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

Reflecting on four hundred episodes

0:00Hey, everyone. Welcome to a sneak peek, ask me anything or AMA episode of the drive podcast. I'm your host, Peter Atiyah. 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 peteratiyahmd.com forward slash subscribe. So without further

0:31delay, here's today's sneak peek of the ask me anything episode. 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

1:06us? 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, 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.

1:38How my approach to cardiorespiratory training and the 80-20 zone two 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 a sneak peek of the video on our YouTube page. So without further delight, I hope you enjoy our celebration of 400 episodes together with AMA number 90.

2:10Peter, welcome to another podcast. How are you doing? Very good. Thank you. You? 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, before we get into specific topics, do you kind of want to remind people about what that

2:42term means to you, where you heard about it, and why you think it's so important? 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 needed strong convictions, but 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

3:13things? And I always thought that that frankly was, 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 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, wherever those data take them. So I think it's, um, important that we are revisiting

3:47our assumptions. And as someone asked me once, you know, if you were to write Outlive 10 years from now, do you think it would be the same book that you wrote, you know, three years ago? And I would say, no, I, in fact, that would be concerning if it were the same book in 10 years as it was at the time it was written. Cause it would either suggest I'm too rigid in my thinking or science has made no progress. And I think both of those would be, would be challenging. So yeah, that's loosely how we think about this episode. And Peter, when you're kind of looking at your opinions and how you're thinking

4:21about 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? I think it's a combination of obviously things that change in the literature, but, you know, scientific progress is, you know, 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, of learning for me and things that forced me to change, maybe things I once held would be the podcast itself,

4:55right? There's a 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 a discussion, I'm learning something that often changes. I mean, almost always changes something in how I think. And then obviously you have, uh, as every doctor hopefully appreciates, all of our patients are kind of our teachers, right? So we learn a lot because we're, we're seeing what happens in a clinic with patients and we're, uh, you know, we're going to talk about some of

5:26these things today, frankly. Uh, so, so, you know, so, so basically I think all of these things taken together, whether it be literature conversations with experts and seeing what, what actually happens in the, 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 is all about. And what, what makes this type of episode for me personally, quite enjoyable. I think as we start this, I think the topic that makes the most

Evolving views on ketogenic diets

6:02sense to start at, which is everyone's favorite nutrition. So kind of very early on way back in the day. Um, 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? Well, my original thing, I'll start with the diet thing was, was really driven by this insulin model of obesity. So

6:33metabolic 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, it's the one thing where as, 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

7:07going to pretty quickly find yourself 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, 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

7:37decided, 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, by various people out there. And I just find that to be the most comical critique 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, you know, what those three years were like and every element of it was, was very positive for me. There are other reasons. Obviously I chose to abandon it. Nevertheless, it reinforced the

8:12model in my mind that, um, 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, with animals and humans showing the improvements in glycemic control, insulin sensitivity, liberal liver, visceral fat, et cetera, 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

8:48of 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 millimole, 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 eating fat. So my abandoning the ketogenic diet was independent of my views of the ketogenic

9:25diet. 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

9:55deliberately, which to be clear, I never did, right? Now, of course, I wasn't losing much weight on a ketogenic 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

10:28happening, 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 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

11:03going 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 sort of the long and short of my views on that. 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 energy intake. I really don't

11:38have 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 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. So yeah, I think that's probably a big point around the sort of my previous dogmatism around

Extended fasting and longevity

12:15nutrition. 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 bulb? 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

12:48other 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. And just to remind folks what autophagy is, autophagy is the process by which cells break down and recycle old intracellular proteins and

13:20structures. So the name auto-self-phagy eating, it's literally cells that are kind of eating themselves. 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 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, the thinking goes, hey, that's

13:56where 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 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 look at so-and-so study. 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.

14:31It's not like you have no autophagy, and then you cross a threshold, and now you have autophagy in a digital switch. It 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 millimole 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 you could really

15:03sort 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. Thank you for listening to today's sneak peek AMA episode of The Drive. If you're

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18:28So,