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

Episode Date: April 11, 2022

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter In this second edition of the “Strong Convictions, Loosely Held” episode, Peter discusses topics on which his thoughts have evolved as a result of his interviews with podcast guests and other information he’s gained since episode 100. Peter covers topics including cancer therapy and screening, as well as prevention strategies for cardiovascular disease and Alzheimer’s disease. He also describes changes in his perspectives on time-restricted feeding and protein consumption and on the therapeutic use of psychedelics, and he discusses some sleep supplements with remarkable efficacy. He ends with a special discussion on all things Formula 1 racing. We discuss: The concept of “strong convictions, loosely held” [3:10]; Update on Peter’s upcoming book [8:30]; Cancer: the promise of immunotherapy [14:15]; Cancer: how aggressive screening for gastrointestinal cancers could save lives [24:30]; Cardiovascular disease: how early and aggressive lowering of apoB could change the course of ASCVD [31:30]; Alzheimer’s disease: genes that modify risk associated with the APOE4 variant [40:15]; Time-restricted feeding: where the benefit comes from, and when this practice can be problematic [44:00]; The common problem of protein underconsumption [51:45]; The tremendous impact of exercise on lifespan and healthspan [54:45]; Peter’s shoulder surgery [1:00:15]; An uninspiring viewpoint on NAD precursors as a longevity tool [1:06:15]; Psychedelics: a powerful therapeutic tool in the right setting [1:09:30]; Sleep: updated thoughts on blue light and a remarkable drug for aiding sleep quality [1:13:15]; Book recommendation from Peter [1:20:45]; Formula 1: the 5 variables that determine the winner [1:22:00]; F1: the drivers [1:26:00]; F1: the tires [1:27:30]; F1: the engine and chassis [1:32:00]; F1: rule changes around cars [1:34:15]; F1: importance of qualifying races [1:41:15]; F1: racing strategy [1:47:30]; F1: season outlook and predictions [1:51:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Atia. This podcast, my website, and my weekly newsletter, I'll focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content and health and wellness. Full stop, and we've assembled a great team of analysts to make this happen. If you enjoy this podcast, we've created a membership program that brings you far more in-depth content if you want to take your knowledge of this space to the next level. At the end of this episode, I'll explain what those benefits are, or if you want to learn more now, head over to peteratia MD dot com forward slash subscribe.

Now without further delay, here's today's episode. Welcome to a special episode of The Drive as we celebrate our recent 200th episode. To celebrate this milestone we want to do something a little bit different, which is something we did after our first 100 episodes and that was a special episode called Strong Convictions Luselyheld. The idea of this is to basically go back and look over topics that were covered in the last 100 episodes, which is about two years, and talk about things where I've changed my mind or taken a stronger viewpoint. So in this interview, I'm once again joined by Nick Stenson.

Due to the timing of this episode, it's going to be audio only. We're trying to get this out on a very quick turnaround. So this is being recorded very shortly before it's going to be released. In this episode, we talk about a number of topics we talk about. Changes in my viewpoints around things that deal with cancer, both in terms of screening and therapeutics. We talk about my evolved thinking on atherosclerotic cardiovascular disease and around Alzheimer's disease genetics.

In the topic of nutrition, get into some changes in my views around fasting and protein consumption, talk a little bit about psychedelics under the molecules heading and exercise. We talk a lot about strength training, cardio training, and I touch a little bit on my recent surgery and the implications of that, although we're going to have a dedicated podcast on all things pertaining to that. Talk about sleep and a supplement that I used to be very bullish on that has basically vanished and then talk about a drug that I'm very excited about right now. And let's see, what else do we talk about? I think we then turn it over to a special discussion on all things Formula One. We do get a lot of questions about Formula One,

and I think that there's probably a relatively small but enthusiastic cohort of you who have a lot of questions about F1. So we end on that deliberately so that those of you who are not interested in F1 can tune out. But I think it's actually a pretty cool discussion. And I think even people who are just casually becoming interested in F1 will find this interesting. So hopefully that's more than six of you. So anyway, without further delay, please enjoy this episode celebrating 200 episodes of the drive and specifically looking back at the last hundred. All right, Peter, welcome to a special episode here. This is one you and Bob did way back for

episode 103, which is kind of this concept around strong convictions loosely held, which I'll have you explain in a second. And we did this after the first 100 episodes of the podcast. And now we just crossed episode 200. If we were a little better at planning, this would be episode 200, but episode 200. Maybe kind of... Maybe kind of... Maybe 201, technically right?

Maybe 201, but this kind of snuck up on us, so I think it's gonna be episode two, so we're only off by one. This will be a little bit of a different episode in the sense where it will kind of have an AMA feel to it where I'll be asking you some questions, but it'll be much more laid back. The prep that usually goes into a podcast

didn't really go into this one because it's more so just asking you questions around looking back at the last hundred episodes, episode 100 to 200, where has your opinion changed? Where has it maybe gotten stronger? How has it evolved? Which I think is really important for people to understand because I think sometimes they can listen to podcasts or hear people talk about things and just assume they can never change their mind or assume it doesn't evolve.

And so that's why I really like doing these. I think this will be a good one for people. And then also for the small percentage of people who are interested, we do get a lot of F1 questions. And at the end of this episode, we'll dedicate a little bit of that for all those people who really wanna dive into that. I'm cool with just doing this as a full F1 episode.

