#411 ‒ AMA #90: Strong convictions, loosely held: how Peter's views on fasting, keto, metformin, rapamycin, whole-body MRI, and exercise have changed

View the Show Notes Page for This Episode https://peterattiamd.com/ama90/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=261012-pod-ama90&utm_content=261012-pod-ama90-podfeed Become a Member to Receive Exclusive Content https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=261012-pod-ama90&utm_content=261012-pod-ama90-podfeed Sign Up to Receive Peter's Weekly Newsletter https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=261012-pod-ama90&utm_content=261012-pod-ama90-podfeed In this "Ask Me Anything" (AMA) episode, Peter looks back on 400 episodes of The Drive with another installment of "strong convictions, loosely held," revisiting some of the positions he has taken over more than eight years of the podcast. He explains why changing one's mind in response to new evidence, conversations with experts, and clinical experience is essential for practicing medicine well. Peter begins with nutrition, describing how his views on ketogenic diets, extended fasting, and the framework of dietary restriction, time restriction, and calorie restriction have evolved. He explains why he no longer takes metformin for longevity and discusses his growing uncertainty around rapamycin despite compelling animal data. Peter also revisits his views on cancer screening, including whole-body MRI and liquid biopsies for early detection. On exercise, Peter explains how his approach to cardiorespiratory training and the 80/20 Zone 2 framework has changed, particularly for people with limited time to train. He also shares why he has moved away from heavy barbell squats and deadlifts and how he now thinks about balancing benefit and injury risk. Throughout the episode, Peter emphasizes the importance of focusing on durable principles, strong foundations, and sustainable practices rather than chasing optimizations that provide marginal gains. If you're not a subscriber and are listening on a podcast player, you'll only be able to hear a preview of the AMA. If you're a subscriber, you can now listen to this full episode on your private RSS feed https://peterattiamd.com/members/private-podcast-feed/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=261012-pod-ama90&utm_content=261012-pod-ama90-podfeed or our website at the AMA #90 show notes page http://peterattiamd.com/ama90/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=261012-pod-ama90&utm_content=261012-pod-ama90-podfeed. If you are not a subscriber, you can learn more about the subscriber benefits here https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=261012-pod-ama90&utm_content=261012-pod-ama89-podfeed. We discuss: Strong convictions, loosely held: changing opinions as evidence, expert conversations, and clinical experience evolve [2:00]; Nutrition: Peter's evolving view of ketogenic diets, energy balance, and dietary dogmatism [5:30]; Extended fasting, autophagy, lean-mass loss, and who may benefit from prolonged fasting [12:00]; The dietary restriction, time restriction, and calorie restriction framework—and why GLP-1 agonists are tipping the balance toward calorie restriction [20:15]; Why Peter no longer views metformin as geroprotective for metabolically healthy people [24:45]; Rapamycin for longevity: compelling animal data, unresolved human dosing, and Peter's growing uncertainty [29:15]; The importance of early cancer detection, declining whole-body magnetic resonance imaging (MRI) quality, and more targeted alternatives [41:30]; Liquid biopsies for cancer screening: the NHS-Galleri trial, why early-stage rather than late-stage detection is what actually matters, and why the technology remains "fuzzy" [53:30]; Evolving exercise goals, the limitations of the 80/20 Zone 2 framework, and programming cardio at lower training volumes [1:00:00]; Exercise prescriptions for limited time, building a training habit, and becoming less dogmatic about forcing workouts [1:05:00]; Moving away from heavy squats and deadlifts, alternative exercises, and deliberate risk management [1:13:00]; Prioritizing principles, foundations, and sustainable practices over marginal optimization [1:21:30]; and More. Connect With Peter on Twitter https://twitter.com/PeterAttiaMD, Instagram https://www.instagram.com/peterattiamd/, Facebook https://www.facebook.com/peterattiamd/ and YouTube https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:10Dr. Peter Attia?

  Hey everyone, welcome to a sneak peek Ask Me Anything, or AMA, episode of the Drive Podcast. I'm your host, Peter Attia. 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. Or you can learn more now by going to peterattiamd.com/subscribe. So without further delay, here's today's sneak peek of the Ask Me Anything episode.

• 0:39Dr. Peter Attia?

