The Peter Attia Drive - #202 - Peter on nutrition, disease prevention, sleep, and more — looking back on the last 100 episodes

00:00:00.000 Hey, everyone. Welcome to the drive podcast. I'm your host, Peter Atiyah. This podcast,

00:00:15.480 my website, and my weekly newsletter all focus on the goal of translating the science of longevity

00:00:19.800 into something accessible for everyone. Our goal is to provide the best content in health

00:00:24.600 and wellness, full stop. And we've assembled a great team of analysts to make this happen.

00:00:28.880 If you enjoy this podcast, we've created a membership program that brings you far more

00:00:33.280 in-depth content. If you want to take your knowledge of this space to the next level,

00:00:36.820 at the end of this episode, I'll explain what those benefits are. Or if you want to learn more

00:00:41.320 now, head over to peteratiyahmd.com forward slash subscribe. Now, without further delay,

00:00:47.740 here's today's episode. Welcome to a special episode of the drive as we celebrate our recent

00:00:55.320 200th episode. To celebrate this milestone, we want to do something a little bit different,

00:01:00.620 which is something we did after our first hundred episodes. And that was a special episode called

00:01:05.720 Strong Convictions Loosely Held. The idea of this is to basically go back and look over topics that

00:01:11.720 were covered in the last hundred episodes, which is about two years, and talk about things where I've

00:01:16.720 changed my mind or taken a stronger viewpoint. So in this interview, I'm once again joined by Nick

00:01:22.480 Stenson. Due to the timing of this episode, it's going to be audio only. We are trying to get this

00:01:27.080 out on a very quick turnaround. So this is being recorded very shortly before it's going to be

00:01:33.300 released. In this episode, we talk about a number of topics. We talk about changes in my viewpoints

00:01:39.160 around things that deal with cancer, both in terms of screening and therapeutics. We talk about my evolved

00:01:45.240 thinking on atherosclerotic cardiovascular disease and around Alzheimer's disease genetics. In the topic of

00:01:52.040 nutrition, we get into some changes in my views around fasting and protein consumption. Talk a

00:01:57.780 little bit about psychedelics under the molecules heading. In exercise, we talk a lot about strength

00:02:04.240 training, cardio training, and I touch a little bit on my recent surgery and the implications of that,

00:02:10.500 although we're going to have a dedicated podcast on all things pertaining to that. Talk about sleep

00:02:15.800 and a supplement that I used to be very bullish on that has basically vanished, and then talk about

00:02:21.920 a drug that I'm very excited about right now. And let's see, what else do we talk about? I think we

00:02:27.860 then turn it over to a special discussion on all things Formula One. We do get a lot of questions

00:02:34.500 about Formula One, and I think that there's probably a relatively small but enthusiastic cohort of you

00:02:41.160 who have a lot of questions about F1. So we end on that deliberately so that those of you who are not

00:02:46.740 interested in F1 can tune out. But I think it's actually a pretty cool discussion, and I think even

00:02:51.040 people who are just casually becoming interested in F1 will find this interesting. So hopefully that's

00:02:56.180 more than six of you. So anyway, without further delay, please enjoy this episode celebrating 200

00:03:01.940 episodes of The Drive, and specifically looking back at the last 100.

00:03:11.220 All right, Peter, welcome to a special episode here. This is one you and Bob did way back for

00:03:20.160 episode 103, which is kind of this concept around strong convictions loosely held, which I'll have you

00:03:26.640 explain in a second. And we did this after the first 100 episodes of the podcast, and now we just

00:03:34.000 crossed episode 200. If we were a little better at planning, this would be episode 200, but episode

00:03:41.180 200 kind of... Maybe 201, technically, right? Maybe 201, but this kind of snuck up on us. So I think it's

00:03:46.800 going to be episode 202. So we're only off by one. This will be a little bit of a different episode in the

00:03:53.360 sense where it will kind of have an AMA feel to it, where I'll be asking you some questions, but it'll

00:03:58.300 be much more laid back. The prep that usually goes into a podcast didn't really go into this one,

00:04:05.620 because it's more so just asking you questions around looking back at the last 100 episodes,

00:04:11.500 episode 100 to 200. Where has your opinion changed? Where has it maybe gotten stronger? How has it evolved?

00:04:18.620 Which I think is really important for people to understand, because I think sometimes they can

00:04:24.000 listen to podcasts or hear people talk about things and just assume they can never change their

00:04:29.300 mind or assume it doesn't evolve. And so that's why I really like doing these. I think this will be a

00:04:34.520 good one for people. And then also for the small percentage of people who are interested, we do get a

00:04:39.760 lot of F1 questions. And at the end of this episode, we'll dedicate a little bit of that for all

00:04:46.240 those people who really want to dive into that. I'm cool with just doing this as a full F1 episode.

00:04:51.740 I guess for people, we're recording this on March 23rd. So we are now one race into the season.

00:04:59.580 And I have a lot of things I'm excited about. But I guess we'll refrain from that. And we'll just

00:05:04.520 make it a little F1 at the end. Yeah, a little bonus guy on there. So that will be good. But

00:05:10.280 why don't we just start off by just explaining this concept of strong convictions loosely held,

00:05:16.620 where it came from, your thoughts on it, and why you think it's so important, especially in

00:05:20.740 the science space, the health space, things of that nature.

00:05:25.520 It's a phrase that I'm sure many people have heard before. And I certainly wouldn't even know

00:05:29.920 where to attribute it to originally. But I can tell you where I attribute it to. I attribute it to

00:05:33.920 a friend of mine named John Griffin, who used to run a very successful hedge fund. And I just

00:05:39.120 remember, John, one day, we were sitting around talking about his investment philosophy. And I

00:05:45.320 just remember that expression coming up over and over again, which was, you have to invest based on

00:05:50.900 strong convictions, but they need to be loosely held. And so you have to constantly update your

00:05:55.580 assumptions with new information. And I thought, wow, that's, I mean, I can see why that makes sense

00:05:59.860 if you're going to be a good investor. Because if you invest in something based on a thesis,

00:06:03.820 but you can't readjust your thesis position based on new information. In other words,

00:06:08.840 if you're more interested in staying with a position, as opposed to evolving your position,

00:06:15.060 you're probably not going to be a very good investor. I realize, you know, that's kind of

00:06:19.380 the same in science medicine. And unfortunately, I think it's probably our default setting to dig our

00:06:24.800 heels in on a position. So ironically, I think it's viewed as a sign of weakness or being wishy-washy

00:06:32.280 when you change your mind. Certainly in politics, that's something that you get hammered for.

00:06:37.200 There's no sure way to get hammered in a political debate, it seems, than to have your opponent point

00:06:42.660 out where you have changed your positions. Someone who says, look, I used to be pro-choice,

00:06:48.720 now I'm pro-life, or I used to be pro-life and now I'm pro-choice, or I used to oppose same-sex

00:06:52.740 marriage and now I'm in favor of it. It seems like you're hosed in that position as opposed to

00:06:57.960 being able to explain why you've changed. And I understand the skepticism around politics.

00:07:01.720 It could also be that people in politics are just changing their minds because they're following the

00:07:06.180 political flavor of the day. But nevertheless, I think for what we do, it's important. And truthfully,

00:07:11.120 last point I'll say on this, this is a big reason as for why I'm not that excited about my book.

00:07:17.860 So I think people listening to this probably understand I'm in the final stages of trying

00:07:21.760 to finish a book. And this is a book that started in 2016. It's a book that's been basically rewritten

00:07:27.100 fully once. And it sort of occurred to me a couple of months ago that this is not a great idea. Now,

00:07:35.780 don't worry, I'm still going to do it, but it's not a great idea for the following reason.

00:07:39.120 Let's say I take my hands off the final manuscript in June of this year, and this thing gets published in

00:07:45.960 February or March of next year. I can promise you that there are things that I'm going to have changed

00:07:52.420 my mind on that will be in print just within that nine-month period, let alone in the years that

00:07:58.960 follow. So this is a form of communication where you're kind of locked into a point of view. You

00:08:06.040 don't get to really update print. So there are other reasons, right? I mean, a podcast will typically

00:08:10.460 reach more people than a book. We have more weekly podcast listeners than we probably have people who

00:08:14.780 are going to buy a book. So it seems to me there's very little upside for me in writing a book other

00:08:19.060 than maybe it's a good excuse to just put everything in one place that's easier to digest. But

00:08:24.380 nevertheless, what I love about a podcast is doing exactly what we're doing now, which is being able

00:08:29.560 to consolidate all the changes in how I think about stuff. I wasn't going to bring up the book, but now

00:08:35.460 that you did, I might as well ask a few questions on it that I'm sure people will be curious about. When

00:08:40.360 you talked about it previously, the draft was insanely long. This new manuscript, is it looking just as

00:08:47.700 long? Is it going to be a pretty hefty size or you think it's going to get cut down?

00:08:52.980 No, it's going to be cut down and we're already doing an amazing job of that. So we have a great

00:08:57.620 editor at Penguin Random House. And when we first connected, the manuscript was close to 200,000 words.

00:09:06.160 She thought, well, this really ought to be 80,000 words. I said, well, it's probably not going to be

00:09:10.580 that little, but I think we're both hoping that we can converge this thing to about 120,000 words.

00:09:15.420 That's still a pretty thick book, but I think that's manageable. And I think as Bill Gifford,

00:09:21.620 who's my coauthor, and I go through this, and we've been working really hard at this,

00:09:26.880 we're just relentlessly pushing each other. Like, how can this be said in fewer words? Is this point,

00:09:33.500 while interesting, necessarily relevant to the broader point we're making? If yes, keep it and

00:09:39.380 streamline it. If no, cut it. So you've probably heard me use the expression before, kill your babies.

00:09:44.200 This is the perfect example of killing your babies. For the folks listening who might not 1.00

00:09:49.520 know what that is, that was also great advice to me given when I was in medical school writing my

00:09:54.780 first scientific paper. I put so much work into it, and I had all of these figures and all of these

00:10:00.340 tables. One of the guys I was working with in the lab said, look, you've got to learn to kill your 0.88

00:10:03.860 babies. You're going to do 20 experiments that are not going to make their way into the paper, 0.88

00:10:09.380 and that's going to feel awkward. It's going to feel like, no, no, I need to show you as the reader

00:10:15.040 of this paper everything I've done and every experiment and every iteration. And similarly

00:10:20.940 with a book, there's a part of me that was like, I almost want the reader to be able to see how much

00:10:25.560 work has gone into this. But of course, that doesn't make for a good book. Nobody needs to sit

00:10:29.820 through a quarter of a million words, which is what this would easily be. So there's lots of baby

00:10:35.580 killing going on right now. I hope that that will make it better. And the only real big stress hanging

00:10:40.200 over my head right now is to do the audio book or not. I would strongly prefer not to do it. So

00:10:45.880 I'm sort of in the process of exploring who could be a good reader for the book too, so I could weasel

00:10:50.880 out of having to do it. Yeah, just because we're, this whole podcast is on looking back at episodes.

00:10:57.380 I think of the episode with Sebastian Younger, and there was some talk on there where he really

00:11:01.660 talked about how he refined his writing style and like the amount of work he would go into

00:11:06.600 to only say words that really mattered. It was really impressive. So I imagine that process, especially

00:11:13.840 when you're talking about such complex things is hard. And so I think I, like many people, will be

00:11:19.740 excited to read that when it comes out and just keep on keeping on and get that thing done.

00:11:25.760 Yeah, I have mixed feelings about it. I'm still probably in the state of not liking it very much.

00:11:30.600 It's, it seems very boring to me as I read it. I think, God, there's nothing new here. There's

00:11:35.960 nothing exciting here. And, but I think every author goes through that when they've read the

00:11:40.380 same thing 12 times. I just have to remind myself sometimes that for other people reading it will

00:11:46.540 offer something novel. Yeah, for sure. And for people listening, you know, if you have strong

00:11:51.920 opinions on if an audio book should be read by Peter, I know you put that poll on Twitter,

00:11:56.920 which was really interesting, but feel free to send us a message. Let us know how important you

00:12:02.120 think that is. And just so people understand, the reason I don't want to read it is there's

00:12:06.500 really twofold. One, a book of this duration will take two weeks to read. For me to take two weeks

00:12:11.900 off work is a really big deal, especially to do something I don't enjoy. Let's be clear. I mean,

00:12:18.140 I wouldn't enjoy this one bit. The second reason is I'm actually not a very good reader. So I think a lot

00:12:22.300 of people have this assumption because I do a podcast and I don't mind public speaking that I'm

00:12:25.580 a good speaker and I probably am. I'm actually a horrible reader. And I know this because I read

00:12:31.160 children's books to my kids every night and you'd think I'm an illiterate moron. Even my kids catch 0.99

00:12:37.240 the mistakes when I'm reading it. They're like, daddy, you missed that whole word or that sentence

00:12:40.680 or whatever. So I'm not a good reader, at least not an out loud reader. So this will be an especially

00:12:46.200 difficult challenge. I think there's a very good chance I won't add much value to the reading of the

00:12:51.660 book, even though I have a quote unquote familiar voice. Yeah. And you can be honest and say you

00:12:56.100 didn't accidentally miss those words. You were just trying to speed up bedtime and book reading

00:13:00.340 as any parent has done. You know, you just kind of skip a page when they're not looking. And

00:13:04.840 sometimes that book's a lot shorter than others. That's when we discovered that Reese was Rain Man,

00:13:10.320 which when he was about three and a half years old and he had a book on the water cycle.

