Peter’s takeaways on bone health, calorie restriction, addiction, & gene editing (PS 3 sneak peek)

1. 0:00 – 0:09

   Intro

   1. PAPeter Attia0:00

      [upbeat music] Hey, everyone. Welcome to "The Drive" podcast. I'm your host, Peter Attia.

2. 0:09 – 2:50

   Overview of topics to be covered

   1. SPSpeaker0:10

      Peter, welcome to another quarterly podcast summary AMA, which is a mouthful. How you doing?

   2. PAPeter Attia0:17

      Good. Do we have an abbreviation for that?

   3. SPSpeaker0:19

      I think it's QPS one, two, three. This is three.

   4. PAPeter Attia0:24

      QPS three AMA 60 something.

   5. SPSpeaker0:28

      Well, yeah.

   6. PAPeter Attia0:29

      All right.

   7. SPSpeaker0:29

      Yeah, we're just gonna keep throwing numbers at it until it sticks.

   8. PAPeter Attia0:32

      All right. Perfect.

   9. SPSpeaker0:32

      'Cause that's definitely not confusing to the listener.

   10. PAPeter Attia0:35

       Well, thank you for coming to Austin to do this one in person.

   11. SPSpeaker0:38

       Yeah, it's honestly weird to not look at you through a screen for one of these.

   12. PAPeter Attia0:43

       I feel the same way.

   13. SPSpeaker0:44

       Yeah, I can't hide what I usually do behind the screen in this one.

   14. PAPeter Attia0:47

       [laughs]

   15. SPSpeaker0:47

       So this is a much more serious episode. So for this one, as a reminder for people, because it's still relatively new, um, what we're doing with these quarterly podcast summaries is we're taking previous episodes and just kinda going through them with your thoughts. And this came about because you take an insane amount of notes through the podcast. You have them in front of you there. And so we would internally kinda go through these, and we did a few of these, and people really liked them. And so what we're gonna do is we'll go through... We won't necessarily summarize them as much as you will talk about your big takeaways, and then we'll kind of have a conversation on how that's affected either your behavior, how you deal with patients, anything of that nature. And so for today's episode, we're gonna talk about dopamine through Anna's podcast. We have CRISPR, which is super interesting through Feng's podcast, bone mineral density, lifting in females, especially as you age with Belinda, calorie restriction with Eric, which is always of interest, and then prostate cancer, which was kind of a special shorter episode we did with Ted. So I think it's really good, kind of a huge variety of things that we'll cover. But with that said, anything you wanna say before we roll?

   16. PAPeter Attia2:02

       No, just to reiterate, I mean, I don't-- I, you know, I'm sure I'll have said this already in the intro, um, which I obviously haven't recorded yet, that this is not a substitute for going back and listening to the podcast because I'm not even attempting to provide the full context of everything. What I'm really trying to do is capture what I'm taking away in real time as I'm having these discussions with people. What, what am I making notes on? So that's, that's effectively the filter here is what, what is Peter pulling out of this as the most interesting stuff? Um, and, and sometimes that comes with an assumption that other content is understood and heard. So the hope is that you're listening to this after you've heard these podcasts, or that you listen to these and maybe go back and listen to a podcast that you skipped because the insight is particularly interesting.

   17. SPSpeaker2:49

       Yeah, definitely.

3. 2:50 – 14:46

   Anna Lembke episode: addiction, dopamine's role in pleasure and pain, and managing addictive behaviors

   1. SPSpeaker2:50

      Let's start with Anna's episode, which covered dopamine. She has a great book, super interesting episode. So do you wanna kinda start with what your main takeaways were from that episode?

