Peter evaluates longevity drugs, aspirin for CVD, & strategies to improve muscle (AMA 76 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 – 6:29

   A scale for evaluating scientific claims: proven, promising, fuzzy, noise, or nonsense

   1. SPSpeaker0:11

      Peter Attia, doctor, podcaster, author, speaker, bad chess player. How you doing today?

   2. PAPeter Attia0:21

      Hey, hey, hey, hey, hey, hey, hey. You could say shepherd in there. You don't have to-

   3. SPSpeaker0:25

      Oh, true

   4. PAPeter Attia0:25

      ... you don't have to take cheap shots. [chuckles]

   5. SPSpeaker0:27

      Yeah. Shepherd of diabetic sheep, race car driver. Anything else missing?

   6. PAPeter Attia0:35

      No, that's good.

   7. SPSpeaker0:35

      [chuckles] That's good. All right. Yeah, I just d- didn't want to forget the diabetic sheep out there.

   8. PAPeter Attia0:42

      That's true. That's true.

   9. SPSpeaker0:44

      How's the day going today?

   10. PAPeter Attia0:45

       Started out good, then took a little, little, little dip with the follow-up chess match, but...

   11. SPSpeaker0:52

       It's just the in-house tournament. It's getting pretty rough.

   12. PAPeter Attia0:53

       There's a, there's a recurring theme here that you-- I know you just love picking this scab.

   13. SPSpeaker0:57

       Well, I just... It's sh-- You know, sometimes you think about feats like Tom Brady, right? Like what he went through.

   14. PAPeter Attia1:05

       Greatest, greatest of all time, right.

   15. SPSpeaker1:07

       Yeah. Um, people who come back from injuries, right? Damar Hamlin, like, almost died, came back and played. I mean, like, you getting second in a four-person in-house chess tournament with two children has to be up there, right?

   16. PAPeter Attia1:24

       Li- listen. [chuckles]

   17. SPSpeaker1:28

       Like-

   18. PAPeter Attia1:28

       We all started playing at the same time

   19. SPSpeaker1:30

       ... Praggnarozh, Praggnarozh just won the tour again.

   20. PAPeter Attia1:32

       That's right.

   21. SPSpeaker1:32

       Right? Went through two in a row. Grueling. Not as mentally tough as what you went through, though, a month ago, right?

   22. PAPeter Attia1:42

       I would argue what I go through on the daily trying to just make sure I don't get beat by an eight-year-old in chess is at least on par mentally with some of the feats you're talking about.

   23. SPSpeaker1:55

       We need to have Tom on the podcast, and you should ask him about it. Which one was harder? All those Super Bowls-

   24. PAPeter Attia2:00

       Is it harder to be down 28 to three, having thrown a pick six in the Super Bowl, or succumbing to an eight-year-old's gambit? Which is tougher?

   25. SPSpeaker2:16

       To be f- [chuckles] to be fair, there is a real chance the eight-year-old might have talked more trash than what was going on in the Super Bowl, which says something.

   26. PAPeter Attia2:24

       [chuckles] Yep.

   27. SPSpeaker2:27

       [chuckles] All right. So today's AMA, not about chess. Gonna be a little different. So what we're gonna do is cover a variety of topics, looking at it through a certain lens, which is we are gonna take concepts and things that we've talked about before, some new things that we haven't talked about before that we get asked about a lot, and instead of going super deep in them, we're gonna kind of summarize them into how you think about them, and we're gonna do it into five different buckets, and those buckets are proven, promising, fuzzy, noise, nonsense. People who have listened for a bit will remember this. We did this in episode 300 of the podcast, which was back in May 2024. So it's been a little bit, but people really liked it because it allowed us to cover a variety of topics, it allowed us to summarize them, and it allowed us to kinda look at them in an apples to apples comparison with what we know about them and how people should be thinking about it. So in today's episode, we are gonna look at some geroprotective drugs like, uh, GLP-1s, things like Ozempic, SGLT2 inhibitors, both of which we talked about before. We're gonna look at methylene blue and telomere-lengthening supplements. Those are kinda newer. We're gonna look at what we know about low-dose aspirin and cardiovascular disease prevention, and then we're gonna look at interventions that can help improve muscle mass, things like protein, follistatin gene therapy, et cetera. So hopefully a good variety of things for people. Hopefully kind of a way to go through it where people can kinda look, get clear, clean takeaways. With that said, anything you want to add before we get rolling?