I guess for people, we're recording this on March 23rd. So we are now one race into the season and I have a lot of things I'm excited about, but I guess we'll refrain from that and we'll just make it a little F1 at the end. Yeah, a little bonus guy on there, so that will be good. But why don't we just start off by just explaining this concept of strong convictions, loosely how where it came from, your thoughts on it and why you think it's so important, especially

in the science space, the health space, things of that nature. It's a phrase that I'm sure many people have heard before and I certainly wouldn't even know where to attribute it to originally, but I can tell you where I attribute it to. I attribute it to a friend of my name, John Griffin, who used to run a very successful hedge fund. And I just remember, John, one day we were sitting around talking about his investment philosophy

and I just remember that expression coming up over and over again, which was you have to invest based on strong convictions, but they need to be loosely held. And so you have to constantly update your assumptions with new information. And I thought, wow, that's, I mean, I can see why that makes sense if you're going to be a good investor because if you invest in something based on a thesis, but you can't readjust your thesis position based on new information.

And in the words, if you're more interested in staying with a position as opposed to evolving your position, you're probably not going to be a very good investor. I realize, you know, that's kind of the same in science, medicine, and unfortunately, I think it's probably our default setting to dig our heels in on a position. So ironically, I think it's viewed as a sign of weakness or being wishy-washy when you

change your mind, certainly in politics. That's something that you get hammered for. There's no sure way to get hammered in a political debate. It seems then to have your opponent point out where you have changed your positions, someone who says, look, I used to be pro choice. 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 marriage, and now I'm in favor of it. It seems like you're posed in that position as opposed to being able to explain why you've

changed. And I understand the skepticism around politics. It could also be that people in politics are just changing their minds because they're following the political flavor of the day. But nevertheless, I think for what we do, it's important. And truthfully, last point I'll say on this, this is a big reason for why I'm not that excited about my book. So I think people listening to this probably understand I'm in the final stages of trying to finish a book. And this is a book that started in 2016. It's a book that's been basically rewritten fully once. And it sort of occurred to me a couple of months ago

that this is not a great idea. Now don't worry, I'm still gonna do it, but it's not a great idea for the following reason. Let's say I take my hands off the final manuscript in June of this year. And this thing gets published in February or March of next year. I can promise you that there are things that I'm going to have changed my mind on

that will be in print just within that nine-month period, let alone in the years that follow. So this is a form of communication where you're kind of locked into a point of view, you don't get to really update print. So there are other reasons, right? I mean, a podcast will typically reach more people than a book. We have more weekly podcast listeners than we probably have

people who are going to buy a book. So it seems to me there's very little upside for me and writing a book other than maybe it's a good excuse to just put everything in one place that's easier to digest. But nevertheless, what I love about a podcast is doing exactly what we're doing now, which is being able to consolidate all the changes in how I think about stuff. I wasn't going to bring up the book, but now that you did, I might as well ask a few questions

on it that I'm sure people will be curious about. When you talked about it previously, the draft was insanely long. This new manuscript, is it looking just as long? Is it going to be a pretty hefty size, or do you think it's going to get cut down? No, it's going to be cut down, and we're already doing an amazing job of that. We have a great editor at Penguin Random House. When we first connected, the manuscript was close to 200,000 words, she thought, well, this really ought to be 80,000 words. I said, well, it's probably not going to be that little.

But I think we're both hoping that we can converge this thing to about 120,000 words. That's still a pretty thick book. But I think that's manageable. And I think as Bill Gifford, who's my co-author and I go through this and we've been working really hard at this, we're just relentlessly pushing each other, like how can this be said in fewer words? Is this point, while interesting,

necessarily relevant to the broader point we're making? If yes, keep it, and streamline it if no, cut it. So you've probably heard me use the expression before kill your babies. This is the perfect example of killing your babies. For the folks listening, he might not cut it. So you've probably heard me use the expression before kill your babies. This is the perfect example of killing your babies. For the folks listening, he might not know what that is. That was also great advice to me, given when I was in medical school,

writing my first scientific paper. I'd put so much work into it, and I had all of these figures and all of these tables. One of the guys I was working with in the labs, look, you gotta learn to kill your babies. You're gonna do 20 experiments that are not going to make their way into the paper. And that's going to feel awkward. It's going to feel like, no, no, I need to show you as the reader of this paper, everything I've done and every experiment and every iteration.

And similarly with a book, there's a part of me that was like, I almost want the reader to be able to see how much work has gone into this. But of course, that doesn't make for a good book. Nobody needs to sit through a quarter of a million words, which is what this would easily be. So, there's lots of baby killing going on right now. I hope that that will make it better. And the only real big stress hanging over my head right now is to do the audio book or

not. I would strongly prefer not to do it, so I'm sort of in the process of exploring who could be a good reader for the book to, so I could weasel out of having to do it. Yeah, just because we're this whole podcast is on looking back at episodes, I think of the episode with Sebastian Younger, and there was some talk on there where he really talked about how he refined his writing style, and like the amount of work he would go into to only say words that really mattered. It was really impressive. So I imagine that process, especially when you're talking about such complex things as

hard. And so I think I like many people will be excited to read that when it comes out and just keep on keeping on and get that thing done. Yeah, I have mixed feelings about it. I'm still probably in the state of not liking it very much. It seems very boring to me. As I read it, I think, there's nothing new here. There's nothing exciting here. But I think every author goes through that when they've read the same thing 12 times, I just have to remind myself sometimes that for other people reading it will offer something novel.