00:13:16.280 This was the longest book ever. This was not a three-year-old kid's book. This was like a 13-year-old

00:13:21.140 kid book because it took 10 to 12 minutes to read this book, which anyone reading books to kids

00:13:27.480 knows that's a long book. And I basically would start skipping paragraphs. This was only after I'd

00:13:35.260 read the book four times to him in the span of, I don't know, two weeks. And he would recite the

00:13:41.140 paragraphs I'd missed. And that's when we knew there was something about that kid that was not

00:13:45.700 typical, to put it mildly. I actually have a video where I record him reading the entire book

00:13:52.520 without reading it. And he gets it almost verbatim. Well, I mean, maybe he's your guest

00:13:58.080 reader for the audio book. We just throw Reese in the booth and just let him go for a few weeks.

00:14:02.620 He has to memorize it. Someone's going to have to read it to him four times.

00:14:06.180 Bob Kaplan. We'll just send Bob out there. Just let those two go at it.

00:14:10.040 All right. Have we wasted enough time on this? Is anybody still listening? We'll make sure in the

00:14:14.780 show notes, we tell people that they can skip the first 15 minutes of this podcast.

00:14:19.400 So what we're going to do is we're just going to cover a few different themes and

00:14:22.440 larger themes, and then just talk about where your thoughts have maybe changed. So the first

00:14:27.420 theme is around diseases. So this can be anything from cardiovascular disease, cancer, Alzheimer's,

00:14:34.260 dementia, things of that nature. Anything that you think is really interesting there, or things that

00:14:40.760 you maybe change your mind on, or it's gotten sharper, kind of anything you want to say there?

00:14:46.180 Yeah, I'd say there were three things where my thinking today is either more clear, or just

00:14:53.360 frankly, more aggressive, different than it was before. So one is around cancer, and there are two

00:14:58.780 issues specifically. One is around ASCBD, atherosclerotic cardiovascular disease, and one is

00:15:05.000 around Alzheimer's disease. So I'll just take them in that order. So on cancer, there are two issues.

00:15:08.900 The first is around the promise of immunotherapy, and this really came out of the research that I

00:15:14.940 did to prepare for one of my favorite podcasts over the past couple of years, which is the podcast

00:15:19.900 with Steve Rosenberg. Folks haven't listened to that. I can't recommend that highly enough. And that

00:15:24.280 was something that was very personally exciting for me. Steve was probably the most important mentor

00:15:29.640 I've ever had professionally. And he's just not only one of the most remarkable scientists, but also one

00:15:37.000 of the most remarkable human beings. Even though I know the field of immunotherapy quite well, because

00:15:42.300 it's not something I'm in day in and day out, I did a lot of work to prepare for that podcast.

00:15:47.000 And we had a great discussion. And I think one of the things that came out of that,

00:15:50.360 that really blew my mind, was the fact that 80% of patients have neoantigens on their cancers that

00:16:01.460 are recognized by their immune system. I just want to explain why that's so significant for folks who

00:16:06.820 might not appreciate it. The holy grail of cancer therapy is undoubtedly immunotherapy. In other words,

00:16:13.900 anytime you can get the immune system to recognize your cancer as non-self, you're winning the game

00:16:21.200 because you get to use a cellular systemic system that could eradicate a tumor without the toxicity

00:16:29.700 and failures basically associated with systemic therapies like chemotherapy. Now, historically speaking,

00:16:36.860 very, very few people, meaning it's reportable in the literature, it's so rare, have a cancer where

00:16:45.120 the immune system can automatically recognize it at sufficient force to eradicate it. There are a

00:16:51.200 couple of such patients like that that Steve Rosenberg saw during his training that basically formed the

00:16:58.040 impetus for his life's work. Now, there's another subset of patients typically with cancers like

00:17:04.180 melanoma and renal cell cancer, which have a high mutagenic burden, where they might not have enough

00:17:09.840 immune cells to recognize and kill the cancer completely without any prompting, but if you

00:17:15.900 prompt them with a cytokine like interleukin-2 at a very high dose, that is sufficient for their T

00:17:22.960 cells to go and eradicate the cancer. To put that number in context, we're talking about 10 to 20% of

00:17:28.840 people with metastatic melanoma or renal cell cancer will respond to that. Again, these are patients who

00:17:34.060 would otherwise be dead in six months, and they would now go on to have durable remissions.

00:17:38.600 The next step would be using something called a checkpoint inhibitor. So these are drugs that

00:17:43.840 block the checkpoints on immune cells. These are basically the breaks on the immune system,

00:17:50.220 and by dropping these checkpoint inhibitors on patients, so things that block either CTLA-4 or PD-1

00:17:58.180 being the two most well-studied of these, we have the same effect. And this is an even broader subset

00:18:04.720 of patients, but again, it's still quite narrow in the grand scheme of things. And again, it tends to

00:18:11.040 only work in patients that either have specific mutations or patients that, again, have a very high

00:18:18.040 mutagenic burden, so people with mismatch repairs and things like that. But when you look at the fact

00:18:24.400 that 80% of patients, and everything I just talked about, the spontaneous remissions, the IL-2,

00:18:31.300 the checkpoint inhibitors might account for 10% of that 80. What about those other, call it 70% of

00:18:37.660 people? Well, I think what this finding gives us hope for is that we may, in fact, be able to use some

00:18:46.140 combination of tumor-infiltrating lymphocytes, TIL, or adaptive cell therapy where you genetically engineer

00:18:52.400 T cells with that recognition. And so the reason that those patients aren't having spontaneous

00:18:58.880 remissions or aren't responding to interleukin-2 or even checkpoint inhibitors is because they probably

00:19:03.600 don't have enough of those T cells yet. So this now becomes just as much a bioengineering problem

00:19:11.300 as it is an immunology problem. You have to be able to recognize those cells. Well, it turns out that's

00:19:16.680 pretty easy to do. And now you have to be able to expand them in a manner where they still have the

00:19:21.660 longevity necessary to go in and be infused into patients and basically arrest and eradicate their

00:19:28.980 tumors. So all of this is a long way of saying, I really think that in 10 years, we're going to

00:19:35.640 basically be using designer-based immunotherapies to eradicate most solid organ metastatic cancers.

00:19:43.640 That's a bold-ass statement. Let's call a spade a spade. But the reason I think this is so doable

00:19:48.500 is historically, it's the impediment to this, and then where people I think would say today there's

00:19:55.320 an impediment to this, is cost. If every single person has to have their own T cell or adoptive

00:20:02.580 cell therapy regimen created, well, I mean, that's obviously very costly, right? That could be a couple

00:20:09.900 hundred thousand dollars to generate. But the reality of it is when you look at the cost of cancer

00:20:14.500 therapeutics today and the failure rate, I actually think the cost of doing this is less, especially

00:20:21.360 when you do it on a quali basis, so a quality adjusted life year basis. Because today it's not

00:20:27.560 uncommon to spend $80,000 on a treatment that extends life by four months. Well, would you rather

00:20:35.000 spend $80,000 on something that's going to extend life four months or $300,000 on something that's going

00:20:40.020 to extend life indefinitely with respect to cancer? So to me, it's just going to require kind of a

00:20:45.880 fundamental shift in how we do the actuarial science around durable remission therapies. So

00:20:52.280 that's on the cancer front, something I'm very excited about. Let me follow up a few questions there,

00:20:58.240 because I think you'd kind of make some big statements. And I think there was a few terminology

00:21:02.520 that it would be helpful to let people know what they are. So one is you mentioned solid organ

00:21:08.280 cancers. So maybe just run through what those are. The other is you mentioned metastatic cancer.

00:21:14.300 So maybe just define what that is, because I think that will be helpful. The other thing I was going

00:21:18.540 to say is for those wondering, the episode with Steve Rosenberg is number 177. And it's also a

00:21:25.080 amazing episode of someone who just never gave up and just was so hyper-focused. If anyone hasn't

00:21:32.780 listened to it, it's very technical, but the stories he tells and the stuff he was able to do is

00:21:38.060 very, very impressive. Yeah. So let me go back and answer those two points. So what does

00:21:43.860 metastatic mean? Metastatic means the ability of the cancer cells to spread beyond their primary

00:21:49.640 site of origin. And that's one of the two hallmarks of a cancer cell. So one of the two things that

00:21:55.600 defines a cancer cell and differentiates it from a normal cell. So if you have somebody with colon

00:22:00.600 cancer, what is it about the colon cancer cells that is different from the regular colon cells

00:22:07.720 One of them is this ability to leave the colon and go someplace else. So colon cancer cells could

00:22:14.400 now grow in the liver, whereas regular colon cells, if you put them in the liver, wouldn't grow.

00:22:20.060 The second thing is basically the inability to respond to cell cycle signaling. A regular

00:22:27.580 cell from the colon will respond to signals that tell it to stop growing. That's how it knows

00:22:33.120 to stop. So if you have an injury to the colon, it will respond appropriately and grow to heal,

00:22:39.920 but then it will stop growing once it's told, Hey, we're done. We don't need you to grow anymore.

00:22:44.180 That's fine. Colon cancer cells won't do that. Those are the two hallmarks is not responding to

00:22:48.320 growth signal stopping and being able to spread to your first question. What does a solid organ tumor

00:22:53.620 mean? Yeah. So it's basically anything that is not a leukemia and lymphoma effectively. So leukemias and

00:22:59.280 lymphomas probably account for about 20% of cancers and then the solid organs about 80%. That's really

00:23:06.600 cancer deaths, I should say, not just cancers. So almost every time we hear about somebody dying of

00:23:12.720 cancer, we're usually hearing people, someone dies of colon cancer, breast cancer, prostate cancer,

00:23:17.020 brain cancer. Those are what we call epithelial tumors to be more technically correct.

00:23:21.760 And you mentioned the timeline 10 years. Is that timeline where this becomes a possibility or is

00:23:32.640 that the timeline where it becomes widely available to the mass public? Are those the same or would

00:23:38.400 they be a little different? No, they'd be different. I think 10 years might be aggressive

00:23:42.260 for this to be the standard of care, but I think 10 years would be the time when it's going to be out

00:23:48.400 of clinical trials and something that's going to be available at least to some. My guess is

00:23:54.280 unfortunately in 10 years, I mean, again, I'm just making this up. It might not be something that is

00:23:58.960 covered by insurance, which would then immediately limit to a fraction of the population that people

00:24:03.340 that could get this, but it's going to have to get some traction beyond clinical trials. And there

00:24:10.180 might be a period of time before this is covered. Again, I could be wrong. It could go straight from very

00:24:16.120 successful clinical trials directly to something that Medicare reimburses for, but that's what has

00:24:22.140 to happen, right? I mean, unless Medicare and Medicaid reimburse for this type of treatment,

00:24:26.940 it could never be widespread regardless of how successful it is. Got it. All right. Continue on

00:24:32.440 with the second piece under cancer. Yeah. So the second thing on cancer is just my complete aggression

00:24:39.300 when it comes to screening for gastrointestinal cancers. Let's just kind of put big, big things in

00:24:45.560 perspective. How many cancer deaths do we have each year? So I think for 2020, we're looking at

00:24:53.700 probably 600,000 people in the U.S. died of cancer. And how many of those were in the digestive system?

00:25:02.400 170,000 of the 600,000. So the GI system is a really big issue, right? And that's basically everything

00:25:10.460 from mouth to anus. Now, some of those things are very difficult to screen for. So pancreatic cancer,

00:25:17.640 we don't really have a great way to screen for it. And that's why we use things like diffusion

00:25:23.000 weighted image, MRIs, liquid biopsies as ways to basically pursue those things. Now we have a podcast

00:25:31.740 that's coming up on liquid biopsies and all things around that. So that's going to be a very interesting

00:25:36.900 podcast. We had a previous podcast that was probably in the first hundred with Raj Atarwala,

00:25:42.900 where we talked about diffusion weighted imaging MRI for cancer screening. So if we put those things

00:25:47.980 aside, the good news is that there are a lot of cancers for which we can directly take a look at

00:25:55.960 the epithelial surface that is going to become cancerous. And there is no part of that that is

00:26:02.380 more important than the colon. So the esophagus, the stomach, and the colon probably represent,

00:26:12.120 I don't know, 40% of those GI cancers. So again, liver and intrahepatic bile duct and pancreas are

00:26:23.620 probably also about 40%, and those are much harder to screen. But when you look at organ-specific

00:26:29.260 sites, colon cancer is generally in the top three leading causes of death for both men and women.

00:26:38.140 And what I'm about to say is going to sound incredibly bold and controversial. It seems

00:26:43.480 increasingly true to me, which is nobody should ever die from colon cancer. And I would add the

00:26:49.020 same for esophageal and stomach. And the reason for that is, especially in colon, the progression

00:26:56.180 from non-cancer to cancer is visible to the naked eye through the transition of non-malignant polyp

00:27:05.480 to malignant polyp. So if you did this as a thought experiment, if you did a colonoscopy on somebody

00:27:12.240 every single day of their life, they would never get colon cancer because at some point you would see

00:27:18.060 the polyp, you would remove it while it is non-cancerous, and they would not get cancer.

00:27:22.300 So of course, how do you turn that thought experiment into a real-life idea? Well, you have

00:27:27.900 to ask the question, what is the shortest interval of time for which a person can have a completely

00:27:35.200 normal colonoscopy until they can have a cancer? There's no clear answer to this question, and

00:27:41.500 we've done a lot of work on it, and I've spoken with a lot of gastroenterologists about it, and there

00:27:45.640 are certainly some case reports that it can happen in as little as six to eight months. Of course,

00:27:50.980 one has to question whether, in fact, people had perfectly normal colonoscopies six to eight

00:27:57.800 months earlier, and it's possible that they did not and that something was actually missed at the

00:28:02.620 time. But I think most people would agree that if you had a colonoscopy every one to two years,

00:28:09.780 the likelihood that you could ever develop a colon cancer, while maybe not zero, is so remote

00:28:17.460 that you could effectively take colon cancer off the list of the top 10 reasons why someone dies

00:28:24.500 of cancer. And so it's for that reason that I'm very aggressive when it comes to this type of

00:28:31.180 screening, which also includes upper endoscopy. So you basically get for free the esophagus and

00:28:36.340 stomach when you look at the entire colon, rectum, anus. And what are your costs? Well, your costs are

00:28:43.340 obviously the dollar cost, which is not cheap. I can't tell you what the average cost of a

00:28:47.820 colonoscopy. I think when I get them done, because I'm getting them done outside of regular screening,

00:28:53.260 so I'm paying for them. They're certainly not cheap. I want to say maybe I'm paying $2,000 for

00:28:57.840 a colonoscopy, so that's a huge cost. And then there's obviously the risk of the sedation, which

00:29:02.460 again is not zero. In the hands of someone who's doing this every minute of every day, it's very small.

