 14 days, and now it starts to rise. And actually progesterone is the hormone that's dominating the second half, which is called her fol- fol- uh, her luteal cycle. So the first 14 days is the follicular cycle, second is the lute- luteal cycle. So once you get to about the halfway point of that, which is now, just to do the math, 21 days in, the body has figured out if she's pregnant or not. And again, most of the time she's not going to be pregnant, so the body says, "Oh, I don't need this lining that I've been preparing. I'm going to shed it." So now progesterone and estrogen start crashing, and the lining is what is being shed, and that is the menses. By the way, it's that last seven days of that cycle that, in a susceptible woman, is what creates those PMS symptoms. So it's the ... And actually, this is something that you would probably have a better understanding of than me. There is something about this in a susceptible woman, where the enormous reduction of progesterone so quickly is probably impacting something in her brain.

    25. AHAndrew Huberman1:09:01

        Mm-hmm.

    26. PAPeter Attia1:09:01

        So I think this is a, this is a legitimate thing, right? I mean, uh, you know, it's not like, oh, she's crazy because she's having all these PMS symptoms. No. Um, we know that that's the case because if you put women on progesterone for those seven days, those symptoms go away.

    27. AHAndrew Huberman1:09:14

        Interesting.

    28. PAPeter Attia1:09:14

        So if you can stabilize their progesterone during the last half-

    29. AHAndrew Huberman1:09:17

        Mm-hmm.

    30. PAPeter Attia1:09:18

        ... of their luteal phase, and sometimes we would just do it for the entire luteal phase, just put them on a low dose of progesterone, all PMS symptoms vanish.
17. 1:10:10 – 1:22:06

    Hormone Replacement Therapy, Menopause & Breast Cancer Risk

    1. PAPeter Attia1:10:10

       goes down. Why don't we just give her estrogen? 'Cause that's clearly going to help with some of the symptoms of menopause. So what, what do women experience when they go through menopause? The first symptoms are what are called vasomotor symptoms. So this is usually in the form of, um, night sweats, hot flashes. Uh, so ... A- and depending on the woman, this can be really significant, right? These are women who can have a hard time sleeping. They can be having hot flashes during the middle of the day. They can wake up soaked in a pool of sweat. Um, those tend to pass after a couple of years, and then they get into sort of the more long-term complications of menopause. So what we call vaginal atrophy, vaginal dryness, and then the stuff that we talked about a while ago, which is the, uh, osteopenia, osteoporosis. Uh, a lot of women will compa- complain of brain fog. Um, so I mean, clearly this was an issue, and it was recognized 70 years ago. Why don't we give women estrogen back to replace that hormone? And so that went on for a couple of decades, maybe less, maybe a decade. And then it was realized, wait a minute, we were driving up the risk of uterine cancer. Um, and the reason for that is if you just give estrogen with no progesterone to antagonize it, you will thicken the endometrium endlessly, and you will increase the risk of hyperplasia. Well, you'll u- you'll definitely undergo hyperplasia, and then ultimately dysplasia. Dysplasia is pre-cancerous, and ultimately, uh, we were seeing that. So people figured out, well, actually if you want to give estrogen to a woman who still has her uterus, you have to give her progesterone as well. You have to be able to have a hormone to oppose the estrogen. And then that became effectively, in the 19 ... call it the 1970s-ish, the standard for, um, for HRT. So in the early 1990s, uh, the NIH said, "Look, we haven't really studied this." You know, we have a ton of epidemiology that says giving women hormones seems to be doing really good things. They feel better, so their, all their symptoms go away. Uh, they seem to have lower risk of heart disease, lower risk of, you know, uh, cardiovascular dis- uh, pardon me, lower risk of cardiovascular disease, lower risk of, uh, bone fractures. Um, everything seems to get better. Lower risk of diabetes. But we haven't tested this in a randomized prospective trial, so let's do this. So that became the WHI. And it randomized ... It had two parallel arms, so it had a group for women who did not have a uterus-Uh, so these are women that had undergone hysterectomy for some other reason, and then it had a group for women that did have their uterus. In the first group, the, there was a placebo arm and then an estrogen-only arm, and in the other group, there was a progesterone plus estrogen versus a placebo. Everything about the way this study was done is a bit wonky. Some of it is justifiable, but it's important to understand. First, the women were all way outside of menopause. So, none of these women were started when you would normally start HRT, and, um, there were probably, uh, several reasons for that, but one of them is, and I think this is a, a legitimate reason, they wanted hard outcomes. They wanted to know death rates. And if you're doing this on women in their 50s, you just weren't gonna get it, right? You couldn't-

    2. AHAndrew Huberman1:13:36

       You have to wait too long.

Episode duration: 2:50:02