  Welcome to Ask Me Anything, episode number 90. In today's AMA, we're reflecting back on the first 400 episodes of The Drive, with another episode of the "Strong Convictions Loosely Held" theme. So what do we do with this? Well, we walk through some of the biggest positions I've taken across the eight-plus years of this podcast, but then we revisit them by basically asking, where have the data taken us? What's changed, if anything? And as a result of that, of course, where am I today? So in this episode, we're going to talk about my evolving views on ketogenic diets, extended fasting as a longevity intervention,

• 1:18Dr. Peter Attia?

  and the DRTRCR framework, why I stopped taking metformin for longevity, and my shifting position on rapamycin, whole-body MRI and liquid biopsies for cancer screening, including why I think whole-body MRI data quality has actually gotten worse over time and not better, how my approach to cardio-respiratory training and the 80/20 Zone 2 framework has changed, especially for people with limited training time, and why I stepped away from heavy barbell squats and deadlifts, and how to think about risk management in strength training. If you're a subscriber and want to watch the full video of this podcast, you can find it on the show notes page. And if you're not a subscriber, you can watch

• 2:02Dr. Peter Attia?

  a sneak peek of the video on our YouTube page. So without further delay, I hope you enjoy our celebration of 400 episodes together with AMA number 90.

• 2:16Speaker 01

  Peter, welcome to another podcast. How are you doing?

• 2:18Dr. Peter Attia?

  Very good, thank you. You?

• 2:20Speaker 01

  Doing good, doing good. So today, we are celebrating 400 episodes, about eight years. So we recently crossed this, and usually what we do is every now and then we'll look back at kind of a reflection episode. In the past, we've always referred to them as "Strong Convictions Loosely Held." And so I think as we start, and before we get into specific topics, do you kind of want to remind people about what that term means to you, where you heard about it, and why you think it's so important?

• 2:46Dr. Peter Attia?

  Yeah, it's a term that I first heard from a friend who ran a hedge fund, and obviously this was through the lens of his investment thesis, which was that obviously you needed strong convictions, because you're putting real capital behind the thesis. But those convictions had to be loosely held, because the moment new information or contradictory information showed itself, you kind of had to be willing to check your ego at the door, say, "Maybe I was wrong, and how do I need to change things?" But I always thought that that frankly was a great view of how to think about everything, where there's actual information at play. And obviously, medicine and science are great examples of that. So I've been around many really, really great scientists, and one of the characteristics

• 3:29Dr. Peter Attia?

  they all have in common is they're not married to a particular thesis being right, they're married to sort of getting things as right as possible and reducing uncertainty by following the data wherever those data take them. So I think it's important that we are revisiting our assumptions. And as someone asked me once, "If you were to write Outlive 10 years from now, do you think it would be the same book that you wrote three years ago?" And I would say, "No." In fact, that would be concerning if it were the same book in 10 years as it was at the time it was written, because it would either suggest "I'm too rigid in my thinking," or "Science has made no progress." And I think both of

• 4:11Dr. Peter Attia?

  those would be challenging. So yeah, that's loosely how we think about this episode.

• 4:17Speaker 01

  And Peter, when you're kind of looking at your opinions and how you're thinking about things and how they evolved, where does that traditionally come from? What are the triggers that are causing you to potentially change your opinion or how you look at things?

• 4:31Dr. Peter Attia?

  I think it's a combination of, obviously, things that change in the literature, but scientific progress is, by its very nature, somewhat glacial and episodic, right? It's not like, it doesn't just progress at the same rate. But, so I think the other sources of learning for me, and things that forced me to change, maybe things I once held, would be the podcast itself, right? There's an opportunity I get most weeks to sit down with someone who's far more of an expert in a subject matter than I am, and both in preparing for that discussion, having that discussion, I'm learning something that often changes, I mean, almost always changes something in how I think. And then obviously, you have,

• 5:12Dr. Peter Attia?

  as every doctor hopefully appreciates, all of our patients are kind of our teachers, right? So we learn a lot because we're seeing what happens in a clinic with patients, and we're, you know, we're going to talk about some of these things today, frankly. So, basically, I think all of these things taken together, whether it be literature, conversations with experts, and seeing what actually happens in the clinic, I think a lot of times, these things continue to converge, and the views don't change much. And other times, the view just gets more nuanced, and you start to carve out edge cases and exceptions. And then sometimes, it actually causes you to change course completely. And obviously, that's what I think this episode's all about, and what makes this type of episode, for me personally,

• 5:57Dr. Peter Attia?

  quite enjoyable.