00:29:08.740 And then of course there's the risk of perforation, which again is also incredibly small, especially

00:29:14.360 in a healthy individual. And even if it does happen, it's generally something that's pretty

00:29:18.840 easy to manage. So again, is this something that I'm taking lightly? No, it's not. And I can't tell

00:29:24.080 you yet what the ideal frequency is, because at some point, for example, a colonoscopy every day

00:29:28.760 would be a silly idea on all of those metrics, right? Your risk of complication is clearly going to

00:29:34.580 exceed your risk of cancer, notwithstanding the cost and daily challenges of bowel preps.

00:29:40.360 So where is that number? I don't know, but it's much more frequently than what's being done today.

00:29:45.780 That's what I would propose. It's not every five to 10 years. So it's probably every one to three

00:29:50.740 years would be my intuition. I think the other thing there, and to follow up Raj's episode is episode 61.

00:29:57.840 And another good resource on this is after Chadwick Boseman passed away, we did a weekly email on it,

00:30:05.900 and we'll link to it in the show notes. It's called colorectal cancer screening. And I think the other

00:30:11.000 thing that was talked about in there, which you do a little different, is not only the frequency,

00:30:15.580 but the age in which you start your patients for their first colonoscopy. I think the standard is

00:30:23.340 50 or 45 now, but either way you prefer much earlier. I think they are moving it down. I mean,

00:30:30.160 in our practice, we think 40 is the age at which a person should have their first colonoscopy if they

00:30:34.860 have no history of colon cancer. About when I had my first one was 40 or 41. I'm 49 right now,

00:30:42.960 and I'm scheduled for a colonoscopy in a month, and that'll probably be my fourth one. And to be clear,

00:30:49.740 this requires me arguing a little bit with my primary care physician, who's saying, Peter, 0.99

00:30:54.560 you're being a bit ridiculous. But then I say, look, I want you to go and read what I've written 0.85

00:30:58.140 about this. Let's hop on a call and let's discuss this. In the end, he's like, okay. And then you

00:31:03.280 could argue, well, maybe I get my way because I'm a doctor and I can be more persuasive in my arguments.

00:31:07.420 But I think these are the discussions patients need to be having with their doctors if they're in a

00:31:11.760 position that they can afford to do this outside of the regular screening. And if not, I think they

00:31:16.340 should push to see whatever can be done with inside the bounds of their insurance as well.

00:31:20.760 I realize that we're all tainted by our biases, but the images of the people that I have seen

00:31:27.680 who have had colon cancer before the age of 50, I mean, those are seared into my brain.

00:31:33.680 And that's why I think those are just such asymmetric benefits.

00:31:38.260 Yeah, definitely. Okay. So I think that was the two things on cancer. I think you had a few other

00:31:43.240 things in diseases that you mentioned early on. Yeah. So on ASCVD, I've also become far more

00:31:50.340 aggressive on the timing and magnitude of ApoB reduction. So take a step back and ask, what are

00:31:59.560 the leading causes or modifiable causes of ASCVD? The big three are pretty unambiguously smoking,

00:32:10.060 hypertension, and hyperbeta lipoproteinemia, which is just a really fancy word for saying

00:32:16.060 too many lipoproteins that have ApoB on them. So that's LDL, IDL, VLDL, LP little a. By measuring

00:32:25.460 ApoB, why I'm such a fan of measuring ApoB, as opposed to just measuring LP, LDL particle number,

00:32:32.580 or LDL cholesterol number, is we have one single number that captures the total concentration of ApoB.

00:32:39.520 And while that's pretty well associated with non-HDL cholesterol, which is a far better

00:32:44.500 surrogate than LDL cholesterol, it's still better. And that's been demonstrated. And I think we even

00:32:50.220 covered that in a previous podcast where we went over the discordance between non-HDL cholesterol

00:32:56.380 and ApoB. So now the question becomes, well, when should you start ApoB reduction and how much

00:33:03.340 should you lower it? And I'll tell you, I used to take a point of view that if a 40-year-old

00:33:09.040 had an elevated ApoB, let's just put some numbers to this, right? So the 20th percentile

00:33:15.520 of ApoB is about 80 milligrams per deciliter. I used to say that, let's say somebody was at the

00:33:22.880 50th percentile, they're 40 years old, their calcium score is zero, and they were ambivalent

00:33:28.760 about lipid lowering therapy. And let's assume that they're not insulin resistant and you've

00:33:33.560 done all of the things that you can do reasonably with nutrition. I wouldn't push that hard.

00:33:38.640 I've now taken a very different stand, which is I've basically taken the stand with others

00:33:42.420 that I've taken with myself, which is the evidence is overwhelming that infantile levels

00:33:49.760 of ApoB are not deleterious in any way. Meaning an ApoB of 30 to 40 milligrams per deciliter,

00:33:58.020 which is the level that children would have, poses not only no risk to children as evidenced

00:34:02.700 by the fact that, I mean, that doesn't require an explanation, but as evidenced by what we see

00:34:08.960 in the literature on adults with levels that have been pharmacologically reduced, tells me that we

00:34:14.800 need to be lower. And the amount of time it takes to see a benefit tells me we don't want to wait

00:34:20.820 until there's an issue. In other words, if the reason we begin therapy is because somebody has

00:34:26.960 a positive calcium score, which again, we covered this in great detail in, does that AMA come out yet?

00:34:33.280 I was just going to say that AMA will be released two weeks after this.

00:34:37.280 Oh, okay. Okay.

00:34:37.840 Yeah. So for people listening, we have a dedicated ASCVD AMA, which goes into heavy detail for about

00:34:46.080 90 minutes on all this stuff, where if this is of interest, hang on for a few weeks and we'll be

00:34:52.160 diving even deeper into it. Yeah. I get a bit lost with the recording cycle, but that's a great AMA

00:34:57.400 that goes super deep on basically all of the reasons why I think my point of view now is treat early

00:35:04.660 and treat aggressively. And I will now also make a very bold statement. Again, let's start with the

00:35:10.280 thought experiment, right? If the thought experiment for colon cancer was do a colonoscopy every day on

00:35:16.980 a person's life, starting at the age of 30, would you eliminate colon cancer deaths? I think the answer

00:35:23.080 is yes. And similarly, I would say pharmacologically lower ApoB to somewhere in the 20 to 30 milligram per

00:35:32.640 deciliter range for everybody in the population while someone is in their 20s. Can you eliminate

00:35:39.420 ASCVD? And I think the answer is probably yes. In other words, I think what you're basically going

00:35:44.920 to do is eliminate death from atherosclerotic causes. And that would need to be started in the

00:35:52.240 20s? I think so. Yeah. Very early on. Yeah. So again, how do you take that thought experiment and

00:35:57.900 turn it into a practical implication? Because I don't think it's practical to take every 20-year-old

00:36:03.460 and obliterate their ApoB. Although it's clearly something we do in the subset of patients who have

00:36:10.940 significant genetic abnormalities, such as the cluster of genetic abnormalities that coalesce

00:36:17.520 around a condition called familial hypercholesterolemia. We certainly do medicate those patients,

00:36:22.320 usually as teenagers. So this is not some completely crazy idea. But I think practically

00:36:28.180 what it means is basically by the time you're in your late 30s or early 40s, if you have any measure

00:36:34.020 of ApoB that's even north of the 20th percentile, that should be completely lowered. So in some ways,

00:36:41.760 I would view an ApoB ceiling of 60 as the limit. And that's probably at about the fifth percentile.

00:36:48.280 Now, you'd sort of want everybody to be below the fifth percentile.

00:36:53.540 Yeah, just because I think a lot of people listening, they might know their ApoB number. And

00:36:58.000 I'll also say if anyone can't wait two weeks for that AMA, episode 185 with Alan Snyderman was just

00:37:04.420 an amazing episode and talking about not only ApoB, but just how you think about risk. Do you know the

00:37:10.300 rough numbers of 20 percent, 50 percent, and 80 percent ApoB just for people who maybe have their ApoB

00:37:18.180 metrics down, but they don't know where it relates in the percentage?

00:37:22.820 Yeah. So fifth percentile from the Framingham offspring study was 62. I just, in my mind,

00:37:28.300 keep 60. 10th percentile is about 70. 20th percentile is 78. So I just think of 80. 50th percentile

00:37:36.340 is about 100. It's technically 97. 80th percentile, 118. So I just kind of think of 120.

00:37:44.020 95th percentile is 140. Yeah. I mean, we're going to see patients of all these levels. I've got a

00:37:48.980 new patient whose first labs I'm reviewing very soon. I just got his labs back the other day.

00:37:55.100 His ApoB is, I don't know, I want to say like 171. And the 95th percentile is 140. So he's,

00:38:01.520 you know, in the 99.9th percentile, he almost meets diagnostic criteria for FH based on his

00:38:08.040 LDL cholesterol. But you're going to see the whole spectrum here. But again, going back to this point,

00:38:13.660 I just don't see a reason to have an ApoB ever north of 60 milligrams per deciliter.

00:38:20.000 And I think when you look at a lot of the Mendelian randomizations, plus the clinical trial data,

00:38:24.620 if you have an LDL cholesterol below 30 or an ApoB below 40 milligrams per deciliter

00:38:35.100 for a very long period of time, I think the odds that you're going to suffer ASCVD are incredibly

00:38:42.620 low. Again, the earlier you start and the lower you go, the more you can make that number approximate

00:38:47.360 zero. And therefore, it then only becomes a question of what are your therapeutic choices

00:38:51.940 to get there? How do you do this in a way that minimizes the side effects of that? Because for

00:38:56.720 some people to lower ApoB that much is trivial. Like in me, it's actually really easy. I take a

00:39:03.260 PCSK9 inhibitor and I take a statin and I can basically eradicate it. And I don't have any issues

00:39:09.280 with either of those. But for some people, statins are difficult to tolerate. About 5% of the population

00:39:14.720 has intractable muscle soreness. And that appears to be the case regardless of which statin you use.

00:39:20.420 And we tend to rotate through different statins. I like to start with resuvastatin or pravastatin.

00:39:25.600 And then if we have difficulties there, move to patavastatin or livalo. But if people can't

00:39:31.400 tolerate any of those things, today we have so many other options. If they're a hyperabsorber,

00:39:35.920 we would use ezetimibe. If they're a hypersynthesizer but can't respond to statins,

00:39:40.620 we use mapendoic acid. So we have lots of tools up our sleeve today, more than ever before. And that's

00:39:46.460 why I just think we should be more and more aggressive on this now.

00:39:49.780 Yeah. I mean, you could say it's even a more bold statement too, because listening to that

00:39:54.560 Alan Snyderman podcast and just how many doctors, especially in the US, don't even look at ApoB.

00:39:59.980 So the importance for people listening to this too is when they go to their doctor and they're

00:40:03.920 going to run their labs, just making sure to bring up, is it possible to get an ApoB ran? Because

00:40:08.840 if they just do what a typical cholesterol panel or a typical annual exam, it might not even be looked

00:40:14.840 at. Yep. Anything else on diseases that we want to cover before we go to our next subject?

00:40:21.480 One last little thing I'll just say, and this will probably come up in a dedicated podcast down the

00:40:26.140 line because there's just been so much interesting stuff going on. But I think when it comes to

00:40:30.100 Alzheimer's disease, our focus now on genes outside of ApoE is pretty significant.

00:40:37.740 I don't think Richard and I have ever spoken about this on a podcast, Richard Isaacson,

00:40:42.280 but it's probably something we need to revisit. We're working on a paper right now that we'll get

00:40:47.600 into some of this stuff, but it turns out that there are a lot of genes that seem to modify the

00:40:52.620 risk of ApoE. So anybody listening to this who's been regular listening to the podcast is undoubtedly

00:40:59.340 familiar with ApoE and it's three subtypes, type two, three, and four. And of course you get two of

00:41:06.960 each, you get two genes. So you can have the six possible combinations there. The fourth isoform of

00:41:13.660 that is the high risk one. So if you're a 2-4, it seems to more or less be a wash, maybe slight

00:41:19.900 increase in risk. The 3-4 seems to be associated with about a two to three fold risk in Alzheimer's

00:41:25.820 disease. And the 4-4, probably about an eight to 12 fold or maybe eight to 10 fold increase in risk. 0.97

00:41:31.300 But we also know at the individual level that even though everything I just said is true at the

00:41:36.540 population level, it doesn't explain what happens at the individual level because there are some

00:41:40.560 individuals who walk around with 4-4s who don't seem to get Alzheimer's disease. Or if they do,

00:41:46.880 they get it very late in life and it's indistinguishable from the sort of population

00:41:50.980 variant. So they're not getting this variant where they're being taken over by this disease at the age of

00:41:57.240 61 or something horrible like that. It turns out that there are a bunch of other genes that we're

00:42:01.860 now starting to understand modify the risk of E4. Some things make it more significant, some things

00:42:09.520 make it less. So there are certain haplotypes of the TOM40 gene that amplify risk. There are certain

00:42:17.980 mitochondrial haplotypes that amplify risk. One of the most exciting genes is the clotho modifier. I think

00:42:26.040 it's KLVS is the modified snip of clotho that actually seems to erase all of the downside of

00:42:33.560 APOE4. So APOE4 people who have this clotho subtype have baseline risk. So one other thing that I'm now

00:42:44.440 becoming really interested in, unfortunately, the ways to measure these other genes, it's very challenging

00:42:51.120 and we have to do it by brute force today. So we don't yet have a standardized way to do this. So it

00:42:57.020 takes a lot of time and costs a lot of money to take a whole genome sequence and do the search for

00:43:03.680 all of these other subtypes. It takes months. A big step in the right direction here is going to be

00:43:09.560 getting more data and getting those data for less than $20,000 per person.