Yeah, for sure. And for people listening, if you have strong opinions on, if an audiobook should be read by Peter, I know you put that poll on Twitter, which was really interesting, but feel free to send us a message, let us know how important you think that is. And just so people understand,

the reason I don't want to read it is there's really two fold. One, a book of this duration will take two weeks to read. For me to take two weeks off, work is a really big deal, especially to do something I don't enjoy. Let's be clear, I mean, I wouldn't enjoy this one bit. The second reason is I'm actually not a very good reader, so I think a lot of people have this assumption because I do a podcast and I don't mind public speaking. I'm a good speaker and I probably am. I'm actually a horrible reader. And I know this because I read children's books

to my kids every night and you'd think I'm in a literate moron. Even my kids catch the mistakes when I'm reading it. They're like, daddy, you miss that whole word or that sentence or whatever. So I'm not a good reader, at least not an out loud reader. So this will be an especially difficult challenge. I think there's a very good chance I won't add much value to the reading of the book, even though I have a quote unquote familiar voice.

Yeah, and you can be honest and say, you didn't accidentally miss those words. You're just trying to speed up bedtime and book reading. As any parent has done, you know, you just kind of skip a page when they're not looking and sometimes that books a lot shorter than others. That's when we discovered that Reese was Rainman, which when he was about three and a half years old and he had a book on the water cycle. This was the longest book ever. This is not a three year old kid's book.

This was like a 13 year old kid book because it took 10 to 12 minutes to read this book, which anyone reading books to kids knows. That's a long book. And I basically would start skipping paragraphs. This was only after I'd read the book four times to him in the span of, I don't know, two weeks. And he would recite the paragraphs I'd missed. And that's when we knew there was something about that kid

that was not typical to put it mildly. I actually have a video where I record him reading the entire book without reading it. And he gets it almost verbatim. Well, I mean, maybe he's your guest reader for the audiobook. We just throw a recent the booth and just let him go for a few weeks. He has to memorize it.

Someone's gonna have to read it for him four times. Bob Kaplan, we'll just send Bob out there, just let those two go at it. All right, have we wasted enough time on this? You know, he's still listening. We'll make sure in the show notes, we tell people that they can skip the first 15 minutes of this podcast.

So what we're gonna do is we're just gonna cover a few different themes and larger themes and then just talk about where your thoughts have maybe changed. So the first theme is around diseases. So this can be anything from cardiovascular disease, cancer, Alzheimer's, dementia, things of that nature. Anything that you think is really interesting there or things that you maybe change your mind on or it's gotten sharper, kind of anything you want to say there. Yeah, I'd say there are three things where my thinking today is either more clear, we're just frankly more aggressive, different than it was before. So one is around cancer,

and there are two issues specifically. One is around ASCBD, atherosclerotic cardiovascular disease, and one is around Alzheimer's disease, so I'll just take him in that order. On cancer, there are two issues. The first is around the promise of immunotherapy, and this really came out of the research that I did to prepare for one of my favorite podcasts over the past couple of years, which is the podcast with Steve Rosenberg. Folks haven't listened to that.

I can't recommend that highly enough. That was something that was very personally exciting for me. Steve was probably the most important mentor I've ever had professionally. And he's just not only one of the most remarkable scientists, but also one of the most remarkable human beings. Even though I know the field of immunotherapy quite well,

because it's not something I'm in, day in and day out, I did a lot of work to prepare for that podcast and we had a great discussion. And I think one of the things that came out of that that really blew my mind was the fact that 80% of patients have neoantigens on their cancers that are recognized by the immune system. I just want to explain why that's so significant for folks who might not appreciate it. The holy grail of cancer therapy is undoubtedly immunotherapy.

In other words, any time you can get the immune system to recognize your cancer as non-self, you're winning the game, because you get to use a cellular systemic system that could eradicate a tumor without the toxicity and failures basically associated with systemic therapies like chemotherapy. Now historically speaking very very few people meaning it's reportable in the literature it's so rare have a cancer where the immune

system can automatically recognize it at sufficient force to eradicate it. There are a couple such patients like that that Steve Rosenberg saw during his training that basically formed the impetus for his life's work. Now, there's another subset of patients, typically with cancers like melanoma and renal cell cancer, which have a high mutagenic burden, where they might not have enough immune cells to recognize and kill the cancer completely without any prompting, but if you prompt them with a cytokine like interleukin 2 at a very high dose, that is sufficient for their T-cells to go and eradicate the cancer. To put that number in context, we're talking about 10 to 20% of people with metastatic melanoma

or renal cell cancer will respond to that. Again, these are patients who would otherwise be dead in six months, and they would now go on to have durable remissions. The next step would be using something called a checkpoint inhibitor. So these are drugs that block the checkpoints on immune cells. These are basically the breaks on the immune system. And by dropping these checkpoint inhibitors on patients, so things that block either C-T-L-A-4 or PD-1 being the two most well studied of these, we have the same effect. And this isn't even broader subset of patients. But again,

it's still quite narrow in the grand scheme of things. And again, it tends to only work in patients that either have specific mutations or patients that again have a very high mutagenic burden. So people with mismatch repairs and things like that. But when you look at the fact that 80% of patients, and everything I just talked about, the spontaneous remissions, the IL-2, the checkpoint inhibitors might account for 10% of that 80. What about those other call it 70% of people? Well, I think what this finding gives us hope for is that we may in fact be able to use some combination of tumor infiltrating lymphocytes till or adaptive cell therapy where you genetically engineer T cells with that recognition. And so the reason that those patients aren't having spontaneous remissions or aren't responding to interleukin-2

or even checkpoint inhibitors is because they probably don't have enough of those T cells yet. So this now becomes just as much a bioengineering problem as it is an immunology problem, you have to be able to recognize those cells. Well, it turns out that's pretty easy to do. And now you have to be able to expand them in a manner where they still have the longevity necessary to go in and be infused into patients and basically arrest and eradicate their tumors. So all of this is a long way of saying, I really think that in 10 years, we're going to basically be using designer-based immunotherapies to eradicate most solid organ metasatic cancers. That's a bold ass statement. Let's call this beta spade. But the reason I think this is so doable is historically,

it's the impediment to this and where people I think would say today there's an impediment to this is cost. If every single person has to have their own till or adoptive cell therapy regimen created? Well, I mean, that's obviously very costly, right? That could be a couple hundred thousand dollars to generate. But the reality is, when you look at the cost of cancer therapeutics today and the failure rate, I actually think the cost of doing this is less, especially when you do it on a quality basis, so a quality adjusted life-year basis. Because today, it's not uncommon to spend $80,000 on a treatment that extends life by four months.