• 5:59Speaker 01

  I think as we start this, I think the topic that makes the most sense to start at, which is everyone's favorite, nutrition. So kind of very early on, way back in the day, you were a big proponent of the keto diet. You were also an early adopter and advocate for kind of extended fasting, and what that could potentially do from a longevity perspective. And so kind of where are you now on those things, and how has your opinion changed?

• 6:26Dr. Peter Attia?

  Well, my original thinking, I'll start with the diet thing, was really driven by this insulin model of obesity. So metabolic disease was, and obviously remains, kind of not just one of the four horsemen of chronic disease, but kind of the foundational problem, right? So it's the one thing where, as metabolic health gets worse, your risk of all other chronic diseases essentially goes up. And in my own journey of nutritional experimentation, carbohydrate restriction was proving to be very beneficial. And as you stepwise move down the plank of carbohydrate restriction, you're going to pretty quickly find yourself

• 7:08Dr. Peter Attia?

  at a place, which is generally a line in the sand of ketogenic diets or not, right? Because at some point, carbohydrate intake gets so low that you're not providing enough glucose for your brain, but if it's still a little high, and it's too high to allow your body to switch over into ketosis, then you're not getting enough supplemental energy for your brain, and you're in that kind of no man's land of hell. And so I remember getting to that point, and then deciding, well, you know, I at that point had been reading a lot about ketogenic diets, and decided, "Look, I'm going to give this thing a shot." So anyway, so that my own journey starts with my own experience, which was very positive. I know I get sort of labeled as someone who's anti-keto diets and stuff like that by various people out there. And I just find that to be the most comical critique

• 7:53Dr. Peter Attia?

  of me, because not only was I on a ketogenic diet for three years, it was probably the best I ever felt. I look back at what those three years were like, and every element of it was very positive for me. There are other reasons, obviously, I chose to abandon it. Nevertheless, it reinforced the model in my mind that the relationship between carbohydrates, insulin, hyperinsulinemia, lipogenesis, et cetera, was, you know, sort of, it all made sense that then a ketogenic diet would sort of fix these problems. I think there were also lots of compelling data with animals and humans showing the improvements in glycemic control, insulin sensitivity, liver visceral fat, et cetera,

• 8:36Dr. Peter Attia?

  and other metabolic markers improving. And as I said, I certainly reinforced that. Now, here's what's different. I abandoned the ketogenic diet, basically because I was just tired of being that restrictive in my eating. I mean, I was very strict in my ketosis. I think, you know, I also logged unprecedented amounts of data during this process. And I think over a three-year period of time, you know, my average morning fasting beta hydroxybutyrate level was, you know, 1.8 to 2 millimoles, something in that range. So this wasn't like, I wasn't sort of a light ketosis guy. And then, of course, it would get much higher during the day, depending on what I was eating, because I was mostly

• 9:18Dr. Peter Attia?

  eating fat. So my abandoning the ketogenic diet was independent of my views of the ketogenic diet, and to this day, I still view it as an effective diet. What has changed is my belief as to why it works. You see, I used to believe that the diet worked through insulin suppression. But today, I don't think that's the case. Today, I think the diet works for the same reason many restrictive diets work, which is, it makes it easier to control energy intake, even if you don't have to think about it deliberately, which, to be clear, I never did, right? And of course, I wasn't losing much weight on a ketogenic

• 10:00Dr. Peter Attia?

  diet, because I'd already lost most of the weight I was trying to lose just from carbohydrate restriction. But when I see people who are successful on ketogenic diets, they often report that they feel quite satiated. And I think that has to do with the type of foods that they're consuming, which satiate them more than carbohydrates. And I also believe there's something to be said for when you are oxidizing fatty acids, that in and of itself is providing fuel endogenously, which is happening, obviously, during a period of weight loss. So it's a subtle point, but it's worth making, because it does reflect a change in my viewpoint, which is that the metabolic dysfunction, the visceral fat

• 10:43Dr. Peter Attia?

  accumulation, the ectopic fat accumulation, the insulin sensitivity deteriorating, all of these things are the result of the energy imbalance. And hyperinsulinemia is along for the ride. But if you magically... Address the hyperinsulinemia without addressing the energy imbalance, you're not going to fix these problems. And the easiest way to see that is to watch a person who's on a ketogenic diet, who for whatever reason is still in energy imbalance. So they're still going to have lower levels of insulin, but they're not going to lose weight and they could even gain weight. So you could gain weight on a ketogenic diet if you're out of energy balance. So that's, that's sort of the long and short of my views on that.