00:43:15.220 Yeah. That was going to be my follow-up question is how does someone go about

00:43:18.760 getting those genes tested? Do you have a rough timeline in when that might be more widely available

00:43:25.580 or even less cost prohibitive? Is that years down the road? Is that 10 years longer?

00:43:31.580 It should be sooner. You know, this is a solvable problem. I think this is just about throwing enough

00:43:35.860 dollars at it. And a lot of our patients have actually expressed an interest in this. And

00:43:40.280 a few of them are actually kind of working with Richard Isaacson on ways to potentially speed this

00:43:45.260 up and streamline how it's done. But unfortunately at this moment in time, whenever we do this,

00:43:52.180 it is a brute force labor intensive exercise that again, we have the technical chops to be able to

00:43:59.880 do if we can streamline. All right. So moving to our next category, which longtime listeners will know

00:44:07.560 is your absolute favorite thing to talk about. Um, if we had a choice, you would talk about this every

00:44:13.080 week and we have to usually talk you off the ledge of not doing another nutrition podcast. So anything

00:44:19.840 on nutrition that you specifically want to bring up or talk about? Yeah, I think there were two things

00:44:26.140 on the nutrition front that are worth talking about where I've become more pointed in my feelings over

00:44:32.140 the past roughly two years, which I guess would be over the last hundred episodes.

00:44:35.660 So the first is my view that I think most of the benefit of time restricted feeding

00:44:42.820 is accrued through caloric restriction. So I've always been a little unsure of how much of the

00:44:51.640 time restriction was exerting its benefit through factors that go beyond what is likely a reduced

00:44:58.740 calorie intake in someone with a smaller feeding window. So in other words, was there something

00:45:02.500 magical about not eating? So if you had an experiment that was done where people are going

00:45:07.940 to eat 3000 calories a day spread out over the course of 12 hours versus people that are going

00:45:12.720 to eat 3000 calories spread out over six hours, is there any difference between them? And I think

00:45:17.240 the answer today is no. I think the answer is nope. When people talk about how time restricted

00:45:23.080 feeding is helping them lose weight and manage insulin resistance and things like that,

00:45:27.620 I think it appears that that's all due to reduced caloric intake. It's just harder to eat more

00:45:33.460 during a narrower window. And at some point that window gets narrow enough that it's almost impossible

00:45:37.880 to eat as much as you would in the course of a day, unless you're deliberately being as gluttonous

00:45:43.200 as possible. And I've seen people attempt to do that for reasons I don't understand.

00:45:46.460 And I think where this gets problematic is in people who can't really afford to lose too much muscle

00:45:55.720 and not completely atypical TRF scenario I see is in a patient who becomes completely obsessed with

00:46:05.080 only eating in a six hour window or even less. And at the end of a year, they've lost five pounds.

00:46:13.780 So they were kind of normal-ish weight to begin with. You know, they were 180 pounds to begin with

00:46:18.540 and they're 5'11", pretty normal. And a year later, they're 175 and they're like, this is just amazing.

00:46:25.360 I've lost five pounds. I feel like I can eat whatever I want. Then you do a DEXA scan on them and you

00:46:30.720 realize, well, you lost 10 pounds of lean tissue and you gained five pounds of fat mass. So yes,

00:46:40.120 you're down five pounds, but your body fat is actually up. I'm making this up because I'd have

00:46:46.600 to do the math, but your body fat's up 3%. Your visceral fat is up by 500 grams. Nothing has moved

00:46:54.260 in the right direction except this very, very crude measurement of the number on the scale.

00:46:59.880 In these individuals, I think because they're eating so much less protein, they're impairing muscle

00:47:06.560 protein synthesis. So they're actually losing lean mass even while putting on fat mass.

00:47:12.220 They're oftentimes becoming insulin resistant. I especially see this in people who are doing

00:47:16.640 one meal a day, the so-called OMAD, especially because most people who are doing that are doing

00:47:22.420 it late in the day. And so now they're having impaired glucose homeostasis overnight. We're seeing

00:47:29.800 high glucose levels overnight, probably high cortisol levels and impaired glucose tolerance in the morning.

00:47:34.860 So a lot of these things just aren't what we would want to see. Now, there are some people for whom

00:47:41.660 that still works well. So I've also seen people who lose a hundred pounds and 70 of it is fat and 30 of

00:47:53.100 it is lean and they're net better off because they were starting at a body weight of 300 pounds and they

00:48:00.800 certainly had the amount of lean mass to improve. So their body fat maybe goes from 50% to 35%. I'm

00:48:08.400 kind of making those numbers up. So they're moving in the right direction. The point here is, I think

00:48:13.500 you need to ask yourself before you go on an aggressive TRF regimen, how much muscle mass can

00:48:19.800 you afford to lose? And if the answer is none, which is, it should be the answer for most people,

00:48:24.300 by the way, most of us don't have the freedom to lose any lean mass. Then you got to make sure

00:48:30.560 you're not restricting protein and that you're thinking about when you can refuel in relation to

00:48:37.520 exercise. So Peter, when people listening are kind of trying to figure out, okay, how much muscle do

00:48:45.360 they have? Can they get a baseline? And then if they are doing various diets or time-restricted

00:48:51.320 feeding, things of that nature, and they want to see what actually went up and down, what's the best

00:48:57.560 way for them to do it? Is it a DEXA scan? Is there another way outside of that where they can test this?

00:49:03.520 I think DEXA is the only way to do it, truthfully. I mean, obviously it's not the single most accurate

00:49:08.040 way to do it. There are more accurate ways to do them, but those would all be done in a research setting.

00:49:12.460 DEXA is relatively inexpensive, a hundred dollars in most places. Maybe if you're in a place like

00:49:19.300 New York, it's more, but we're talking of something in the low hundreds of dollars, not something that

00:49:25.300 is thousands of dollars. And the information it yields is also segmental, which is really valuable.

00:49:32.700 So unlike the sort of buoyancy-based tests, which I think are quite inaccurate anyway,

00:49:38.660 you don't get the segmental information. You don't get the information of visceral adipose tissue. So

00:49:43.920 when we do a DEXA scan, we're looking at lots of information. We're looking at BMD, bone mineral

00:49:50.620 density, total body fat, things like that. But what I'm really interested in is what's your fat-free

00:49:56.220 mass index. So that's the total lean tissue in kilograms divided by height in meters squared.

00:50:02.680 The ALMI, which is the appendicular lean mass index, which is the same as the FFMI,

00:50:07.880 except it's only using the lean mass of the four limbs, not including the torso. We're looking at

00:50:13.460 VAT, and we're putting all of these things on a nomogram to see where you rank for your age and sex.

00:50:20.380 And that's where I think people need to be really focused. And frankly, I care much more about those

00:50:24.620 metrics than I care about your total body fat percent. If your body fat percent is at the 40th

00:50:31.700 percentile, but your ALMI, FFMI are at the 90th percentile and your VAT is at the 10th percentile,

00:50:39.900 I mean, that's perfectly adequate. And again, a lot of that total body fat in some ways comes down

00:50:45.260 to a little bit of vanity once the biomarkers are themselves also great.

00:50:50.960 Yeah, I think that was one of the most interesting things. We had an internal meeting about this other

00:50:55.320 day, which is just, it surprised me how cheap a DEXA scan is. And if people just search the city they're in

00:51:02.380 in DEXA, I think they'd be surprised to find that out. And then same thing with VO2. And I know we'll talk

00:51:07.640 about an exercise here, but some of the places that do DEXA scans can also do VO2 max tests. And so it's

00:51:15.080 something that if people haven't done it, it's worth looking into and making that investment in because of

00:51:20.740 what you can learn from there. The other thing as you were talking that I thought of was, and we'll

00:51:25.600 have to link it in the show notes, is maybe one of the greatest commercials ever made, which is the

00:51:30.720 Taco Bell protein commercial and just the overall importance of protein. Before we move on, is there

00:51:39.720 anything else in nutrition you want to touch on? I think on the topic of protein, we're probably

00:51:45.720 underdoing it for most people. I don't think I was paying enough attention to it. And I think the RDAs,

00:51:52.980 the recommended daily allowances are kind of out to lunch. You know, the RDA for protein is something

00:51:59.160 to the tune of, I want to say it's like 0.8 grams per kilogram of body weight or something pathetic like 0.92

00:52:06.360 that. You take an 80 kilogram person, so someone weighs like about a buck 75, and that person should 0.65

00:52:12.620 only be eating 65 grams of protein a day or something asinine, like 0.8 to 1. And the reality

00:52:18.500 of it is, I think the RDA is predicated on how much protein you need to like live versus how much

00:52:25.620 protein you need to thrive. And so I think when you look at those data, you realize it's probably closer

00:52:32.460 to two grams per kilogram or about a gram per pound of body weight. And that quote unquote toxicity of too

00:52:41.260 much protein toxicity is that? Well, it's generally kidney toxicity. If you consume enough protein,

00:52:47.480 you're going to overtax the kidneys because that's how we excrete the excess nitrogen. And you're looking

00:52:53.160 at some more in the order of three to four grams per kilogram before you get into the places where

00:53:00.680 you're going to start to challenge your kidneys' abilities to take care of excess nitrogen. So this is

00:53:05.960 something that we're also becoming much more attuned to in our patients. It seems to be a really big

00:53:12.100 problem in middle-aged women. That's where we're probably seeing the biggest deficits are these 1.00

00:53:18.280 women that show up with no muscle mass, eating no protein, doing very little strength training. I mean, 1.00

00:53:25.900 to me, that is a recipe for a shorter life, but more importantly, a lower quality of life.

00:53:32.280 Not to keep plugging future episodes, because I think what people may not realize is at any time

00:53:38.580 of the year, we have about 12 unreleased episodes. So we kind of bank episodes and just because of the

00:53:46.540 nature and we do them and releasing them once a week, there's a lot that are unreleased, but a few

00:53:51.880 weeks after this, so in late April, there's a follow-up conversation that you and Lane Norton had,

00:53:57.000 which kind of gets into a lot of this, even in more detail. Everything from the time-restricted

00:54:04.160 feeding to protein and even you both get in a conversation around what Lane would do and how

00:54:11.120 he would prescribe a workout routine, protein routine for that person, the roughly 50-year-old

00:54:17.440 woman who does cardio, doesn't do a lot of strength training, but needs to build in muscle. So 1.00

00:54:22.340 if people want to hang on for a few more weeks too, that's coming in more detail. I think it makes

00:54:28.020 sense then to kind of go a little bit on the path we're going, which is exercise. So I don't want to

00:54:35.040 say there's a lot of things that changed with your view on exercise because you've always been

00:54:39.400 a big proponent of it, but from how I've even heard you talk about it, it seems you're more sold

00:54:46.440 than you've ever been on the importance of exercise in someone's longevity. So do you want to maybe talk

00:54:54.480 about just the theme of exercise and where you've evolved, what your thinking is now, and why you've

00:55:00.720 even put more of an emphasis than before? Yeah, you're right. It seems odd that I would even be

00:55:06.660 talking about this given that exercise has always been such an important part of my life personally,

00:55:11.860 but I think I've now come to appreciate the magnitude of the value that is brought to a

00:55:21.680 person's lifespan and healthspan by having higher cardiorespiratory fitness and more strength.

00:55:28.280 And you can't really get more strength without training. So more strength is synonymous with

00:55:32.660 training, with strength training, obviously. I think I posted something on this a long time ago,

00:55:37.840 or not that long ago, maybe a month or so ago on Instagram and Twitter, where I kind of walk

00:55:42.520 through some of the data on this. We'll link to that. But the gist of it is when you look at the

00:55:48.340 improvements in all-cause mortality by moving up the chain of cardiorespiratory fitness, so moving from

00:55:57.940 being in the bottom 25th percentile to the 25th to 50th percentile, they have terminology for all of

00:56:05.640 those things like low, below average, above average, high, and elite, which would be sort of bottom 25th

00:56:11.780 percentile, 25th to 50th, 50th to 75th, 75th to like 97.5, and then the top, call it 2, 2.5%.

00:56:19.160 As you march up those strata, your all-cause mortality drops. And it drops at levels that

00:56:29.400 aren't appreciated by any other intervention. Quitting smoking, going from having end-stage

00:56:36.380 renal disease to not, and it's easier to look at these in reverse. So comparing someone with

00:56:40.140 end-stage renal disease to someone who doesn't have it, a smoker to a non-smoker, someone with type 2

00:56:43.700 diabetes to someone who does not, those are big multipliers of risk, but they're dwarfed by

00:56:49.400 the multiplier in risk that you would go from having a very high VO2 max to a low VO2 max. Now,

00:56:55.960 of course, these associations have lots of interplay with other variables. There's some

00:57:02.360 genetic component to this, to be sure, and there's obviously a healthy user bias. So I'm not acting like

00:57:08.780 those things aren't present. But the point here is, if you can get yourself to exercise versus not,

00:57:16.640 that's a big driver of mortality reduction. And the VO2 max becomes one way that we can track the

00:57:26.120 progress you're making on that metric. Similarly with strength, similarly with muscle mass, and things

00:57:31.300 like that. Turns out, by the way, that strength matters more than muscle mass, but muscle mass is a

00:57:36.540 very good proxy for strength. You know, it's funny, I'm two days now post-op from this shoulder surgery,

00:57:41.820 and it's really interesting how much I've noticed my grip is weaker in my right hand, which is the side

00:57:49.480 I was operated on, than pre-op. So not being able to recruit the full musculature of my shoulder and

00:57:57.060 scapula on the right means I actually have slightly weaker grip in my right hand. And that's why I think

00:58:04.080 grip strength is a great proxy for longevity. It's always been known to be that way. And the question

00:58:11.940 is why? And I think there's lots of reasons. Among them, it's just a great proxy for overall body

00:58:17.220 strength and muscle mass. But I think it's also a very functional form of strength. Basically,

00:58:22.960 everything in your upper body is mediated through your hands. And if your grip is weak, everything

00:58:27.720 downstream of that is weak. When you watch someone who's got a weak grip deadlifting, it's very

00:58:33.280 difficult for them to deadlift correctly because they don't create a proper wedge. They don't

00:58:37.360 create enough tension between the bar and their torso because their grip is weak. And if they don't

00:58:42.680 create that tension, they're going to compromise their lift. And by the way, then they're more likely

00:58:47.740 to get injured. How do you train for grip strength? I mean, I assume you're not just doing those grip

00:58:54.100 curls with dumbbells, things of that nature. But how are you training specifically for grip strength?