   28. PAPeter Attia4:11

       No, but maybe I will just remind people, or for folks who are new to the program, what these categories mean. Um, so you mentioned sort of five, and we're starting from kind of the most promising or the, the closest to, quote-unquote, "truth," which we're calling proven, although I put proven in quotes because technically nothing in biology is proven, right? It's not like mathematics, where you prove something and write QED at the end and never have to think about it again. Um, so proven would be as close to well-established claim as you're gonna find. The implication for us, of course, is you've got lots of high quality, consistent data. Um, the category beneath that would be promising. Uh, this is a category where the claims look good. There are data to support it, um, but maybe we're still waiting on replication, um, or maybe there's, you know, most of the data are moving in one direction but not all of it or something like that. Category beneath that we call fuzzy, and this means there are some data around the claim, but they are really inconsistent and incomplete. Um, so overall, uh, you would say the data quality here is not that great, but there, there, you know, there, there's, there's probably a signal. Beneath that, uh, uh, we have noise. Um, so here we have something where there are just frankly no real meaningful results. Um, so, you know, noise is something that-- it's not that I'm saying you shouldn't pay attention to it, but you clearly don't wanna be distracted by it, and it's best to wait and see if noise declares itself by going up to fuzzy with the presence of some data as it works its way up the chain, or whether data actually emerge that put it in the final category, which is actual nonsense. So again, nonsense means we actually have data, right? And the data refute the claim being made. Um, so as far as we can tell, this is as close to disproven as, as you'll be. So again, those are the five categories. Just kinda keep that in mind as we apply our judgments to these things. And keep in mind as well that these are fluid. Um, things can move up and down these chains in the presence of new information.

   29. SPSpeaker6:28

       Yeah, and I think

3. 6:29 – 12:27

   Strong convictions, loosely held: the mindset that separates great scientists from the rest

   1. SPSpeaker6:29

      I always like to anchor people to this, and so we've talked about it before, but I do think it's helpful, which is sometimes I think in today's day and age where people are very confident in their opinions and usually kind of stick to them, you see it a lot in nutrition, where it's like you just get in a camp and you stay with it. Do you just want to talk a little bit about like your idea of like strong convictions loosely held and why you think it might be counterintuitive when people like change mind and something goes from proven to promising or it goes up and down, but just how you think about when new data comes, you just have to be unemotional to it and just take science for science?

   2. PAPeter Attia7:10

      Yeah, look, I think first and foremost, that's an attribute of great scientists. So if you, if you look at what separates good scientists from great scientists, that would probably be one of the characteristics, right? A great scientist is not married to, um, being right. They're married to knowing what is right, and they're gonna go wherever the data, uh, take them. Um, but honestly, the, the first time I heard that expression, to have strong convictions loosely held, was actually from a friend of mine who, uh, uh, at the time was running a hedge fund. He's, he's since retired. Um, but he said, "Look, that's the key to being a good investor is you have to have strong convictions because you're gonna be putting a lot of capital at risk. Um, but those convictions have to be loosely held, so the moment that data emerge that change your thesis for investment, you have to be flexible enough to move as opposed to double down." And the reason I think that this is such an important [chuckles] part of investing is, um, in science, if you're wrong, the price is not that severe. Um, in fact, uh, without calling out or embarrassing anybody, there are lots of people who have taken positions on things that are just so patently incorrect, you know, 20 and 25 years later, and yet they just can't let go of their baby, right? They can't kill their baby. And so frankly, they just make fools out of themself continuing to cling to ridiculous beliefs. But there's actually no real price they're paying for that, right? Other than within the scientific community, they're laughed at. Um, but you can't be an investor, you can't be a money manager with that type of mentality because you'll be out of business, right? Um, and so in the final analysis, the dollars talk louder than anything else, and if you continue to double down on horrible positions, you will, um, lose the money of your LPs and ultimately you will, you will be broke. So I think that's sort of why it's, it's a great idea to be thinking about through the lens of how an investor functions. And, and so I think we just have to all try to do that. It's hard. It's hard to kill your babies. Um, but that was the expression. Those were the exact words that were used when I first showed up in the lab and first started doing experiments and first started getting my data and trying to put hypotheses together and make sense of what I was seeing. It was, "You can have the most beautiful, beautiful hypothesis ever, and it can be categorically slayed by ugly facts," and that's paraphrasing a quote. Uh, God, I don't remember who actually said that quote, but it's a, it's a, it's a sort of famous quote in science.

