#370 - AMA #76: Peter evaluates longevity drugs, aspirin for CVD, and strategies to improve muscle mass — promising, proven, fuzzy, noise, or nonsense?

Speaker 1 Hey everyone, welcome to a sneak peek, Ask Me Anything, or AMA episode of the Drive podcast. I'm your host, Peter Attia.

Speaker 1 At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created.

Speaker 1 Or you can learn more now by going to peteratiamd.com forward slash subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode.

Speaker 1 Welcome to Ask Me Anything AMA, episode number 76.

Speaker 1 In today's AMA, we revisit the proving, promising, fuzzy, noise, nonsense scale and apply it to a variety of commonly inquired about and hot button topics.

Speaker 1 We start with a quick reset on what each bucket means and define them, of course. And then we walk through every topic where we're going to land on.

Speaker 1 So the goal of this episode is that if you're coming to this topic without any previous background or you just want the TLDR, this is the place for you. We group the topics by the intended outcome.

Speaker 1 There are three categories today. Drugs for giro-protection, where we cover GLP-1 agonists, SGLT2 inhibitors, methylene blue, and telomere lengthening supplements.

Speaker 1 Talk about low-dose aspirin for C V D prevention. and then we look at interventions to improve muscle mass, talking specifically about protein but also folastatin gene therapy.

Speaker 1 If you're a subscriber and want to watch the full video of this podcast, you can find it on the show notes page.

Speaker 1 And if you're not a subscriber, you can watch the sneak peek of this video on our YouTube page. So, without further delay, I hope you enjoy AMA 76.

Speaker 1 All right,

Speaker 1 Peter, Otia,

Speaker 1 doctor, podcaster, author,

Speaker 1 speaker, bad chess player. How are you doing today? Hey, hey, hey, hey, hey, hey, hey.
You could say shepherd in there. You don't have to

Speaker 1 take sheep shots.

Speaker 1 Shepherd of diabetic sheep, race car driver. Anything else missing? Oh, that's good.
That's good. All right.
I just didn't want to forget the diabetic sheep out there. That's true.
That's true.

Speaker 1 How's the day going today? Started out good, then took a little dip with the follow-up chess match. But there's a recurring theme here that you, I know you just love picking this scab.

Speaker 1 Well, I just sometimes you think about feats like Tom Brady, right? Like what he went through. Greatest of all time.
Right. Yeah.
People who come back from injuries.

Speaker 1 DeMar 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?

Speaker 1 Listen.

Speaker 1 We all started playing at the same time. Gagachar just won the tour again.
Went through two in a row. Grueling.

Speaker 1 Not as mentally tough as what you went through, though, a month ago. I would argue what I go through on the daily,

Speaker 1 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.

Speaker 1 We need to have Tom on the podcast and you should ask him about it. Which one was harder? All those Super Bowls.
Is it harder to be down 28 to three having thrown a pick six in the Super Bowl or

Speaker 1 succumbing to

Speaker 1 an eight-year-old's gambit, which is tougher? To be fair, there is a real chance that eight-year-old might have talked more trash than what was going on in the Super Bowl, which says something.

Speaker 1 Yep.

Speaker 1 All right. So today's AMA, not about chess, going to be a little different.

Speaker 1 So what we're going to do is cover a variety of topics, looking at it through a certain lens, which is we are going to 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.

Speaker 1 And instead of going super deep in them, we're going to kind of summarize them into how you think about them. And we're going to do it into five different buckets.

Speaker 1 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.

Speaker 1 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.

Speaker 1 And it allowed us to kind of look at them in an apples to apples comparison with what we know about them and how people should be thinking about it.

Speaker 1 So in today's episode, we are going to look at some giro-protective drugs like GLP-1s, things like Ozempic, SGLT2 inhibitors, both of which we talked about before.

Speaker 1 We're going to look at methylene blue and telomere lengthening supplements. Those are kind of newer.
We're going to look at what we know about low-dose aspirin and cardiovascular disease prevention.

Speaker 1 And then we're going to look at interventions that can help improve muscle mass, things like protein, folastatin gene therapy, etc. Hopefully a good variety of things for people.

Speaker 1 Hopefully kind of a way to go through it where people can kind of look, get clear, clean takeaways. With that said, anything you want to add before we get rolling?

Speaker 1 No, but maybe I will just remind people, or for folks who are new to the program, what these categories mean.

Speaker 1 So you mentioned five, and we're starting from the most promising or the closest to quote-unquote truth, which we're calling proven, although I put put proven in quotes because technically nothing in biology is proven, right?

Speaker 1 It's not like mathematics where you prove something and write QED at the end and never have to think about it again. So proven would be as close to well-established claim as you're going to find.

Speaker 1 The implication for us, of course, is you've got lots of high-quality, consistent data. The category beneath that would be promising.
This is a category where the claims look good.

Speaker 1 There are data to support it, but maybe we're still waiting on replication or maybe most of the data are moving in one direction, but not all of it, or something like that.