   2. PAPeter Attia3:02

      Yeah. So I, I read, um, Anna Lembke's book obviously before interviewing her. Um, enjoyed it a lot and, you know, was kind of looking forward to talking about this and, and, and had a, had a lot of questions about, you know, what, what really constitutes addiction. Um, and, and... 'cause I think the book is really about addiction more than it is about dopamine, right? Dopamine is kind of a heuristic. Everybody's heard the term dopamine. Everybody understands what dopamine is. It's a neurotransmitter. It's one of the most important neurotransmitters in the reward system and therefore in, in the addiction system, but it's by far-- it's not the only one. Um, and so I think my interest was maybe even personally a little bit less in the nuts and bolts of dopamine and more around the, the science of addiction. Um, so, so you know, we started with kind of defining the, the traditional aspects of, of, of, um, of what in-- uh, what defines addiction, so the sort of out of control compulsive use, the cravings, the continued use despite consequences, uh, and then the tolerance, uh, to, to the stimulus, and then ultimately withdrawal when it's removed. So again, if you view that through the traditional lens of how people think of an addiction like alcohol, all of those things clearly check, check, check, check, check. Um, but of course, there are behavioral things that show up here as well, everything from gambling to sex to workaholism. Uh, many of these things can constitute an addiction. Um, now one of the things I took away from this that I found interesting was the idea of what are the, what are the factors that influence this? Uh, in particular, I wanted to really understand how heritable addiction was, meaning how much is this written into the genetic code? Uh, it turned out quite a bit according to the heritability data. Now again, you'll often hear us talk about these. This came up even in the podcast with, with Carl Desroche where we talked about, um, eating disorders, depression, uh, schizophrenia. So the, the typ- the typical way that these c- uh, conjoint twin studies are done is they look at the prevalence of a certain condition in identical twins that were raised apart. That's really the best tool we have to understand how much of a role do genes play. You take two people with identical genes raised in a completely different environment. And based on that, um, Anna said that addiction is about fifty to sixty percent heritable. That's a huge amount, obviously. But, you know, it's a big enough amount that it can't be ignored, but it's not so big an amount that the die is cast, meaning just because you come from a, a line of people who have an addiction to one thing or another doesn't mean that your fate is sealed. So what are the other two things, um, that play a role in this? And, um, she described them as nature and neighborhood. So nature, nurture, neighborhood. Sorry, I might have misspoke that, right? Nature, genes, nurture, how you're raised, and neighborhood, meaning the environment you're in. Now, she wasn't able to provide, or at least if she was, I missed it, um, what the percent is for, uh, nurture versus neighborhood. But again, if heritability is 50 to 60%, we're gonna say 40 to 50% comes from how you were raised, and I don't just mean, like, the obvious things, but I also mean the subtle things, right? So were you raised around people that are engaging in a certain behavior? Do you experience-- Do you have experiences in life, for example, trauma, that might predispose you to certain addictive behaviors? This idea of neighborhood is very important, and I, I think it, it really has a lot to do with anybody who's ever considered trying to break a bad habit. So if you're, if you struggle with gambling, um, it's really hard to break a gambling habit if all your friends are gamblers. You either have to get a bunch of new friends or somehow just decide you're gonna hang out with a bunch of people who gamble but not do it yourself. Very difficult. Um, another topic that I, I just found incredibly fascinating, and I don't think we know the answer as the takeaway is, why do some people have a certain lock and key configuration for certain addictions, right? So why is it-- I use myself as an example, I think, in the podcast. I really enjoy alcohol. Like, it's not like I'm repulsed by the taste of alcohol. I quite enjoy it, like literally enjoy the taste. I, I just don't think I could be an alcoholic if I tried. In other words, if you surrounded me with alcoholics, it still-- it would never appear to me, uh, appeal to me to drink in the morning or to, to drink in a manner that, that would y- you know, lead to excessive use. So why is that? It's clearly not moral superiority. That's not what I'm trying to say. It's that there is something in my brain that doesn't get enough of that cycle from alcohol, that it doesn't, it just doesn't work for me that way. The same is true with gambling. Like, you know, I was in Vegas, remember giving a talk a little while ago, had to walk through a casino like twenty-five times to and from where I was going. A- and again, I don't say this to be disparaging of the people that are in casinos at seven in the morning, but, like, I, I just couldn't imagine. Like, if you said to me, "Peter, we have a job for you. You just have to sit in the casino and play blackjack, and we'll pay f- we'll pay you a million dollars a month to do this and cover all your winnings and your-- cover all, cover all your losses, and you can keep all the winnings." Like, I couldn't do it. Like, I couldn't imagine something less appealing. Um, and yet there are obviously people who can ruin their lives doing this. Why? And by the way, there are things that I'm addicted to that most people would look at and say, "That is awf-- Like, who could do that?" This why question I don't think we have an answer to yet. Um, and yet it totally fascinates