00:58:59.840 I mean, a lot of carrying things. So I'll do a lot of supersets. I'm doing a farmer's carry in

00:59:06.560 between other workouts. One of my favorite, I won't be doing these things for quite a while,

00:59:10.620 of course, as I'm recovering, but I love doing like the ski erg. So I'll do a one minute all out ski erg

00:59:16.580 followed by a one minute farmer's carry with, I don't know, 70 pounds in each hand. So whatever that

00:59:23.180 is, probably 75% of my body weight or 80% of my body weight and just go back and forth and back and

00:59:28.120 forth between those types of things. But basically picking up heavy things is how you train for it.

00:59:33.560 You know how much I love dead hanging. So that's another great way to train grip strength.

00:59:38.580 What's your record for dead hang these days?

00:59:40.720 Well, the last long one I did was four minutes, 35 seconds.

00:59:45.500 Which is insane. And was that pre or post workout?

00:59:48.960 That was a clean day. So I was doing some katsu training, some BFR training, but not particularly

00:59:56.780 intensive on my grip. So that was a fresh start.

01:00:00.160 I'm going to ask a question, but I think we'll also have to step back and maybe let people know about

01:00:04.880 the shoulder surgery you just got because there's some gnarly videos you posted on Instagram

01:00:10.040 of it. So if anyone has a weak stomach, they might not want to look at it, but otherwise it's

01:00:16.120 pretty fascinating. So, cause my question was going to be, are you just going to start with

01:00:20.200 your shoulder in a sling, left hand, one hand dead hanging, and just really work on strengthening the

01:00:26.840 left side of your body, but also maybe let people know what you just did with your shoulder.

01:00:32.080 Yeah. So I just had shoulder surgery two days ago and it was to have my labrum repaired in the

01:00:39.160 right shoulder. Labrum is the fibrous tissue that forms a ring over the sort of flat surface of the

01:00:46.980 scapula called the glenoid fossa. And that ring of labrum is what creates the socket for the ball of

01:00:55.480 the humeral head to stay in that joint. And so because I've had so many subluxations where that 1.00

01:01:02.840 humeral head has popped out of that effective socket, that labrum has become torn. And over the

01:01:10.320 past 25 years, it's just been insult after insult after insult. And finally, I just decided I'd had

01:01:19.120 enough and it was time to have this thing fixed. What's the recovery process like? How long until

01:01:24.960 you were fully lifting like you were prior with that arm? I'm told probably about eight to nine

01:01:31.540 months. How will your exercise change? Because clearly you're not going to not exercise for eight

01:01:39.180 to nine months. It'll change in different phases. I mean, I think for the first four to six weeks,

01:01:43.440 it's going to be really quite gentle. Like all I've been doing is walking. I did ride today on the

01:01:48.580 Peloton, which I hate. You know how much I hate that piece of garbage, but it turns out the Peloton does 0.99

01:01:54.320 have one useful adaptation, which is, is easier to sit upright on a Peloton than on my regular bike. 0.97

01:02:00.460 And because I can't use my right hand to brace on the handlebar, it was just easier to sit bolt

01:02:05.880 upright on this crappy Peloton today and do my zone two ride. So I'll probably be doing that for four

01:02:11.220 to six weeks before going back to my bike where I can maybe hopefully touch the handlebars by then.

01:02:16.420 I'll be lifting, doing a ton of lower body. I'll do some left-sided upper body. And then on the right

01:02:23.000 side, as soon as I get the okay from Dr. Barron, who I'm going to see in two weeks, he's a very early

01:02:29.620 and aggressive mobilizer. That's going to be very important for me. So the reason I was dragging my

01:02:34.140 feet on this surgery was the fear of immobility. I mean, I've had a very privileged, blessed life with

01:02:40.500 very hypermobile shoulders. On my left, I was able to have hypermobility without pathology. On the right,

01:02:47.160 ultimately it turned into pathology because it was too mobile. That's what the frequent

01:02:51.420 subluxations were all about. When you have labral surgery, you're reducing mobility. And that I've

01:02:56.520 always been so afraid of that, not just because of the downstream arthritis and things like that,

01:03:00.520 but just because I can dead hang with no pain. Swimming, something I can do, which again, people

01:03:06.680 with hypermobile shoulders tend to be better at swimming. We're going to be moving early and doing

01:03:11.580 so smartly. I think that the blood flow restriction with my katsu is going to be a very important part of 0.99

01:03:17.600 that recovery and doing a lot of isometric stuff. So for example, instead of doing bicep curls with

01:03:23.300 the right, I'll do sort of isometric pressure with the blood flow restriction so that I'm not putting

01:03:29.120 the stress on the joint, but I'm still getting the muscle to work. Yeah. You're kind of documenting

01:03:34.960 everything on Instagram. And so we'll include those in the show notes, but for people who kind of want

01:03:40.360 to see more of not only the surgery itself, which you posted, but you also posted a series of videos

01:03:45.140 prior to that, which was kind of walking through what your exercise routine was. And I assume

01:03:50.460 you're going to continue. I'm just hoping we're going to get a lot of videos of you on the Peloton

01:03:54.560 because I think it's okay for you to admit that that's just a far superior bike and mode of zone

01:04:00.720 two. And maybe that's the blessing in disguise that will come of this shoulder surgery is your love

01:04:05.740 of the Peloton. Oh God, like the most ergonomically inappropriate bike ever built. Yeah. I mean,

01:04:11.400 we just need Jill to start buying you Peloton clothes. You can just replace your Viore with

01:04:16.160 the big P Peloton shirts that you can wear. I think that'd be perfect. In all seriousness,

01:04:21.240 though, the other thing that I've come to the conclusion of and just talking to you and listening

01:04:26.520 to podcasts and meetings and things of that nature is a lot of times the feedback we can get is when

01:04:32.760 you talk about some of this stuff, it's not widely available to all. When you look at some of the

01:04:39.980 drugs, it's either, it can be cost prohibitive or really tough to access them or find doctors who

01:04:47.500 will prescribe them. I mean, even what we were talking about earlier with genetic testing, the

01:04:51.980 cost prohibitive of that, the timing of that. But the thing with exercise is it's available to

01:04:57.380 everyone. It just requires a lot of hard work. But from what I've heard you saying, correct me if I'm

01:05:03.800 wrong, you still think it's one of the most potent things that people can do outside of what drugs or

01:05:10.880 supplements they take outside of other things they can do is just exercise and working on building that

01:05:17.520 muscle strength and muscle size to this day just can make such a difference in someone's not only

01:05:24.440 health span, but also ultimately their lifespan. Yeah. I mean, that's the good news and that's the bad

01:05:29.120 news. The good news is this tool called exercise, which is broad, includes a lot of things. It's not

01:05:34.740 just one thing. So by definition, it needs to be multimodal. It has an unbelievable impact on your

01:05:40.920 lifespan and health span, probably bigger than anything else. And it's available to everyone.

01:05:46.360 It has the least barrier to entry. The drawback is it's the hardest. I think it takes the most time.

01:05:53.200 That's for sure. And it's the most uncomfortable. Yeah. Anything else on exercise before we jump to

01:05:58.940 our next topic? I don't think so. On that kind of idea of supplements and drugs, anything around

01:06:07.960 molecules that you want to talk about or you've maybe changed your mind about or even gotten stronger

01:06:14.060 about anything, whether it's supplements, prescription drugs, hormones, any of those? Well, I remain

01:06:21.500 incredibly unoptimistic. I don't know if I'd call that purely pessimistic, but I remain quite uninspired

01:06:30.820 by the entire NAD stratosphere. So again, I'll be happy to be sitting here in a year or two years when

01:06:39.520 we hit 300 episodes and talk about how now I'm completely convinced that precursors to NAD are the

01:06:47.800 key to longevity. But if you'd ask me, how do I view that science today versus two years ago, I'm far

01:06:54.480 less optimistic than I was then. And I wasn't really optimistic two years ago. I mean, two years ago,

01:06:59.480 I was kind of like, meh. And now I'm three levels below meh. I just think that this is incredibly

01:07:06.540 uninspiring data so far. So I think there's evidence that you can take NAD precursors,

01:07:12.980 NR and NMN being the two most common, and increase NAD levels. I think that has been demonstrated.

01:07:19.740 I think two years ago, that was not demonstrated as clearly. I think what's not been demonstrated is

01:07:24.640 there is any phenotypic benefit from doing that outside of very pathological states. In other words,

01:07:32.660 if you take a quote unquote normal person or a normal aging person and do that, is it bringing any

01:07:40.540 benefit to them in terms of lifespan or healthspan? And I would say the answer right now is no.

01:07:46.500 It's very difficult for me to get excited about this, even though it generates a tremendous amount

01:07:51.740 of excitement on social media. Now again, happy to be proven wrong, but that will require data.

01:07:59.220 And it will not require bad data. It will require good data. I'm not going to be swayed by poorly done

01:08:06.180 studies where outcomes are not pre-selected, but are cherry picked and not corrected for in terms of

01:08:15.600 multiple looks and things like that. So some of the common problems we see with small exploratory

01:08:20.300 trials that are important to do, but should never be confused with trials that convince us of what's

01:08:26.080 going on. Yeah. And kind of a funny turn of events is this podcast is really looking at the past hundred.

01:08:32.000 I feel like we're also starting to hype up all our future podcasts accidentally because we have a

01:08:38.500 dedicated AMA we did on looking at NAD and precursors NR, NMN, as well as metformin, rapamycin,

01:08:47.620 combining all those questions. And then in addition to you answering questions on there,

01:08:52.020 we also brought back past guests, Matt Caverland. So that will be coming out in May, which will be a

01:08:58.940 very, very, very deep dive into a lot of that research and a lot of those things that you kind

01:09:05.040 of just hinted at. And going forward, I just like the idea of creating a scale of how excited you are

01:09:10.980 by how many levels up or down it is from meh.

01:09:15.140 Meh. The meh scale.

01:09:17.100 Yeah, exactly. All right. Any other things on molecules you want to touch on?

01:09:22.400 Yeah. I mean, I think there is one other thing there, which is,

01:09:24.500 and I think I talked about this in the David Nutt podcast, I believe, but it's that I do worry a

01:09:31.740 little bit about the hyper focus on psychedelics as the catch all cure all to every problem

01:09:40.980 in isolation. So maybe it speaks to the circles I travel in, but it's hard for me to go like a week

01:09:48.460 or two without talking to somebody who is raving about this shaman in Peru or this shaman here or

01:09:56.440 their psychedelic experience being life changing. But a lot of times when I get under the hood of

01:10:01.980 that a little bit, I, I realized they're describing something in isolation that I don't think is very

01:10:07.080 durable. My intuition is that those types of therapies are incredible tools to create the

01:10:16.560 vulnerability and the environment in which you can do the really deep work. And so I think there

01:10:21.520 are some people who are doing really good therapy that is guided by these types of molecules.

01:10:28.560 Specifically, I'm really talking about psilocybin and MDMA, but I think there are a lot of people

01:10:32.880 who are just taking journeys on those things, but not really pairing it with the hard work that needs

01:10:38.340 to proceed and follow it to have the lasting benefits. So I guess I would say that's just more of a

01:10:43.960 cautionary tale of, at the end of the day, I think psychotherapy is probably the most powerful tool

01:10:51.180 in different forms. Like there are lots of different types of psychotherapy, right? We're going to have

01:10:55.100 a podcast coming up on dialectical behavioral therapy, which I think is an amazing type of

01:11:00.120 therapy that's more tool oriented rather than insight oriented. So I think we want to think about

01:11:05.700 ways to use those molecules to prime us, to be ready to do that type of therapy, as opposed to just

01:11:10.680 viewing the molecule as the solution. In that sense, it's very different from a traditional drug or

01:11:16.460 molecule where the benefit I think is directly accrued from the drug. The Dave in that episode

01:11:21.900 was 182. And I can't remember if you talked about it there or if it was maybe on the podcast way back

01:11:28.400 when with Rick Doblin. But one of the things you talked about there was, you know, when these drugs,

01:11:34.560 if they become legal eventually, is the setting in which people are going to take them and the work

01:11:40.740 that's going to have to go into it before and after. Is there any update? I don't follow the space

01:11:47.180 that closely, but is there any update in terms of where we're at with those type of drugs, psilocybin,

01:11:53.860 MDMA, getting approved more widely available for trauma, PTSD, things of that nature?

01:12:00.360 So I think that the phase three data for MDMA have been marching along with a lot of promise.