Speaker 1 Category beneath that, we call fuzzy. And this means there are some data around the claim, but they are really inconsistent and incomplete.

Speaker 1 So overall, you would say the data quality here is not that great, but there's probably a signal. Beneath that, we have noise.

Speaker 1 So here we have something where there are just frankly no real meaningful results.

Speaker 1 So noise is something that it's not that I'm saying you shouldn't pay attention to it, but you clearly don't want to be distracted by it.

Speaker 1 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.

Speaker 1 So, again, nonsense means we actually have data, and the data refute the claim being made. So, as far as we can tell, this is as close to disproven as you'll be.

Speaker 1 So again, those are the five categories. Just kind of keep that in mind as we apply our judgments to these things.
And keep in mind as well that these are fluid.

Speaker 1 Things can move up and down these chains in the presence of new information. Yeah.
And I think I always like to anchor people to this.

Speaker 1 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.

Speaker 1 You see it a lot in nutrition where it's like you just get in a camp and you stay with it.

Speaker 1 Do you just want to talk a little bit about your idea of strong convictions loosely held and why you think it might be counterintuitive when people 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 signs for science.

Speaker 1 Yeah, look, I think first and foremost, that's an attribute of great scientists.

Speaker 1 So if you look at what separates good scientists from great scientists, that would probably be one of the characteristics. A great scientist is not married to being right.

Speaker 1 They're married to knowing what is right, and they're going to go wherever the data take them.

Speaker 1 But honestly, the first time I heard that expression to have strong convictions loosely held was actually from a friend of mine who at the time was running a hedge fund. He's since retired.

Speaker 1 But he said, look, that's the key to being a good investor is you have to have strong convictions because you're going to be putting a lot of capital at risk.

Speaker 1 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.

Speaker 1 And the reason I think that this is such an important part of investing is in science, if you're wrong, the price is not that severe.

Speaker 1 In fact, without calling out or embarrassing anybody, there are lots of people who have taken positions on things that are just so patently incorrect 20 and 25 years later, and yet they just can't let go of their baby.

Speaker 1 They can't kill their baby. And so, frankly, they just make fools out of themselves continuing to cling to ridiculous beliefs.
But there's actually no real price they're paying for that.

Speaker 1 Other than within the scientific community, they're laughed at. 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.

Speaker 1 And so in the final analysis, the dollars talk louder than anything else.

Speaker 1 And if you continue to double down on horrible positions, you will lose the money of your LPs and ultimately you will be broke.

Speaker 1 So I think that's sort of why it's a great idea to be thinking about through the lens of how an investor functions. And so I think we just have to all try to do that.
It's hard.

Speaker 1 It's hard to kill your babies. But that was the expression.

Speaker 1 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 trying to put hypotheses together and make sense of what I was seeing.

Speaker 1 You can have the most beautiful, beautiful hypothesis ever, and it can be categorically slayed by ugly facts. And that's paraphrasing a quote.

Speaker 1 God, I don't remember who actually said that quote, but it's a sort of famous quote in science. Yeah, I think it's just good for people to kind of anchor that too.

Speaker 1 So starting off, if you had to put the following statement into one of those categories, where would it be? Which is

Speaker 1 the next in-house tournament, Peter Peter Attia takes first place.

Speaker 1 Listen, I believe I have the potential to beat my young boys in chess, provided I don't get distracted by the smack talk.

Speaker 1 In my defense today, by the way, I know you don't play chess, but just so you understand, I promoted a pawn to a second queen on the 25th move.

Speaker 1 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 on material before that promotion. This was a bloodbath.

Speaker 1 And then he starts yapping so much and makes what looks like an idiotic blunder, exposing his rook to my newest queen. So of course, I take the free rook.

Speaker 1 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.

Speaker 1 So he sacrificed his rook to put his bishop in a way to basically create what's called a battery against my king and the next move he checkmated me so 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 i think i have a good chance to win the next in-house tournament i do love your crypt tonight is

Speaker 1 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, wherever it is.

Speaker 1 There could literally be a sitcom of me going through my life just getting broken down by eight-year-olds, just getting put in my place.

Speaker 1 It's like the Seinfeld episode where the shrimp comment, a day later, he rethinks of what the comeback should have been.

Speaker 1 I just anticipate that's you like going to sleep at night being like, oh, man, when when Aries said this, if I would have responded with this, I would have got him so bad.

Speaker 1 Next time, next time, I'm not going to let that eight-year-old talk that trash to me. So good.

Speaker 1 Well, real thing we're going to start with, geoprotective drugs. So there's a lot of questions about drugs that have metabolic health effects and what that means for.
anti-aging.

Speaker 1 So instead of just looking at this improves metabolic health, is there something special about those that can also be anti-aging?

Speaker 1 And 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.

Speaker 1 But outside of that, the biggest drug that is in the news all day, every day, GLP1s, Ozempic, Trezepatide, Mogovi, you name it. Everyone's heard of it.
We've done a lot about that.

Speaker 1 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.

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