me. Like, to me, that's the, that, that's the most interesting question in this, in this space. How does Anna work with clients? She's a psychiatrist, and one of the first steps that she, um, thinks about, and I think this is valuable for any of us that are trying to cope with our own addictions, is she does a four-week dopamine fast, which means a four-week total abstinence from the behavior that one is trying to rid themselves of. Um, she said that eighty percent of her clients, her patients, will feel better after the four-week fast. Now, she also noted some of those people need medications to help them through that. So, for example, if a person is trying to do a dopamine fast around alcohol, they may actually require benzodiazepines medically to help with that transition. Of course, that's not always the case. She also talked, I think, and I can't remember if this was in her book or we talked about it, uh, but I think we also discussed it, was, uh, a woman that was basically smoking pot twenty-four/seven, uh, and was doing it because of her anxiety. But of course, turned out she was having all the anxiety because she was smoking all the pot, but this wasn't realized until she was able to sort of abstain from it. Okay, another thing that I found just a very, uh, interesting, um, sort of nuance was around plain-- pain and pleasure. So, um, one of the examples we used was that of cold plunging. So people have heard me talk a lot about cold plunging. I'm a huge fan of it, although I still firmly maintain it has no longevity benefit. There's no geroprotective benefit of cold plunging. Um, so, you know, to all the biohackers out there, I'm s- I'm sorry, but I don't think this is gonna make you live longer. But I do think there are two distinct benefits. I think one is a, a reduction in inflammation and muscle soreness, and I think the other, for select people, is an improvement in mood. Now, Anna talked about how she's tried cold plunging many times and has never experienced an improvement in mood. And I was like, "Oh, that's super interesting." Um, I've heard many people say that, but I've heard just as many people share my experience, which is no matter what mood I'm in, no matter how foul it is, if I get into a forty-degree bathtub, bury myself to my neck for ten minutes, I feel insanely good after that. And again, it's not unlike the issue we discussed earlier of why do some people have the key go in the lock for alcohol and it's like both thumbs up, and then other one, other people don't have it. So what it really comes down to is endogenous dopamine production from pain. So Anna talked about how we live in a state of homeostasis, right? This is obviously a factor, uh, spread across all of biology. So when it comes to maintaining regular glucose levels, when it comes to maintaining a regular pH, body temperature, all of the core things that allow us to live require homeostasis, and the body has remarkable tools for adjusting up and down to keep us in that window, and dopamine is no exception. And so when we do something that is difficult, that induces pain, and the two examples that she gave were cold immersion and exercise The body has to offset that pain somehow, and it does so by increasing the endogenous production of dopamine. And what's different about this is, one, it's not a huge rush of dopamine that you get for free. It's this dopamine that you kind of had to work for to offset something you're doing that's actually causing pain. So when you remove the pain- painful stimulus, i.e., when you get out of the cold plunge or when you stop the workout, you have this lingering effect of that heightened dopamine. But again, it's a physiologic level, and it hasn't been sort of a hijacked level. Um, there was a line in Anna's book that, um, [lips smack] she credits to the person who said it, and I can't remember who that was, but I loved it, right? Which is, like, our brains are like cactuses that now reside in rainforests, right? So we evolved in an environment where stimulation was relatively modest, and our brains had normal tools for kind of coping with the up and down swings of dopamine. Um, and now we live in the most stimulating environment imaginable, and obviously, we just didn't have enough time to adapt. You know, anybody, you know, can, can sort of follow the logic there. Um, and so I think that makes a lot of sense, and it probably speaks to kind of what I think of as the, the big takeaways from this, right? So the big takeaways here, especially if you're a parent, is to sort of ask the question, like, what are we doing to prevent our kids' brains from being hijacked by this? So even the world you and I grew up in, I mean, I'm more than ten years older than you, but whether you grew up in the '70s or the '80s, like, we still grew up in a relatively stimulation-free world. I mean, the most stimulating thing in my life was a cheap cathode ray tube TV watching reruns of Happy Days. Like, that was the pinnacle of stimulation in my life. And today, forget about it. Like, it's y- you know, kids wouldn't even know what that is if they saw it. So everything is, is, is in Technicolor. Um, and, um, and two things she said really probably stand out. One is social media, the other is pornography. Again, I u- I think I brought up the example of when I was a kid, pornography was a Playboy magazine. Today, it's VR, literally, right? So, um, all of this stuff, there's just no way around it. Like, y- as a parent, I think you just have to be the one that's in charge of saying, like, "We're gonna absolutely minimize, avoid these things to the best of our ability." Um, she... You know, I don't think there's much I would add here because so much of this is advice I think everybody already kind of knows about when, you know, how much you limit smartphones, social media, all of those things. Um, [lips smack] yeah, I think those are the, those are the big takeaways from this podcast.