Well, would you rather spend $80,000 on something that's going to extend life four months, or $300,000 on something that's going to extend life indefinitely with respect to cancer? So to me, it's just going to require kind of a fundamental shift in how we do the actuarial science around durable remission therapies. So that's on the cancer front, something I'm very excited about. Let me follow up a few questions there, because I think you kind of make some big statements, and I think there was a few terminology that it would be helpful to let people know what

they are. So one is you mentioned solid organ cancers, so maybe just run through what those are. The other is you mentioned metastatic cancer, so maybe just define what that is, because I think that would be helpful. The other thing I was going to say is for those wondering, the episode with Steve Rosenberg is number 177, and it's also an amazing episode of someone who just never gave up and just was so hyper focused. If anyone hasn't listened to it, it's very technical, but the story is he tells and the stuff he was able to do

is very, very impressive. Yeah, so let me go back and answer those two points. So what does metastatic mean? Metastatic means the ability of the cancer cells to spread beyond their primary site of origin. And that's one of the two hallmarks of a cancer cell. So one of the two things that defines a cancer cell and differentiates it from a normal cell. So if you have somebody with colon cancer, what is it about the colon cancer cells that

is different from the regular colon cells? One of them is this ability to leave the colon and go someplace else. So colon cancer cells could now grow in the liver, whereas regular colon cells, if you put them in the liver, wouldn't grow. The second thing is basically the inability to respond to cell cycle signaling. A regular cell from the colon will respond to signals that tell it to stop growing. That's how it knows to stop. So if you have an injury to the colon, it will respond appropriately and grow to heal, but then it will stop growing.

Once it's told, hey, we're done, we don't need you to grow anymore. That's fine. The colon cancer cells won't do that. Those are the two hallmarks. It's not responding to growth signal, stopping, and being able to spread. To your first question, what does a solid organ tumor mean? Yeah, so it's basically anything that is not a leukemia and lymphoma, effectively.

So leukemia is in lymphomas, probably account for about 20% of cancers, and then the solid organs about 80%. That's really cancer deaths, I should say, not just cancers. So almost every time we hear about somebody dying of cancer, we're usually hearing people, someone dies of colon cancer, breast cancer, prostate cancer, brain cancer, those are what we call epithelial tumors to be more technically correct. And you mentioned the timeline 10 years. Is that timeline where this becomes a possibility? Or is that the timeline where it becomes widely available to the mass public?

Are those the same or would they be a little different? No, they'd be different. I think 10 years might be aggressive for this to be the standard of care but I think 10 years would be the time when it's going to be out of clinical trials and something that's going to be available at least to some. My guess is, unfortunately, in 10 years, I mean, again, I'm just making this up, it might not be something that is covered by insurance, which would then immediately limit to a fraction of the population that people that could get this. But it's going to have to get some traction beyond clinical trials. And there might be a period of time before this is covered. Again, I could be wrong. It could go straight from very successful clinical trials directly to something that Medicare reimburses for. But

that's what has to happen, right? I mean, unless Medicare and Medicaid reimburse for this type of treatment, it could never be widespread regardless of how successful it is. Got it. All right. Continue on with the second piece under cancer. Yeah.

So the second thing on cancer is just my complete aggression when it comes to screening for gastrointestinal cancers. Let's just kind of put big things in perspective. How many cancer deaths do we have each year? So I think for 2020, we're looking at probably 600,000 people in the US died of cancer. And how many of those were in the digestive system? 170,000 of the 600,000.

So the GI system is a really big issue, right? And that's basically everything from mouth to anus. Now, some of those things are very difficult to screen for. So pancreatic cancer, we don't really have a great way to screen for it. And that's why we use things like diffusion weighted image, MRIs, liquid biopsies, as ways to basically pursue those things.

Now we have a podcast that's coming up on liquid biopsies and all things around that. So that's going to be a very interesting podcast. We had a previous podcast that was probably on the first 100 with Raj, Uttarwala, where we talked about diffusion weighted-weighted imaging MRI for cancer screening. So if we put those things aside, the good news is that there are a lot of cancers for which we can directly take a look at the epithelial surface that is going to become cancerous. And there is no part of that that is more important than the colon. So the esophagus, the stomach,

and the colon probably represent, I don't know, 40% of those GI cancers. So again, liver and intra hepatic bile duct and pancreas are probably also about 40% and those are much harder to screen, but when you look at organ-specific sites, colon cancer is generally in the top three leading causes of death for both men and women. And what I'm about to say is going to sound incredibly bold and controversial. It seems increasingly true to me, which is nobody should ever die from colon cancer. And I would add the same for a softagel and stomach. And the reason for that is, especially in colon, the

progression from non-cancer to cancer is visible to the naked eye through the transition of non-malignant polyp to malignant polyp. So, if you did this as a thought experiment, if you did a colonoscopy on somebody every single day of their life, they would never get colon cancer. Because at some point you would see the polyp, you would remove it while it is non-cancerous and they would not get cancer. So, of course, how do you turn that thought experiment into a real life idea? Well, you have to ask the question, what is the shortest interval of time for which a

person can have a completely normal colonoscopy until they can have a cancer? There's no clear answer to this question and we've done a lot of work on it and I've spoken with a lot of gastroenterologists about it. And there are certainly some case reports that it can happen in as little as six to eight months. Of course, one has to question whether, in fact, people had perfectly normal colonoscopies six to eight months earlier, and it's possible that they did not, and that something was actually missed at the time.