01:12:09.340 So these phase three trials, which are looking at the efficacy of MDMA combined with psychotherapy

01:12:16.420 versus placebo combined with psychotherapy are demonstrating pretty impressive deltas and

01:12:22.340 improvements in reduction of PTSD symptoms. And also, I think just as importantly, there's no

01:12:27.260 toxicity. I think all of this is pointing towards a world in which we're going to see certainly MDMA

01:12:34.640 and potentially eventually psilocybin being used as adjuncts to that type of therapy. And one of the

01:12:40.860 big challenges will just be the regulatory environment in which that happens. But I see that coming to the

01:12:45.280 mainstream soon. Interesting. Before we move on to sleep, anything else on molecules you want to touch on?

01:12:52.620 No, I don't think so.

01:12:54.940 So let's move to our next category, which is sleep. So a topic that has been talked about a handful of

01:13:03.360 episodes, you know, Matt Walker has been on the podcast probably more times than anyone, maybe close

01:13:08.900 to Tom Dayspring for who's made the most appearances. But anything on sleep that you've changed your mind on

01:13:16.480 that you've been stronger upon now based on new evidence or research?

01:13:21.460 Well, I mean, I think a couple things. One, I'm probably less concerned with the light from

01:13:28.360 electronics before bed than I used to be. I think I used to view that as absolutely deadly for sleep.

01:13:36.320 I'm not sure that that's really true. It could be more the stimulation that often accompanies

01:13:41.740 blue light because blue light is often coming from electronics. It can be more the issue. So

01:13:47.480 in other words, it's might not be your phone per se that is killing you. It might be what you're

01:13:52.620 doing on your phone. So in other words, if you were looking at your phone and watching videos

01:13:56.980 of puppies and kittens and bunnies hugging each other, and then you went to bed, I'm not sure that

01:14:03.840 would disrupt your sleep. I think what's disrupting your sleep, even if you have like a blue light

01:14:09.320 blocker is if you're on Twitter. So in other words, I think between those two scenarios,

01:14:13.200 I know which one is going to be more detrimental to sleep. I think the other thing is as phenibut

01:14:20.180 has become basically impossible to acquire in the U S at least legally, you know, I've looked for

01:14:27.040 what are more appropriate sleep aids. So phenibut is a form of GABA and it was over the counter

01:14:34.020 available freely until about two years ago that easily accesses the central nervous system. And I

01:14:41.100 think anybody who's tried phenibut would tell you that this thing is an amazing sleep drug,

01:14:45.700 amazing sleep supplement. And it seemed to be one that could be used frequently without any concern,

01:14:50.960 unlike melatonin, for example, where you really have to be limited in how much melatonin you're using

01:14:55.480 and how often. So when phenibut went away, we started really paying attention to what were some other

01:15:01.460 things that we could be using. And I think what emerged as a great sleep drug for most people,

01:15:08.580 not as just a drug that you use in crisis, crisis can be anything from you're having difficulty

01:15:14.900 sleeping because there's something stressful, jet lag or something like that, but just kind of a

01:15:19.520 regular maintenance sleep drug is trazodone. Trazodone is an antidepressant, kind of an old school

01:15:24.440 antidepressant that inhibits both serotonin transporters and serotonin type two receptors.

01:15:30.960 So it's a serotonin antagonist and reuptake inhibitor. Never really took off as an antidepressant

01:15:38.780 because at the doses that one would use it as an antidepressant, it created too much drowsiness.

01:15:46.020 So in doses of 250, 300 milligrams, which produced the psychological benefits, most people just were

01:15:53.480 constantly drowsy. So it basically is a drug that went nowhere. And only recently, maybe in the

01:16:00.780 past few years, has it come to be widely accepted that this off-label use for sleep at much lower

01:16:07.580 drugs, typically 25 to 100 milligrams nightly, produces not just remarkable sleep, but more

01:16:14.000 importantly, preserves sleep architecture. Because again, the key with sleep medications is not being

01:16:19.920 unconscious. There are lots of things that can render you unconscious. Ambient renders you unconscious.

01:16:25.600 A solid right cross followed up by a left hook to the head will render you unconscious. 0.55

01:16:31.480 They're not promoting sleep architecture. In fact, if you look at Ambient, even though it might

01:16:37.120 increase total sleep time slightly, it's actually reducing slow wave or deep sleep by, depending on

01:16:45.340 the study, it can be 5 to 10 percent. You're trading good quality sleep for low quality sleep. So in the

01:16:52.740 one study that I'm looking at in particular, and we'll include this in the show notes, you see no

01:16:57.140 change in REM sleep, a reduction in non-REM deep sleep with a slight increase in total sleep, suggesting

01:17:05.120 all you did was add more light sleep. And of course, that says nothing about the other challenges that

01:17:11.100 come from drugs like Ambien, which alter your memory and things like that. Meaning anyone who's taken one of

01:17:17.340 those drugs can probably tell a scary story of how they were sending text messages or sending emails

01:17:23.940 that they don't even remember the next day. Do you want me to tell a story about you on that?

01:17:28.020 Nope. Prefer we don't. Thank you. All right. I was just double checking. Just double checking.

01:17:34.500 It's been a long time since I took one of those horrible drugs, but have the scars to remember.

01:17:39.000 We've been using trazodone pretty liberally with our patients. Doesn't work for everybody. There are some

01:17:43.240 people for whom it just doesn't work at all, meaning it doesn't produce any sedation. There are others

01:17:48.360 for whom we just can't get the right dose. Even at low doses, it produces so much sedation that the

01:17:53.520 next day they're still groggy in the morning. But for most people, and I would say that's like

01:17:58.520 north of 80%, there is a dose typically somewhere between 25 and 100 milligrams before bed that

01:18:07.200 produces remarkable sleep, both in quality, duration, and lack of interruption. And the next

01:18:13.820 morning they're fine. They don't have kind of the hangover from the medication. So again, it's a very

01:18:19.200 old school drug and it doesn't have the dependency issues that other sleep drugs often have, including

01:18:25.740 benzodiazepines, which aren't horrible for sleep architecture, but we would never prescribe them to

01:18:31.660 anybody because of the dependency issues. Why did Phenibut go away? I'm not familiar with that.

01:18:38.940 I could be wrong on this. I believe there was something in Australia where some kids took like

01:18:43.500 10 times the recommended amount and wound up in an ER. And it was just basically viewed as,

01:18:49.860 hey, this is unsafe. If kids can get their hands on this and take too much of it, which presumably you

01:18:55.540 can take too much of it, it shouldn't be legal, which of course is sort of dumb to me because the

01:19:01.140 same as two of Tylenol. If you take 10 times the maximum dose of Tylenol, you're not just going to

01:19:07.040 wind up in an ER. You're going to be dead unless they can get a liver transplant for you. If someone

01:19:11.460 took 40 grams of Tylenol in a day, which is 10 times the four grams that we would describe as the

01:19:19.180 limit, they're going to have liver failure. They're going to die. But nobody's talking about making

01:19:24.220 Tylenol illegal. To me, this was just a very bizarre decision. You know, I think it's a shame because

01:19:31.000 I think it was a really effective sleep aid. And with trozodone, is that becoming a little more

01:19:36.400 widely available? Are there a lot of doctors out there now who are understanding its potential use

01:19:43.160 for sleep because it's a prescription? So anyone listening to this would have to go through a

01:19:49.140 doctor to get a prescription. Is that something that's a little more widely knowledgeable? Or is

01:19:53.140 it if people are going to go talk to their PCP about it due to some sleep troubles, they're going to

01:19:58.940 need to go in really prepared with information? We're seeing a pretty reasonable amount of

01:20:05.620 acceptance amongst, I think, doctors that are reasonably well read. This doesn't strike me as

01:20:10.980 something that's that far outside the mainstream at this point. Got it. All right. Anything else on

01:20:18.000 sleep before we get to a few random subjects here? No, but we'll link to some of the trozodone data as

01:20:24.420 well so that people can be armed with that. Yeah, we'll put everything in the show notes. So

01:20:28.780 if people want to dive deeper into that and look at that, they can. So before we get into F1,

01:20:34.920 one thing we always like to ask is if you're reading any good books lately? I'm reading a

01:20:39.240 great book right now. I'm almost done. I like it so much that I immediately reached out to the author

01:20:43.940 to have him on the podcast. So the book is called The Comfort Crisis by Michael Easter. And I knew

01:20:49.240 Michael before this book came out. I think he'd interviewed me once for a story he was doing in

01:20:54.360 Men's Health some time ago. I'm really enjoying the book. And if people haven't read it, I recommend

01:20:59.740 it highly. I think it'll make for an awesome podcast as well. If people are interested, can you

01:21:04.480 give people just a quick little blurb about what it's about? Yeah, I mean, I think the title is pretty

01:21:09.360 self-explanatory. But basically, we are in a comfort crisis. We are way too comfortable now. And this

01:21:16.100 comfort, we live in a world where we're never hungry, we're never cold, we're never hot, we're

01:21:21.440 never bored. It's got really negative outcomes on our mental health and our physical health.

01:21:27.220 The question is, how can you exploit that information? The suggestion here is not, well,

01:21:33.040 based on that, let's go back to being hunter-gatherers and be uncomfortable 24-7 because that came with its

01:21:38.220 own problems. But the question is, what can you do in your comfortable world to get appropriate doses

01:21:43.640 of things that are uncomfortable to recoup some of the benefits?

01:21:48.680 So we're now at the point of the episode where 15% of people are probably very, very excited.

01:21:55.400 And 85% of people may drop off, which is totally fine. That's why we kept it till the end.

01:22:01.600 But we're going to talk about Formula One. So I think the best way to start this conversation

01:22:08.600 is for the people who maybe don't watch Formula One every week, haven't followed it for years.

01:22:17.540 Last year was obviously a very exciting ending that was all over the place. So I think everyone

01:22:23.300 is at least familiar with the concept that it came down to the last race. There might've been

01:22:28.560 some controversy around it. And it was all over sports side news, everything where if people

01:22:35.340 are going to start watching F1 this year and don't know all the details, it can be a little

01:22:40.640 bit of a tough sport to just throw on and get into. There's on some tracks, most tracks, maybe there's

01:22:47.040 not an overtly amount of action, not a ton of passing going on. But the more you learn about the

01:22:54.100 sport, and I can say this because there'll be times where I'm watching it and I'll be texting you,

01:22:58.840 just asking you questions about it because it's like, is this a big deal or not? What would you tell

01:23:04.020 people who are going to maybe start watching it for the first time? Because there is so much strategy.

01:23:09.260 There's so much stuff that you just don't see where you throw on basketball and you pretty much

01:23:13.660 get the point. Hockey, same thing. Baseball, this seems a little bit of a different sport. So what

01:23:19.820 would you tell people who are like, I'm going to give Formula One a shot this year. How should I think

01:23:25.020 about it? What should I watch? How do I understand it? I do think despite a lot of criticisms that have

01:23:30.180 been levied against it, the Netflix series Drive to Survive, which is now four seasons in. So we have

01:23:36.860 one season for 2018, 19, 20, and 21. I think that's a great place to start. Now, I don't think you have

01:23:44.680 to go back and watch all of them, but I think you pick a season and you watch it. And of the four

01:23:49.120 seasons so far, I don't know which one the best one was. Each one has some great episodes. Maybe season

01:23:55.560 one or three were probably the best, which is interesting because those weren't very interesting

01:23:59.520 seasons compared to season four covered the most interesting season we've had in Formula One in a

01:24:05.280 couple of decades, which was the 2021 season. But I actually don't think that the series was very

01:24:10.180 interesting. There were 10 episodes and I think four were really good and four were so-so and two

01:24:15.740 were really bad, in my opinion. But you get some understanding of what's going on. I think the

01:24:21.080 reason this sport's a bit harder to understand than basketball is there are really four variables

01:24:25.680 that determine who's going to win a race. Really five. The four things that determine how fast a

01:24:32.480 car goes plus strategy would be the five things. You can be perfect on all four of those things,

01:24:38.760 but if you have the wrong strategy, you're going to lose. So the four things are the driver,

01:24:42.840 the actual skill of the driver, the tires, because that's the only point of contact between the car

01:24:50.000 and the surface, the engine, which is what generates the power, and the chassis, which is

01:24:57.800 what allows that power to be transmitted to the tires and it confers the aerodynamics that are

01:25:05.980 necessary to go fast on curbs, which is really what differentiates F1 from any other class of motor

01:25:15.100 racing. It's not how fast those cars can go in a straight line, although they go insanely fast in

01:25:21.380 a straight line, like 320 kph, 330 kph, depending on how they tune their downforce. It's what they can

01:25:29.480 do on curbs that is literally insane. It's how much downforce they can generate. So the engine,

01:25:35.540 the chassis, the tires, the driver are the four factors that determine how fast a car is going to go.

01:25:41.400 And then the strategy for how they race is what is ultimately going to come down to, you know,

01:25:47.180 who's going to win. And now in looking at those four things, the driver obviously is different for

01:25:53.360 every team. Yeah. So there's 10 teams, two drivers per team. So you have 20 drivers in F1 on 10 teams.

01:26:01.400 And usually each team has kind of a A and a B driver. Just like on a Tour de France team,

01:26:07.480 you might have 10 cyclists. One of them is the GC contender is when the race is at the highest stakes,

01:26:12.560 like it's a Tour de France or the Giro or the Vuelta, like that's the one that everyone is in

01:26:17.240 service of. Usually one of the two drivers is the more senior driver. Now that's not always the case.