4. 14:46 – 22:08

   Follow-up questions about addiction: heritability, cold therapy, exercise, and strategies for breaking addictive behaviors

   1. SPSpeaker14:46

      So a few follow-up questions there. First is on the heritability piece, right? So about f- 50 to 60%, which is large. And I know we've talked in other podcasts about the importance of, like, family history and taking a detailed family history, typically as it relates to diseases, cardiovascular disease, Alzheimer's, things of that nature, cancer. Um, so when you're having patients and new patients do family histories, are you now having them also include kind of addictions in there? Have you always done that?

   2. PAPeter Attia15:16

      Yeah, it's a good question. So we don't have dedicated questions around it, but usually we-- I, I would say we almost always come up with it just through the detailed questioning around everything else. And the reason is, it's very difficult for a person to struggle with an addiction to alcohol or drugs and not have it creep into their health. So it's very common that we hear, you know, uh, you know, "Uncle Jimmy, you know, he, he died of, uh, you know, he died of heart disease when he was 60, but you know, truth be told, like, he had a real drinking problem, and da, da, da, da." So yeah, we usually emerge from the family history knowing full well, but I actually think it's a good point. I think we could be more deliberate about it. And, and I think we're in-- You know, we obviously pay just a lot of attention to this when it comes to, to mental health as well. Um, because, you know, when you, when you, when you go through the family history and you see a number of family members with mental illness, you just realize that there's a greater susceptibility as well.

   3. SPSpeaker16:13

      Yeah. And then let's talk a little bit more about cold therapy. So you do that, you mentioned for you in particular for mood. You said that's not the case for everyone, but there is a good amount of people who get that benefit. And so do you find for yourself it's more of a if you routinely do cold plunges, like it's kind of like a consistent benefit?

   4. PAPeter Attia16:36

      Mm-hmm.

   5. SPSpeaker16:36

      Or do you find-- do you ever have days where you're like, "I'm in a terrible mood, like I need to just step away from the computer, jump in"? Do you kind of use it both ways, or how do you think about that?

   6. PAPeter Attia16:46

      I occasionally do use it as the, um, total reset and, and, um... [lips smack] And by the way, I don't know that that even needs to be done in the most extreme version of a cold plunge. Like, I, I really think that having your face dipped in a bowl of cold water, I've talked about this in the past, can sort of stimulate the mammalian dive reflex. Um, so if you put your-- So you have a big enough bowl, you put your head into it, just even just covering your face, that can, in, in theory, I suppose, at least trigger an autonomic response that sort of upregulates the parasympathetic system, uh, via the vagus nerve, and that can tone down the sympathetic system. Actually, this is a great example of kind of coming back to a previous podcast. So the one with Joel Jamieson where we talked about HRV. I think he did a very good job in that podcast explaining that you don't wanna think about, um, one system being on, one system being off between parasympathetic and sympathetic. You just really wanna think about them always both being on, and it's just a question of the balance. Are you revving one up more than the other?

   7. SPSpeaker17:50

      And you mentioned that in addition to cold therapy, Anna talked about exercise can also be a mood stabilizer for people. Do you see that for you? I know you-

   8. PAPeter Attia17:59

      100%. Yeah, yeah, yeah. If you-- I mean, if you deprive me from exercise, it's, I, it's noticeable within a day.

   9. SPSpeaker18:08

      Interesting.

   10. PAPeter Attia18:08

       For sure.

   11. SPSpeaker18:09

       And when you work with patients, how do you think-- 'cause there's obviously a huge spectrum of this, right? And, you know, some of it can be as simple as, like, "I'm just not gonna look at my phone an hour before bed." Other can be deep addictions. And so how do you think in your work with patients of when you're starting to recommend, "Hey, let's just try these behaviors," versus, "Let's go see a specialist to work on this in a more nuanced, detailed manner"?