But I think most people would agree that if you had a colonoscopy every one to two years, the likelihood that you could ever develop a colon cancer while maybe not zero is so remote that you could effectively take colon cancer off the list of the top 10 reasons why someone dies of cancer. So it's for that reason that I'm very aggressive when it comes to this type of screening, which also includes upper endoscopy. So you basically get for free the esophagus and stomach when you look at the entire colon rectum anus.

And what are your costs? Well your costs are obviously the dollar cost, which is not cheap. I can't tell you what the average cost of a colonoscopy, I think when I get them done, because I'm getting them done outside of regular screening. So I'm paying for them. They're certainly not cheap. I want to say maybe I'm paying 2000 for a colonoscopy. So that's a huge cost. And then there's obviously the risk of the sedation, which again is not zero. In the hands of someone who's doing this every minute of every day, it's very small. And then there's obviously the risk of the sedation, which again is not zero. In the hands of someone who's doing this every minute of every day, it's very small. And then of course, there's the risk of perforation, which again is also incredibly small, especially

in healthy individual. And even if it does happen, it's generally something that's pretty easy to manage. So again, is this something that I'm taking lightly? No, it's not. And I can't tell you yet what the ideal frequency is because at some point, for example, a colonoscopy every day would be a silly idea on all of those metrics, right? Your risk of complication is clearly going to exceed your risk of cancer, notwithstanding the cost and daily challenges of bowel preps.

So where is that number? I don't know, but it's much more frequently than what's being done today. That's what I would propose. It's not every five to ten years. So it's probably every one to three years would be my intuition. I think the other thing there and to follow up, Raj's episode is episode 61 and another good resource on this is after Chadwick Boseman passed away. We did a weekly email on it, and we'll link to it in the show notes. It's called colorectal cancer screening.

And I think the other thing that was talked about there, which you do a little different is not only the frequency, but the age in which you start your patients for their first colonoscopy. I think the standard is 50 or 45 now, but either way, you prefer much earlier. I think they are moving it down.

I mean, in our practice, we think 40 is the age at which a person should have their first colonoscopy if they have no history of colon cancer. About when I had my first one was 40 or 41, I'm 49 right now and I'm scheduled for a colonoscopy in a month and that'll probably be my fourth one. And to be clear, this requires me arguing a little bit with my primary care physician who's saying Peter, you're being a bit ridiculous.

But then I say, look, I want you to go and read whatever I've written about this. Let's hop on a call and let's discuss this in the end. He's like, okay, then you could argue, well, maybe I get my way because I'm a doctor and I can be more persuasive in my arguments. But I think these are the discussions patients need to be having with their doctors if they're in a position that they can afford to do this outside of the regular screening. And if not, I think they should push to see whatever can be done with inside the bounds of their insurance as well. I realize that we're all tainted by our biases, but the images of the people that I have seen who have had colon cancer before the age of 50, I mean, those are seared

into my brain. And that's why I think those are just such asymmetric benefits. Yeah, definitely. Okay. So I think that was the two things on cancer. I think you had a few other things in diseases that you mentioned early on. Yeah, so on ASCVD, I've also become far more aggressive on the timing and magnitude of APOB reduction. So take a step back and ask, what are the leading causes or modifiable causes

of ASCVD. The big three are pretty unambiguously smoking, hypertension, and hyperbeta lipoproteinemia, which is just a really fancy word for saying too many lipoproteins that have apo B on them. So that's LDL, ideal, VLDL, LP little A. By measuring apo B, why I'm such a fan of measuring APO B, as opposed to just measuring LP, LDL, particle number,

or LDL cholesterol number, is we have one single number that captures the total concentration of APO B. And while that's pretty well associated with non-HDL cholesterol, which is a far better surrogate than LDL cholesterol, it's still better. And that's been demonstrated, and I think we even covered that in a previous podcast, where we went over the discordance between non-HDL cholesterol and APOB. So now the question becomes, well, when should you start APOB reduction and how much should you lower it? And I'll tell you, I used to take a point of view that if a 40-year-old had an elevated APOB,

let's just put some numbers to this, right? So the 20th percentile of APOB is about 80 milligrams per deciliter. I used to say that let's say somebody was at the 50th percentile, they're 40 years old, they're calcium score is zero, and they were ambivalent about lipid lowering therapy, and let's assume that they're not insulin resistant, and you've done all the things that you can do reasonably with nutrition. I wouldn't push that hard. I've now taken a very different stand, which is I've basically taken the stand with others that I've taken with myself, which is the evidence is overwhelming that infantile levels of APOB are not

deleterious in any way, meaning an APOB of 30 to 40 milligrams per deciliter, which is the level that children would have, poses not only no risk to children as evidenced by the fact that, I mean, that doesn't require an explanation, but as evidenced by what we see in the literature on adults with levels that have been pharmacologically reduced, tells me that we need to be lower. And the amount of time it takes to see a benefit tells me we don't want to wait until there's an issue. In other words, if the reason we begin therapy is because somebody has a podative calcium score, which again, we covered this in great detail in,

is that AMA come out yet? I was just going to say that AMA will be released two weeks after this. Oh, okay, okay. Yeah, so for people listening, we have a dedicated ASCVD AMA, which goes into heavy detail for about 90 minutes on all this stuff, where if this is of interest, hang on for a few weeks and we'll be diving even deeper into it. Yeah, I got a bit lost with the recording cycle, but that's a great AMA that goes super deep on basically all of the reasons why I think my point of view now is treat early and treat aggressively. And I will now also make a very bold statement. Again, let's start with the thought experiment, right?