01:26:22.260 Sometimes a team is pretty equal. I think if you look at Ferrari this year with Charles Leclerc and

01:26:27.980 Carlos Sainz, I would say that either one of those guys is going to win. And I don't think the team

01:26:33.220 would employ what's called team orders, which is when the team tells one of them to get out of

01:26:38.480 the way if the other one is behind. Yeah. And that's one thing you see in the drive to survive

01:26:43.320 is those team dynamics. Just because they're on the same team, there's still competition with each

01:26:49.300 other. Yeah. On some teams, it's more than others. So on some teams, that competition between the

01:26:54.680 drivers is the most fierce because technically that guy is in a car that is most similar to yours,

01:27:00.720 though not identical. They can be tuned separately, but you're always going to be most compared to the

01:27:07.520 driver on your team. And therefore, if that person is constantly beating you, there's no ambiguity about

01:27:15.420 who's a better driver. So that's the driver. So then let's look at tires, engine, chassis. With the

01:27:21.820 rules and regulations around the cars, does everyone have access across teams to the same tires is the

01:27:28.720 question if they're hard, medium, or soft? Yeah. So Pirelli has been the tire manufacturer in F1 for

01:27:35.560 God, at least six years now. But if you look at the history of F1, sometimes you've had different

01:27:41.220 tire manufacturers in the same year. So certain teams would use Bridgestone while others would use

01:27:46.700 Michelin, Goodyear, you know, all sorts of things. But for the past, I don't remember how many years,

01:27:51.720 but it's been at least six, maybe longer. Pirelli has provided five tires throughout the year plus

01:27:58.560 the two wet weather ones. So there are seven tires that you have. And then for each race, they designate

01:28:05.880 a soft, medium, and a hard. So the five tire compounds are C1, 2, 3, 4, and 5 in increasing

01:28:12.420 hardness. And they might say C1, 2, 3 are the soft, medium, and hard for this race. Or it could be

01:28:18.540 2, 3, 4, or 4, 5, 6. And then there's an intermediate tire. And those, by the way, are always

01:28:25.160 colored red, yellow, and white. So if you look at the tire rim, you'll know it's a soft tire because

01:28:30.540 it's red. The medium for that race is the yellow and the hard is the white. Then the intermediate 0.94

01:28:36.940 is a green tire with an intermediate tread. The other ones are slick, of course. And then the blue

01:28:42.240 tire is the full weather tire. And that has a more aggressive tread. So the more tread you have,

01:28:47.140 the slower the tire is between the intermediate and the wet. And then the soft, medium, and hard

01:28:52.240 are the slick tires. And basically the trade-off here is the harder the tire, the longer it lasts

01:28:58.120 and the slower it is because it has less grip. So one of the rules of F1 is unless it's a wet or

01:29:03.860 intermediate tire, those situations are aside. But when you're using any of the dry tire compounds,

01:29:09.140 you must use at least two tires of two different compounds in a race. So what that means is even

01:29:15.060 if this were a race that were short enough that you could get away with just the hard tire,

01:29:20.500 you can't do it. You have to make at least one pit stop to switch to a different tire compound.

01:29:28.100 And obviously certain races like Bahrain last week, you'll see multiple pit stops from the teams

01:29:33.820 because the tire degradation of that circuit is so high. And that's where the strategy then it seems

01:29:39.480 like comes in. When you watch it, you see the running order of who's in first, second, third,

01:29:45.080 fourth, and then you see the tire, whether it's hard, medium or soft next to it, but it's not like

01:29:50.160 everyone is a hundred percent doing the same thing. So is that where a lot of the strategy comes in on

01:29:54.820 which tires are used at which point of the race?

01:29:57.520 Yes. And also when you switch and how many times you switch. So for example, you could run a race

01:30:04.460 on a hard and a medium and do one switch. Whereas someone else might do a soft medium and medium and

01:30:10.560 do two switches. Now, every time you switch tires, you have a guaranteed time hit of roughly 25, 26

01:30:18.000 seconds. That's about how much time is lost as you have to slow down to enter the pit, have the actual

01:30:23.520 tire change, which is taking a little longer this year than last year. This year they're based on

01:30:29.000 one race. They're probably averaging closer to three seconds. Last year was just a little over

01:30:34.220 two seconds. So it doesn't sound like much, but again, that's a relatively small price you're paying

01:30:38.400 relative to how much you have to slow down to drive into and enter the pits. So under what scenario

01:30:43.780 would you risk an extra pit stop, which costs you 25 seconds to do two stops when someone else is

01:30:51.020 doing one? Well, the answer is if you can make up half a second per lap on a 50 lap race with a

01:30:58.080 different tire strategy, then you would stay out. And by the way, there's always a risk when you do

01:31:02.200 a pit stop that something goes wrong. And that three second of actual tire changing becomes 10 seconds.

01:31:07.460 We see that all the time where it's so hard to change one of these tires. And if anything goes wrong

01:31:14.220 and a bolt gets wedged or something strips, it can be the end of the race. So your anxiety always goes

01:31:21.160 up when they enter the pit. Yeah. Well, and it's interesting too, is because it seems like one of

01:31:27.020 the best examples, maybe it's just because I haven't watched it as much of having a fresher tires. What

01:31:32.080 that does is the last race last year, because when that safety car was out for staff and pitted, got new

01:31:37.540 tires. Hamilton didn't get new tires and you saw what happened in whose car was fresher and whose

01:31:44.220 tires were faster on that last lap. Yeah. Okay. So that's tires now engine and chassis. Is that going

01:31:51.160 to be different for each team? Are there regulations around it can't exceed certain things, but there's

01:31:59.100 still flexibility in each team? How does each team do that? So as far as engines go, there are only a

01:32:06.320 handful of engine manufacturers in F1. So last year you had four. So you had Mercedes that made an

01:32:14.780 engine and they obviously made it for their car, but they also shared it with other teams. So McLaren,

01:32:19.880 Williams, Ferrari, which obviously makes for their team, but also for their sister team,

01:32:24.760 Alfa Romeo and also for Haas. And then Renault, which is the Alpine team. Renault only makes for Alpine

01:32:31.760 and then Honda for Red Bull and for their sister team, Alfa Tauri. Now Honda left the sport last

01:32:38.860 year, but Red Bull preserved the rights to the engine. So Red Bull is still using a Honda engine

01:32:44.280 as is Alfa Tauri. And then, as I said, you have Renault making for Alpine and then basically everybody

01:32:50.820 else is using a Mercedes or Ferrari engine. Now this is different from IndyCar where an IndyCar,

01:32:56.080 everybody's on the same engine. Everybody's on the same chassis. In that sense, there's something that

01:33:00.140 IndyCar has that's better than Formula One, in my opinion, which is everybody's basically in the

01:33:06.580 same car. And now the setup and the driver and the strategy play a bigger role. In F1, the engine and

01:33:15.660 the chassis, which are unique to each team, by the way, even though Mercedes makes the engine,

01:33:21.440 you can't assume that the same engine is in the Williams car. They're not getting exactly the same

01:33:26.580 engine. And the engine that the Mercedes team is using that is built by them, everything about

01:33:33.240 their car is tailored to how to use it. So Ferrari has the best Ferrari engine. Mercedes has the best

01:33:38.860 Mercedes engine. And of course, the chassis is huge. Aston Martin has a Mercedes engine, but Aston

01:33:44.980 Martin makes the chassis. And it's hard to imagine that they could ever do as good a job as Mercedes is

01:33:50.640 doing because Mercedes gets to design their chassis to pair it to a Mercedes engine. So you have very

01:33:55.960 different equipment in F1. And were there rule changes this year around the cars? Because I feel

01:34:03.120 like watching last year, there was a lot of talk. Yeah. Every few years, there's a major rule change.

01:34:08.780 It's usually every six or seven, sometimes every eight years. So this was an eight-year change. So the

01:34:13.060 last major, the way I think of it as a huge regime change in F1 was in 2013 to 2014. So prior to 2013,

01:34:21.800 Red Bull was the most dominant team of that era. So in 2011, 12, and 13, Sebastian Vettel with Red Bull

01:34:31.960 won the F1 title. And he almost won it in 2009, actually. He was so close to winning in 2009 that

01:34:40.040 for all intents and purposes, Red Bull and Vettel dominated F1 for five consecutive years. Then what

01:34:46.000 happened in 2014, the hybrid turbo era was introduced. And then Mercedes became the most

01:34:52.620 dominant team ever in the history of F1 by winning eight out of eight constructors championships and

01:34:59.140 seven out of eight drivers championships. So there's basically two championships every year.

01:35:04.000 There's the driver's championship, which is awarded to the driver with the most points. And there's the

01:35:09.220 constructors championship, which is the constructor with the most points. And those are two are not always

01:35:12.860 the same. Meaning it's not always that the team that the driver drives for is going to win. To do

01:35:19.600 that, you would have to have two relatively strong drivers, which Mercedes has historically had. Although

01:35:24.200 last year, as everybody knows, a Red Bull driver, Max Verstappen won the driver's championship, but

01:35:30.000 Mercedes was still hands down the best team and won the constructors championship because Max Verstappen

01:35:36.920 and Sergio Perez had fewer points for Red Bull than Lewis Hamilton and Valtteri Bottas had for Mercedes.

01:35:43.880 So now to your point, we have another regime change. So now the new rules that were introduced for this

01:35:49.040 year are going to readjust the pecking order. And the rules basically came down to how to make the cars

01:35:56.240 more competitive and how to create more wheel to wheel racing. So that basically reduced the downforce of

01:36:03.080 the cars, which means that when a car is following another car, it is less susceptible to the

01:36:11.160 dysregulation of airflow going over it. So Formula One cars are basically like airplanes flying upside

01:36:18.400 down. So an airplane flying right side up, the more speed going in front of the airplane, the higher it

01:36:26.780 goes up. That's what lift is. So the force of lift is equal to the surface area of the wing times the

01:36:34.780 velocity squared times the coefficient of lift. So that's why when a plane reaches its terminal height

01:36:40.240 and terminal velocity, it turns down the coefficient of lift. So it doesn't just keep going up.

01:36:45.600 Formula One race car is an upside down airplane. So the faster it goes, the harder it's being pushed

01:36:51.060 down. And to put this in perspective, last year's cars had so much aerodynamics that once they hit

01:36:59.200 about 70, maybe even 60 miles per hour, I think it was actually less than a hundred KPH. So call it 50

01:37:06.340 to 60 miles per hour. They were generating downforce that exceeded their weight. Think about what that

01:37:13.300 means. At less than a hundred kilometers per hour, they could be driving upside down. That's how much

01:37:20.300 downforce they generate. So you can imagine if you have two cars on a straightaway at 300 kilometers

01:37:26.960 per hour, they're basically stuck to the ground. But if one car is behind another car, which by

01:37:33.040 definition it needs to be to pass, its airflow is being disrupted and it's losing downforce and

01:37:39.000 therefore it's slowing down. And that creates a vicious cycle that makes it difficult to pass.

01:37:43.800 And so they wanted to make it more competitive. And it looks like they've succeeded. If you just look

01:37:48.600 at last week's race, that race was basically down to Verstappen and Leclerc until Verstappen's

01:37:53.740 engine failed. And you saw, I mean, I think five passes between the two of them, which just

01:37:59.180 historically you wouldn't have seen. So I think that's a very good change. They've also changed

01:38:03.400 the tire size. So the wheels are now bigger wheels. And I think it's super exciting because

01:38:09.200 we're basically back to square one and trying to figure out tires and engines. And they did one thing

01:38:14.120 that I think is really stupid, which is they introduced E10 fuel, which I think is just the 1.00

01:38:17.740 dumbest idea ever. It's in an effort to be sustainable, which I think is so ironic for F1 0.98

01:38:22.460 to try to be sustainable. It's like, why not an easier way to be sustainable might be scheduling

01:38:27.920 races in such a way that you don't have to fly across the world 27 times as opposed to dropping from

01:38:34.320 proper octane to E10. That has like zero bearing on the outcome compared to like one cross world flight

01:38:41.620 in the F1 schedule. So again, I think that's just a stupid example of idiotic politics that are 1.00

01:38:47.040 serving no actual advantage except making the cars drive worse. So based on those changes and based on 1.00

01:38:54.540 what we saw in week one, and again, this is recorded on March 23rd. So there hasn't been a second race.

01:39:00.700 Is it looking like this year is going to be not only more competitive in the races themselves in terms of

01:39:08.080 action passing, but also is it safe to say it's going to be more competitive in terms of the teams

01:39:15.140 that are competing because last year McLaren and Ferrari were battling a little bit for third in

01:39:21.720 the constructors, but there wasn't a lot of competition in that. I mean, last year was a pretty

01:39:27.540 good battle between first and second between Mercedes and Red Bull and then between third and fourth,

01:39:34.040 as you said, although by the end, it wasn't really much of a battle. So Mercedes pretty much

01:39:38.520 pulled ahead and then Ferrari pretty much pulled ahead of McLaren. Although I think that was less

01:39:43.820 on the basis of the cars and probably more on the basis of the performance of a couple of the

01:39:49.600 drivers. I think this year is just going to be a big reshuffling. I mean, it's so hard to say

01:39:53.920 based on preseason testing, Ferrari and Red Bull looked to be the strongest. McLaren looked to take

01:40:00.640 a step backwards. And by the way, that all looked to be true in that first race. Ferrari looked

01:40:06.620 incredibly strong going one, two. Had Verstappen and Perez not had a pump failure in their engine

01:40:12.460 in the last three laps, the order would have been Ferrari, Red Bull, Ferrari, Red Bull. Positions one,

01:40:17.480 two, three, four, and Mercedes would have been fifth, sixth. So it was clearly Ferrari, Red Bull,

01:40:23.340 then Mercedes. And McLaren was way at the back of the pack. So yeah, I think it's going to be really

01:40:28.760 interesting. McLaren has two amazing drivers in Lando Norris and Daniel Ricciardo. So you can't

01:40:34.320 blame their performance on their drivers. The other thing we saw was Haas, which is historically

01:40:39.220 for the last couple of years, the worst team in F1. They had Kevin Magnus and one of their two drivers

01:40:44.320 finish fifth. And even without the blow up of those cars, he would have been eighth, which is kind of

01:40:50.920 amazing given that they had zero points last year. And you get points anytime you're in the top 10.