   12. PAPeter Attia18:39

       Yeah. So I, I think for the most part, we like to see people try to solve this on their own using neighborhood as the tool. So what do I mean by that? If I'm sitting around holding my phone, I'm looking at it frequently. There's no two ways about it. Like-- And by the way, I can be very good about not l- like, I can be very good about not looking at social media, but it's also 'cause I don't really like social media. But the truth of it is, if I'm sitting around and my phone is on my lap or it's in my pocket, I'm going to be checking email, I'm gonna be checking texts, I'm gonna be reading news quite often. So if I want to avoid that, I have to come up with an alternative, and that's where my bat phone is a good alternative, right? Like, if I'm going somewhere where I need a phone to make phone calls, but I don't wanna have anything to do, I just bring my second phone, my bat phone, which doesn't have email on it. It-- I don't even know the phone number. Nobody knows the phone number, so it never gets a text message. Um, it's basically just a device that makes calls, um, and has podcasts on it if I wanna listen to a podcast. But it's not... So, so that's something that I'm just going to look at less because I've fixed the neighborhood in, in a sense. Um, and so I think that's sort of generally what I try to get patients to think about is, yeah, like, how do you not have your phone in your room? How do you not have your phone, uh, with you for an hour before bed? Not because you're, like, white-knuckling it, but because you've come up with another thing in your routine that wouldn't have a phone with you. So if you go and do a sauna cold plunge before bed, it's easy to displace the phone. But if I say, "I want you to sit there and stare at the wall but not have your phone," that's a tougher ask.

   13. SPSpeaker20:33

       So another follow-up question here would be, like, you've talked, do archery. Every now and then you go hunting, and when you do, it's basically like being off the grid, right? So you're hiking, you're deep in the woods. It's not like you're kinda sitting around your house. There's no TVs. So during those periods of time, those handful of days, do you find that, you know, not being on your phone, not having technology, when you come back to the world, do you use it less? Is that kind of like a natural dopamine fast or no?

   14. PAPeter Attia21:03

       I, I wouldn't say so 'cause I don't think it's long enough. Um, now, that said, I, I do enjoy that. Like, I do... You know, I just came back from a, a, a trip a little while ago where we were, we were bow hunting in a very, very remote area, so there was no-- there's no Wi-Fi, there's no cell service. My phone didn't work once except for the one place where one guy had one of those little Starlink things that you could, you know... So once or twice a day, you could make a phone call or something. And, um, yeah, everything about that is cool, which you don't have to be hunting to do it, that you could just be camping in the right spot. But everything about, like, waking up super, super early, going to bed once the sun goes down, um, and not being inundated with, with anything, um, was great. And, and, and so, you know, I don't think that would constitute, you know, a fast, 'cause at least in my case, it's not nearly long enough. But, but it's, it's enjoyable nonetheless. It also probably maybe made me feel a bit better in knowing that I, I guess I don't have an addiction to that at least, because I also didn't experience withdrawal. I was, like, quite happy to not have the device.

   15. SPSpeaker22:07

       Awesome.

5. 22:08 – 25:44

   Feng Zhang episode: the potential of gene editing with CRISPR technology for treating diseases, and the challenges ahead

   1. SPSpeaker22:08

      Well, let's move on to the next one, which is Feng's podcast, heavily on CRISPR gene editing. Really interesting episode. Pretty technical at times, but also it's a topic I feel is talked about so much, right? Like, you hear CRISPR, you hear gene editing. We know-- We've written about PCSK9 gene editing and how that can have an impact on cardiovascular disease. So do you wanna kinda talk about your biggest takeaways, insights you learned from that?

   2. PAPeter Attia22:37

      Thank you for listening to today's sneak peek AMA episode of The Drive. If you're interested in hearing the complete version of this AMA, you'll want to become a premium member. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. So if you wanna take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. Premium membership includes several benefits. First, comprehensive podcast show notes that detail every topic, paper, person, and thing that we discuss in each episode. And the word on the street is nobody's show notes rival ours. Second, monthly Ask Me Anything or AMA episodes. These episodes are comprised of detailed responses to subscriber questions, typically focused on a single topic, and are designed to offer a great deal of clarity and detail on topics of special interest to our members. You'll also get access to the show notes for these episodes, of course. Third, delivery of our premium newsletter, which is put together by our dedicated team of research analysts. This newsletter covers a wide range of topics related to longevity and provides much more detail than our free weekly newsletter. Fourth, access to our private podcast feed that provides you with access to every episode, including AMAs, sans the spiel you're listening to now and in your regular podcast feed. Fifth, the Qualies, an additional member-only podcast we put together that serves as a highlight reel featuring the best excerpts from previous episodes of The Drive. This is a great way to catch up on previous episodes without having to go back and listen to each one of them. And finally, other benefits that are added along the way. If you wanna learn more and access these member-only benefits, you can head over to peterattiamd.com/subscribe. You can also find me on YouTube, Instagram, and Twitter, all with the handle PeterAttiaMD. You can also leave us a review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit peterattiamd.com/about, where I keep an up-to-date and active list of all disclosures. [outro music]

Episode duration: 25:44