If the thought experiment for colon cancer was do a colonoscopy every day on a person's life, starting at the age of 30, would you eliminate colon cancer deaths? I think the answer is yes. And similarly, I would say pharmacologically lower APOB to somewhere in the 20 to 30 milligram per desoliter range for everybody in the population, while someone is in their 20s. Can you eliminate ASCVD? And I think the answer is probably yes. In other words, I think what you're basically going to do is eliminate death from atherosclerotic causes. And that would need to be started in 20s?

I think so, yeah. Very early on. Yeah, so again, how do you take that thought experiment and turn it into a practical implication because I don't think it's practical to take every 20-year-old and obliterate their APO-B, although it's clearly something we do in the subset of patients who have significant genetic abnormalities, such as the cluster of genetic abnormalities

that coalesce around a condition called familial hypercholestralemia. We certainly do medicate those patients usually as teenagers, so this is not some completely crazy idea. But I think practically what it means is basically by the time you're in your late 30s or early 40s, if you have any measure of APOB that's even north of the 20th percentile, that should be completely lowered. So in some ways, I would view an APOB ceiling of 60 as the limit. And that's probably

at about the fifth percentile. You'd sort of want everybody to be below the fifth percentile. Yeah, just because I think a lot of people listening, they might know their APOB number. And I'll also say if anyone can't wait two weeks for that AMA episode 185 with Alan Sinerman was just an amazing episode and talking about not only APOB, but just how you think about risk. Do you know the rough numbers of 20% 50% and 80% APOB just for people who maybe have their APOB metrics down, but they don't know where it relates in the percentage? Yeah, so fifth percentile from the Framingham offspring study was 62.

I just, in my mind, keep 60. 10th percentile is about 70, 20th percentile is 78. So I just think of 80, 50th percentile is about 100. It's technically 97, 80th percentile, 118. So I just kind of think of 120, 95th percentile is 140. Yeah, I mean, we're gonna see patients of all these levels. I've got a new patient whose first labs I'm reviewing very soon, I just got his labs back the other day,

his ZAPOB is, I don't know, I'm gonna say like 171. And the 95th percentile is 140. So he's, you know, in the 99.9th percentile, he almost meets diagnostic criteria for FH based on his LDL cholesterol. But you're going to see the whole spectrum here. But again, going back to this point, I just don't see a reason to have an APOB ever north of 60 milligrams per desoleter. And I think when you look at a lot of the Mendelian randomizations, plus the clinical trial data, if you have an LDL cholesterol below 30 or an APOB below 40 milligrams per deciliter for a very long period of time, I think the odds that you're going to suffer

ascvd are incredibly low. Again, the earlier you start in the lower you go, the more you can make that number approximate zero. And therefore, it then only becomes a question of what are your therapeutic choices to get there. How do you do this in a way that minimizes the side effects of that? Because for some people, to lower APOB that much, is trivial, like in me.

It's actually really easy. I take a PCSK9 inhibitor and I take a statin and I can basically eradicate it and I don't have any issues with either of those. But for some people, statins are difficult to tolerate. About 5% of the population has intractable muscle soreness and that appears to be the case regardless of which statin you use and we tend to rotate through different statins. I like to start with the Razoova statin or Pravastatin. And then if we have difficulties there, move to Patavastatin or Livolo. But if people can't tolerate any of those things, today we have so many other options.

If they're a hyper absorber, we would use a Zedemib. If they're a hyper synthesizer, but can't respond to statins, we use Mependobic Acid. So we have lots of tools up our sleeve today more than ever before, and that's why I just think we should be more and more aggressive on this now. I mean, you could say it's even a more bold statement, too, because listening to that Alan Szenterman podcast and just how many doctors, especially in the US, don't even look at ApoB. So the importance for people listening to this, too, is when they go to their doctor and

they're going to run their labs, just making sure to bring up as it possible to get an APOB ran because if they just do what a typical cholesterol panel or a typical annual exam, it might not even be looked at. Yep. Anything else on diseases that we want to cover before we go to our next subject? One last little thing I'll just say, and this will probably come up in a dedicated podcast down the line, because there's just been so much interesting stuff going on.

But I think when it comes to Alzheimer's disease, our focus now on genes outside of ApoE is pretty significant. I don't think Richard and I have ever spoken about this on a podcast, Richard Isaacson. But it's probably something we need to revisit. We're working on a paper right now that we'll get into some of this stuff,

but it turns out that there are a lot of genes that seem to modify the risk of ApoE. So anybody listening to this who's been regular listener to the podcast is undoubtedly familiar with ApoE. And it's three subtypes, type two, three and four, and of course you get two of each. You get two genes so you can have the six possible combinations there.

The fourth isoform of that is the high risk one. So if you're a two-four, it seems to more or less be a wash, maybe slight increase in risk. The three-four seems to be associated with about a 2 to 3 fold risk in Alzheimer's disease in the 4, 4, probably about an 8 to 12 fold or maybe 8 to 10 fold increase in risk. But we also know at the individual level that even though everything I just said is true at the population level, it doesn't explain what happens at the individual level because there are some individuals who walk around with 4 fours who don't seem to get Alzheimer's disease. Or if they do, they get it very late in life

and it's indistinguishable from the sort of population variant. So they're not getting this variant where they're being taken over by this disease at the age of 61 or something horrible like that. It turns out that there are a bunch of other genes that we're now starting to understand, modify the risk of E4. we're now starting to understand, modify the risk of E4. Some things make it more significant, some things make it less.