• 11:25Dr. Peter Attia?

  As a result, I think it's made me less, I mean, much less dogmatic about the strategy or the tactics that a person employs when it comes to reducing, you know, energy intake. I really don't have a strong preference when a patient is at a point where they need to reduce intake. Once a few principles are met, and we've obviously talked a lot about those things, right? I really am pretty adamant about people maintaining the, the right amount of protein. And at a minimum, I want them hitting 1.4 grams per kilogram of body weight. But if they can accomplish that on a ketogenic diet, on a low-fat diet, on a mostly pescatarian diet. I mean, again, it just doesn't really matter as much to me as it once did.

• 12:09Dr. Peter Attia?

  So yeah, I think that's, that's probably a big point around the, the sort of my previous dogmatism around nutrition.

• 12:17Speaker 01

  And now looking at extended fasting, do you want to talk about kind of what was your initial motivation there? And where you're thinking as a bulk?

• 12:26Dr. Peter Attia?

  Yeah, I mean, I think it's sort of similar. Again, a lot of things with me begin from a place internally, right? Where I'm doing something and I'm trying to push the boundaries of it personally. So for about a three-year period of time, I was doing a quarterly fast and it would be anywhere from seven to 10 days once a quarter. And then on the other two months of the quarter, I would do a three-day fast. And what was my logic for this? I mean, to be clear, I was not trying to lose weight. I was at a weight that was perfectly reasonable. But I was really fascinated by this idea that with enough nutrient deprivation, we could promote enough autophagy that it would have real health benefits.

• 13:10Dr. Peter Attia?

  And just to remind folks what autophagy is. Autophagy is the process by which cells break down and recycle old intracellular proteins and structures. So the name auto self-phyg eating. It's literally cells that are kind of eating themselves. And, and this is a very important process, obviously long, long conserved in evolution, because when nutrients are scarce, the body has to basically reuse and recycle things. Now, the benefit of this, of course, is that what, what is the body going to do when it needs to reuse and recycle things? It's not going to start with the best stuff. It's going to start with the worst stuff. So if you have cells that are heading towards senescence, if you have cells that are developing mutations,

• 13:54Dr. Peter Attia?

  the thinking goes, hey, that's where we're going to start. Those are the cells we're going to get rid of and recycle for their constitutive components. And again, in preclinical models, extended fasting clearly does this. So there's, there's little doubt that extended fasting promotes autophagy. As a little aside, Nick, and I haven't looked at the literature on this in a couple of years. So maybe what I'm saying, someone will say, no, Peter, we actually, you know, look at so-and-so study. But, but it wasn't really clear how many days of fasting were necessary to get into, quote, high autophagy. Because autophagy is not digital, it's analog. It's not like you have no autophagy and then you cross a threshold and now you have autophagy in a digital switch.

• 14:38Dr. Peter Attia?

  It's, it's sort of ramps up, kind of like ketosis. Now, in ketosis, we have a threshold we use. It's about somewhere between 0.5 and 1 millimol resting or fasting. We don't even have a unit of measure in autophagy to do that. But having spoken with, you know, the experts on this subject matter and looking at preclinical data, somewhere around three days seemed to be where, where you could really sort of juice autophagy levels beyond what you would get from exercise or other things like that. Okay, so then the question becomes, well, why aren't you doing that still, Peter? And again, I think there were several reasons for that. But I think what changed most was kind of the evidence, but also the cost.

• 15:23Dr. Peter Attia?

  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 want to 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.

• 16:06Dr. Peter Attia?

  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

• 16:47Dr. Peter Attia?

  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 want to 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 peteratiaMD. You can also leave us a review on Apple Podcasts

• 17:31Dr. Peter Attia?

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• 18:16Dr. Peter Attia?

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