   3. SPSpeaker9:48

      Yeah, I think it's just good for people to kind of anchor that, too. So starting off, if you had to put the following statement into one of those categories, where would it be? Which is, the next in-house tournament, Peter Attia takes first place.

   4. PAPeter Attia10:03

      [chuckles] You're not gonna let this go. Listen, um, I believe I have the potential to beat my young boys in chess, provided I don't get distracted by the smack talk, right? I think in all-- in, in my defense today-- By the way, just, I know you don't play chess, but just so you understand, I promoted a pawn to a second queen on the 25th move. Okay, do you understand what an advantage I had in this game today? I've got two queens on the board, and I was ahead on material before that promotion. This was a bloodbath, and then he starts yapping so much and makes what looks like an idiotic blunder, exposing his rook to one of my new, to my newest queen. So of course, I take the free rook. But I was so dumb when I did it that I didn't notice that he moved his bishop out of the way, what looked like a blunder, so he sacrificed his rook to put his bishop in a way to basically, uh, create what's called a, a battery against my king. In the next move, he checkmated me. So, you know, you could say, "Okay, I got beat." Yes, I did, but part of it is I was distracted by how much he was yapping. So all I really need to do to up my game is just not get distracted, and then I, I think I have a good chance to win the next in-house tournament.

   5. SPSpeaker11:31

      I, I do love your kryptonite is second graders who talk trash, whether it's chess, whether it was the kid who was just giving you tons of crap for drinking a diet soda at the school lunch.

   6. PAPeter Attia11:46

      [laughs]

   7. SPSpeaker11:47

      Wherever it is.

   8. PAPeter Attia11:48

      There could literally be a sitcom of me going through my life just getting broken down by eight-year-olds. Just, just getting put in my place.

   9. SPSpeaker11:58

      It's like the Seinfeld episode where, like the shrimp comment, where a day later he rethinks of what the comeback should have been.

   10. PAPeter Attia12:05

       [laughs]

   11. SPSpeaker12:06

       I just anticipate that's you, like going to sleep at night being like, "Oh, man, when Ari said this, if I would've responded with this, I would've got him so bad. Next time, next time I'm not gonna let that eight-year-old talk that trash to me."

   12. PAPeter Attia12:22

       So good.

   13. SPSpeaker12:24

       All right. Well, real thing we're gonna start with,

4. 12:27 – 14:42

   GLP-1 receptor agonists: are there benefits beyond improving metabolic health and promoting weight loss?

   1. SPSpeaker12:28

      geroprotective drugs. So there's a lot of questions about drugs that have metabolic health effects and what that means for anti-aging. So instead of just looking at this improves metabolic health, is there something special about those that can also be anti-aging? And

   2. PAPeter Attia12:48

      On a side note, just it'll be good to explain what geroprotective drugs are. We've done it before, but I think it's good for a quick reminder. But outside of that, the biggest drug that is in the news all day, every day, GLP-1s. Ozempic, Triseptide, Wegovy, you name it, everyone's heard of it. We've done a lot about that. So the question is, do we know anything if they have a unique anti-aging effect that actually improves lifespan outside of the metabolic health effects they have? Thank you for viewing this sneak peek of an Ask Me Anything episode of The Drive. As a premium member, you'll get immediate access to the full AMA episode you just watched a sneak peek for, our entire back catalog of AMA episodes, and all future AMA episodes. You'll get longevity-focused premium articles packed with actionable insights. You'll get unrivaled show notes for each and every episode of The Drive, and much more. Become a premium member today at peteratiamd.com forward slash subscribe. 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 peteratiamd.com forward slash about, where I keep an up-to-date and active list of all disclosures.

Episode duration: 14:46