01:40:54.820 The other thing I think people don't realize is the importance of qualifying. So the race on

01:41:03.760 Saturday, and then it kind of fits into another thing, which is each of these tracks is so different

01:41:10.200 that there's, from what I've picked up at least, it seems like there's some tracks that are more

01:41:14.860 competitive where if you don't qualify first, you have a chance to overtake. And there's other tracks

01:41:19.900 where if you don't qualify first, unless the first place person just does something stupid or has car 0.99

01:41:26.520 issues, they're probably going to win. Can you walk through how all that fits together and works? 0.90

01:41:32.720 The schedule for an F1 weekend is, with one exception, which I'll point out in a second,

01:41:37.840 is you always start with FP1 and FP2. Free practice one, free practice two are on Friday.

01:41:44.260 Saturday morning is FP3. That's the third practice session. And then qualifying is Saturday

01:41:48.920 afternoon. And then race is Sunday. So those are your five sessions to an F1 weekend.

01:41:54.380 The purpose of FP1, 2, and 3 is to scrub some tires. You want to get one lap on a set of tires to

01:42:01.460 basically get that sheen off them so that you have a nice set of brand new tires to get ready.

01:42:06.400 And you're also learning the track. So FP1 and FP2, it's very difficult to draw much of a conclusion for

01:42:12.900 how people are going to perform that weekend because they're really fiddling with the setup of the

01:42:18.680 car. Because as you said, every track is very different. There are some tracks where you want

01:42:23.500 very little downforce. So you want little downforce on a track that is a high speed track.

01:42:30.020 So Monza is the prototypical example. So Monza, it's called the Temple of Speed. It's the fastest

01:42:35.800 track in all of F1. And you have very little downforce there. So meaning you can't go as fast

01:42:41.580 around the corners, but you can go much faster in the straights. Conversely, you have tracks like

01:42:46.460 Suzuka in Japan, which is one of my favorite tracks, which is maximum downspeed. You have so

01:42:52.640 many high speed corners that you basically say, we're going to put all of our eggs in the downforce

01:42:58.980 basket and make sure we can go as fast as possible around these high speed corners. And we'll give up

01:43:03.740 15 miles an hour of straight line speed, if not 20 miles an hour of straight line speed. Yeah,

01:43:09.420 you probably on Suzuka are giving up 20 mile an hour straight line speed compared to Monza.

01:43:14.420 And then of course there's everything in between. So you have to fiddle with that setup as much as

01:43:19.580 possible during those practice sessions, scrub your tires. And so it's really only an FP3 Saturday

01:43:25.100 morning that you get a sense of how fast somebody can go. And then Quali works as follows. You have

01:43:30.000 what's called Q1, Q2, Q3. So Q1, everybody goes out. You basically have whatever, 12, 15 minutes to put

01:43:38.160 a lap time down. And at the end of Q1, the top 15 move on and the bottom five, their place is determined

01:43:46.580 on the grid by where they finished. And then Q2, you do the same thing again. And now it's the top 10

01:43:52.340 that go forward and places 11 to 14 are set on the grid. And then Q3 is for all the marbles. That's where

01:44:02.060 the final 10 positions are set on the grid. And so that's virtually how every race works. The grid is

01:44:08.860 determined by Quali. There are a couple of races last year where they did something called a sprint

01:44:14.200 Quali, where you do, I think they go FP1 and then Quali on Saturday. And then maybe FP2, I don't remember,

01:44:24.400 but somehow they insert an extra race in the schedule on Saturday afternoon. And that race

01:44:30.380 grid is determined by your position in qualifying, but then how you finish the race determines how

01:44:37.220 you'll finish, how you'll start the race on Sunday. So it's a short race, typically, I don't know,

01:44:43.920 16 laps or something like that. So it's about a quarter to a third, the length of the total race,

01:44:49.160 no pit stops, just go for broke. How you finish in that race determines your position. And there's

01:44:55.660 lots of pros and cons to that. I think it makes sense on some circuits. I think it probably doesn't

01:45:00.320 on some. So we'll see. I can't remember how many races are going to have it this year. I think it'll

01:45:03.680 be present again for another three or four races this year. With the qualifying, how many races do you

01:45:10.080 think where it's more important than others? Meaning what percentage of the tracks are hard to pass on

01:45:15.720 versus easier to pass on? The track that is almost impossible to pass on is Monaco. So I'd have to go

01:45:23.460 back and look at the analysis, but the analysis you'd look to do is what percentage of races are

01:45:30.380 won by pole sitters. And I think in Monaco, that's going to be the highest. And in Monaco, it's just such

01:45:35.300 a narrow track. It's very difficult to pass. Suzuka is also a very difficult track to pass on. There

01:45:40.380 were only a handful of places you can pass. Historically, Abu Dhabi was one of those tracks where you

01:45:45.460 couldn't really pass. Now they made a lot of changes last year to change the circuit, slow it down a

01:45:50.280 little bit and create more passing opportunities. But look, there's never a scenario where you're not

01:45:55.960 going to do your best in qualifying because higher grid place is always better. And this is kind of

01:46:02.280 different from the golden era of F1, which in my view was the 80s and early 90s, when you could

01:46:09.620 radically change the tuning of a car during qualifying. So if you look at the McLarens of

01:46:16.480 the mid 80s, they could boost those things to like 1400, 1600 horsepower during qualifying,

01:46:23.640 and they might race at 800 horsepower. So remember, maybe it was like 1200, 1300 versus 700 or 800. I mean,

01:46:31.140 a significant difference. And frankly, there were some drivers like Niki Lauda very famously would not

01:46:36.440 boost during qualifying. He was like, look, it's freaking dangerous. There's a good chance I'm

01:46:40.640 going to kill myself or blow up the car. He was such a good racer that he was like, I'm fine. If

01:46:45.580 I'm going to be fourth on the grid, I'm going to make it up on the grid. I'm not going to risk it.

01:46:49.960 Ayurton Senna is the best qualifying driver of all time. So if you look at the statistics of

01:46:54.360 how many pole positions relative to race starts, nobody's even close to Senna. God, he's like 63 or

01:47:04.460 something, 63 pole positions out of 161 races. I mean, that's insane. Even Hamilton and Schumacher

01:47:10.860 are nowhere near that. And Hamilton's statistically speaking, by far the greatest F1 driver of all

01:47:16.500 time. But on that one metric, nobody compares to Senna, despite the fact that his career was cut

01:47:21.460 very short. And on the strategy side, when people are watching on Sundays, what should they be watching

01:47:29.120 for on that piece? We already talked about hard, soft, medium tires. When you actually are

01:47:35.560 pitting, are there other things that people who are watching should be looking out for on that piece

01:47:42.440 to kind of understand it better? And the other thing I should say is, and I don't know how recent

01:47:47.120 this is. I haven't been watching as long as you, but it is really cool to be able to hear drivers in

01:47:52.780 real time and teams talk to drivers in real time that you don't see in any other sport. You don't hear

01:47:57.620 Bill Belichick calling plays or talking to his quarterback throughout where you do hear it in

01:48:03.160 F1. So there is that, but are there any other things that people should be looking out for

01:48:08.320 on the strategy piece on any given race to kind of understand?

01:48:12.320 It's understanding how much you push to one of the things that I really enjoy in the simulator when

01:48:17.960 I'm driving the most recent F1 cars. So the Mercedes W12, so the championship car from last year

01:48:25.620 is in iRacing, which is the simulator I use. And I love driving that car. And it's given me a totally

01:48:31.120 new appreciation for how much faster those cars can go during qualifying. And so then the question

01:48:37.280 is why? So a lot of things that determine speed are tires, softer tires are going to generally be

01:48:43.380 faster, especially new soft tires, but they might only be fast for 10 laps. And then how you discharge

01:48:49.560 the battery. So remember these are turbo hybrid cars. So they're getting probably an extra 160

01:48:55.460 or 200 horsepower out of a battery. And in qualifying, the reason they're so much faster.

01:49:01.140 So if you look at a qualifying lap, let's say you look at a qualifying lap at Interlagos, which is the

01:49:06.700 shortest circuit on the grid, but it's also one of my favorites. So the qualifying lap is probably a

01:49:11.080 minute and eight seconds. The fastest lap during the race might be a minute, 11 seconds, three seconds

01:49:18.220 difference on a lap. That might as well be a month. That's a huge difference. And the reason is the

01:49:26.140 way the car is tuned for qualifying, the way that they can maximally discharge the battery. And so

01:49:33.520 you'll hear when you're talking about the radio communications, you'll hear them say, push, push.

01:49:38.000 We sort of joke about that. If you watch enough drive to survive, you get used to hearing push,

01:49:41.280 push, box, box, because they often repeat instructions so that there's no ambiguity. Box means pit.

01:49:45.400 Push means obviously push, drive mode, push. And that's the other thing is like the drivers can't

01:49:51.580 go all out all the time. They have to protect their tires. They have to protect their batteries.

01:49:56.240 And so if a driver knows he's going to go for a big pass, he's going to have to actually back off

01:50:01.240 a little bit to recharge his battery during a lap to then be able to make a big mode push.

01:50:07.280 And then similarly with tires, like when Verstappen and Leclerc were going back and forth,

01:50:11.620 passing each other five times in two laps, they ended up taking quite a bit out of their tires.

01:50:16.960 You know, in the end, I think Leclerc had so much pace that it didn't really matter,

01:50:20.620 but that could have come back to haunt him. So those are other things you're watching for.

01:50:23.920 And a lot of times it's easier to do that in a race when you're live. Like when I'm at races live,

01:50:27.860 I'm usually timing their splits at a fixed point on the track so I can see what their time

01:50:34.820 degradation looks like per lap. Yeah. I love the thought of you just with an Excel spreadsheet and

01:50:40.180 just a stopwatch in the stands and races, just taking notes, like doing math in real time. I love

01:50:46.100 it. So to wrap up the F1 section, who is your prediction to win this year? Not only the driver,

01:50:54.420 but the team. I mean, it's going to sound like such a cop out. I can't say anything yet. I mean,

01:51:00.500 obviously if you were doing this, I mean, the smart answer is Ferrari. Ferrari looked the most

01:51:06.380 dominant during the sessions, the two testing weeks. And then they obviously went one, two in

01:51:13.960 the race. So they look pretty amazing, but look, it's a 23 race season. One of them is down and

01:51:19.560 Red Bull finished with zero points, but I mean, anything can happen going forward. And if they

01:51:24.540 can figure out what's wrong with these fuel lines, which I think is a very significant issue.

01:51:28.160 I also wonder if there's an issue with their fuel because they're using a different fuel from

01:51:32.160 everybody else. They're using Exxon as opposed to Patronus or Shell. So it might be that Exxon has

01:51:39.760 just shit the bed on this E10 mixture and there's something not working there, but three out of the 0.74

01:51:45.200 four Honda engines failed last week. So that's got to be a what's going on question. It's hard to say. 0.95

01:51:52.360 Ferrari also has two amazing drivers. Leclerc is probably the better of the two.

01:51:58.160 So I guess you would say based on that Leclerc would be kind of a early favorite, but look,

01:52:06.020 it's one race. I still think if Red Bull can figure out what they're doing, I think Max still

01:52:10.700 has a fantastic chance to win. And finally, how do you bet against Lewis Hamilton and Mercedes?

01:52:16.160 We can't forget how much they came back last year. I mean, Red Bull had almost put that championship

01:52:22.120 away with five races to go and Mercedes and Lewis Hamilton stormed back. So I would never take the

01:52:29.100 bet against Mercedes. And the difference this year is now they now have two drivers that can really

01:52:35.480 win this thing as opposed to just Hamilton. So you have George Russell, not as good as Lewis Hamilton

01:52:40.140 yet, but he's viewed largely as the heir apparent within the team. And that's why they made the somewhat

01:52:45.300 difficult decision of getting rid of Valtteri Bottas, who was an amazing wingman to Hamilton

01:52:50.500 in favor of someone who's going to be nipping at his heels more, but is also probably the future

01:52:56.300 for Mercedes. Yeah. So all that to say, it seems like at least compared to the dominance of Mercedes

01:53:02.120 in the past eight years, there's a lot more intriguing storylines and competition this first,

01:53:08.760 based on this first race compared to what we've seen in the past.

01:53:12.660 For sure. I think the competition between Hamilton and Russell is going to be intense.

01:53:17.180 I think the competition between Leclerc and Sainz could become intense, even though historically

01:53:24.020 there've been the most cordial teammates of all time that could change here. And then obviously those

01:53:29.660 three teams, Ferrari, Red Bull and Mercedes at the top is going to be intense. And anybody who's

01:53:34.860 watched Drive to Survive can appreciate the inner personal dynamics between Toto Wolff and Christian

01:53:40.940 Horner, the Mercedes and Red Bull team principals, who I think it would be an understatement to say

01:53:47.300 they can't stand each other. What was that article? Which one of the two at a charity auction bought a tour

01:53:53.180 of the other one's facility? You had Christian Horner.

01:53:56.780 That. Loved that move. Yeah. It wasn't overly expensive and just outbid everyone so he could get a

01:54:02.360 tour of the facility. I just thought that was. Which got denied by the way. He ended up not being.

01:54:06.700 Yeah. Yeah. That was pretty funny. Yeah. Just a hilarious move. All right. Anything else on F1

01:54:12.760 before we wrap this entire session? No, I think for the seven people that are still listening to this

01:54:18.680 podcast, I hope they enjoyed the little tour of F1. Yeah. No, for sure. Yeah. I think it was

01:54:25.000 just interesting. Hopefully people enjoyed kind of the more laid back conversation and just bouncing

01:54:30.440 around on topics, including this F1. So let us know feedback and we can look at doing more of these

01:54:37.240 in the future. But until then, I think we're good to go. All right, man. We'll repeat this exercise

01:54:43.780 in a hundred episodes. Yeah. Maybe we'll hit it on time this one. All right. We'll see ya. Okay.

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The Peter Attia Drive - April 11, 2022

#202 - Peter on nutrition, disease prevention, sleep, and more — looking back on the last 100 episodes

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