So there are certain haplotypes of the Tom 40 gene that amplify risk. There are certain mitochondrial haplotypes that amplify risk. One of the most exciting genes is the clotho modifier. I think it's KLVS is the modified snip of clotho that actually seems to erase all of the downside of APOE4. So APOE4 people who have this clotho subtype have baseline risk. So one other thing that I'm now becoming really interested in, unfortunately, the ways to measure these other genes, it's very challenging, and we have to do it by brute force today. So we don't yet have a standardized way to do this. So it takes a lot of time

and costs a lot of money to take a whole genome sequence and do the search for all of these other to take a whole genome sequence and do the search for all of these other subtypes. Takes months. A big step in the right direction here is going to be getting more data and getting those data for less than $20,000 per person. Yeah, that was going to be my follow. Question is how does someone go about getting those genes tested? Do you have a rough timeline and when that might be more widely available or even less cost prohibitive? Is that years down the road? Is that 10 years longer? It should be sooner. You know, this is a solvable problem. I think this is just about throwing enough dollars at it. And a lot of our patients have actually expressed an interest in this.

And a few of them are actually kind of working with Richard Isaacson on ways to potentially speed this up and streamline how it's done. But unfortunately, at this moment in time, whenever we do this, it is a brute force labor intensive exercise that again, we have the technical chops to be able to do if we can streamline. All right. So moving to our next category, which long time listeners will know is your absolute favorite thing to talk about. If we had a choice, you would talk about this every week and we have to usually talk you off the ledge of not doing another nutrition podcast. So anything on nutrition that you specifically want to bring up or talk about? Yeah, I think there are two things on the nutrition front that are worth talking about

where I've become more pointed in my feelings over the past, roughly two years, which I guess would be over the last 100 episodes. So the first is my view that I think most of the benefit of time restricted feeding is accrued through caloric restriction. So I've always been a little unsure of how much of the time restriction was exerting its benefit through factors that go beyond what is likely a reduced calorie intake

in someone with a smaller feeding window. So in other words, was there something magical about not eating? So if you had an experiment that was done where people are going to eat 3,000 calories a day, spread out over the course of 12 hours versus people are going to eat 3,000 calories, spread out over six hours, is there any difference

between them? And I think the answer today is no. I think the answer is, nope, when people talk about how time restricted feeding is helping them lose weight and manage insulin resistance and things like that, I think it appears that that's all due to reduced caloric intake. It's just harder to eat more during a narrow or window. And at some point, that window gets narrow enough that it's almost impossible to eat as

much as you would in the course of a day unless you're deliberately being as gluttonous as possible. And I've seen people attempt to do that for reasons I don't understand. And I think where this gets problematic is in people who can't really afford to lose too much muscle. And not completely atypical TRF scenario I see is in a patient who becomes completely obsessed with only eating in a six-hour window where you can less. And at the end of a year, they've lost five pounds. So they were kind of normal-ish weight to begin with.

They were 180 pounds to begin with, and they're 5'11s, pretty normal. And a year later, they're 175, and they're like, this is just amazing. I've lost five pounds. I feel like I can eat whatever I want. Then you do a Dexascant on them and you realize, well, you lost 10 pounds of lean tissue and you gained five pounds of fat mass. So yes, you're down five pounds,

but your body fat is actually up, I'm making this up because I'd have to do the math, but your body fat's up three percent. Your visceral fat is up by 500 grams. Nothing has moved in the right direction, except this very, very crude measurement of the number on the scale. In these individuals, I think because they're eating so much less protein, they're impairing muscle protein synthesis, so they're actually losing lean mass, even while putting on fat mass.

They're oftentimes becoming insulin resistant. I especially see this in people who are doing one meal a day, the so-called omad, especially because most people who are doing that are doing it late in the day. And so now they're having impaired glucose homeostasis overnight. We're seeing high glucose levels overnight, probably high cortisol levels and impaired glucose tolerance in the morning. So a lot of these things just aren't what we would want to see. Now there are some people for whom that still works well. So I've also seen people who lose 100 pounds and 70 of it is fat and 30 of it is lean and their net better off because they were starting at a body weight of 300 pounds and

they certainly had the amount of lean mass to improve. So their body fat maybe goes from 50% to 35%, I'm kind of making those numbers up. So they're moving in the right direction. The point here is, I think you need to ask yourself before you go on an aggressive TRF regimen, how much muscle mass can you afford to lose? And if the answer is none, which is,

it should be the answer for most people, by the way. most of us don't have the freedom to lose any lean mass. Then you got to make sure you're not restricting protein and that you're thinking about when you can refuel in relation to exercise. So Peter, when people listening are kind of trying to figure out, okay, how much muscle do they have? Can they get a baseline? And then if they are doing various diets or time restricted feeding, things of that nature, and they want to see what actually went up and down, what's the best way for them to do it? Is it a dexascan?

Is there another way outside of that where they can test this? I think dex is the only way to do it, truthfully. I mean, obviously it's not the single most accurate way to do it. There are more accurate ways to do them, but those would all be done in a research setting. Dex is relatively inexpensive. $100 in most places, maybe if you're in a place like New York, it's more. But we're talking of something in the low hundreds of dollars, not something that is thousands of dollars.

And the information it yields is also segmental, which is really valuable. So unlike the sort of buoyancy-based tests, which I think are quite inaccurate anyway, you don't get the segmental information. You don't get the information of visceral adipose tissue. So when we do a Dexascan, we're looking at lots of information. You don't get the information of visceral out of post tissue. So when we do a dexascane, we're looking at lots of information. We're looking at BMD bone mineral density, total body fat, things like that. But what I'm really interested in is what's your fat free mass index? So that's the total lean tissue in kilograms divided by height and meters squared.

The ALMI, which is the appindicular lean mass index, which is the same as the FFMI, except it's only using the lean mass of the four limbs, not including the torso. We're looking at that, and we're putting all of these things on a nomogram to see where you rank for your age and sex. And that's where I think people need to be really focused. And frankly, I care much more about those metrics than I care about your total body fat percent.

Your body fat percent is at the 40th percentile, but your ALMI, FFMI, are at the 90th percentile and your fat is at the 10th percentile, you know, it's perfectly adequate. And again, a lot of that total body fat in some ways comes down to a little bit of vanity once the biomarkers are themselves also great. Yeah, I think that was one of the most interesting things. We had an internal meeting about this

other day, which is just that surprised me how cheap a Dexascan is. And if people just search the city they're in in Dexa, I think they'd be surprised to find that out. And then same thing with VO2, and I know we'll talk about an exercise here, but some of the places that do Dexa scans can also do VO2 max tests. And so it's something that if people haven't done it, it's worth looking into and making that investment in because of what you can learn from there. The other thing, as you were talking that I thought of was, I'm gonna have to link it in the show notes,

is maybe one of the greatest commercials ever made, which is the Taco Bell Protein Commercial, and just the overall importance of protein. Before we move on, is there anything else in nutrition you wanna touch on? I think on the topic of protein, we're probably underdoing it for most people. I don't think I was paying enough attention to it.

And I think the RDAs, the recommended daily allowances are kind of out to lunch. You know, the RDA for protein is something to the tune of, I want to say it's like 0.8 grams per kilogram of body weight or something pathetic like that. You take an 80 kilogram person, so something that weighs like about a buck 75. And that person should only be eating 65 grams of protein a day or something asinine, like 0.8 to 1.

And the reality is, I think the RDA is predicated on how much protein you need to like live versus how much protein you need to like live versus how much protein you need to thrive. And so I think when you look at those data, you realize it's probably closer to two grams per kilogram or about a gram per pound of body weight and that quote-unquote toxicity of too much protein toxicity is that. Well, it's generally kidney toxicity. If you consume enough protein, you're going to overtax the kidneys because that's how we excrete the excess nitrogen. And you're looking at some of the, in the order of three to four grams per kilogram before you get into the places where you're going to start to

challenge your kidneys' abilities to take care of excess nitrogen. So this is something that we're also becoming much more attuned to in our patients. It seems to be a really big problem in middle-aged women. That's where we're probably seeing the biggest deficits are these women that show up with no muscle mass, eating no protein, doing very little strength training. I mean, to me, that is a recipe for a shorter life, but more importantly, a lower quality of life. Not to keep plugging future episodes, because I think what people may not realize is at any time of the year we have about 12 unreleased episodes.

So we kind of bank episodes episodes and just because of the nature and we do them in releasing them once a week, there's a lot that are unreleased. But a few weeks after this, so in late April, there's a follow up conversation that you and Wayne Norton had, which kind of gets into a lot of this, even in more detail, everything from the time restricted feeding to protein and even you both get in a conversation around what lane would do and how he would prescribe a workout routine, protein routine for that person, the roughly 50-year-old woman who does cardio, doesn't do a lot of strength training but needs to build in muscle. So if people want to hang on for a few more weeks to, that's coming in more detail. I think it makes sense then to kind of go a little bit on the

path we're going, which is exercise. So I don't want to say there's a lot of things that changed with your view on exercise because you've always been a big proponent of it. But from how I've even heard you talk about it, it seems you're more sold than you've ever been on the importance of exercise in someone's longevity. So do you want to maybe talk about just the theme of exercise and where you've evolved, what you're thinking is now, and why you even put more of an emphasis than before? Yeah, you're right. It seems odd that I would even be talking about this given that exercise has always been such an important part of my life personally

but I think I've now come to appreciate the magnitude of the value that is brought to a person's lifespan and health span by having higher you that is brought to a person's lifespan and health span by having higher cardio respiratory fitness and more strength. And you can't really get more strength without training. So more strength is synonymous with training, with strength training, obviously. I think I posted something on this a long time ago, or not that long ago, maybe a month

or so ago, on Instagram and Twitter, where I kind of walk through some of the data on this. We'll link to that. But the gist of it is when you look at the improvements in all cause mortality by moving up the chain of cardio-respitary fitness, so moving from being in the bottom 25th percentile to the 25th to 50th percentile, they have terminology for all of those things like low, below average, above average, high mortality drops, and it drops at levels that aren't appreciated by any other intervention. Quitting smoking, going from having end-stage renal disease to not, and it's easier to look

at these in reverse. So comparing someone with end-stage renal disease to someone who doesn't have it, a smoker to a non-smoker, someone with type 2 diabetes to someone who does not. Those are big multipliers of risk, but they're dwarfed by the multiplier in risk that you would go from having a very high VO2 max to a low VO2 max. Now of course, these associations have lots of interplay with other variables. There's some genetic component to this to be sure, and there's obviously a healthy user bias. So I'm not acting like those things aren't present,

but the point here is, if you can get yourself to exercise versus not, that's a big driver of mortality reduction. And the VO2 max becomes one way that we can track the progress you're making on that metric, similarly with strength, similarly with muscle mass, and things like that. Turns out, by the way, that strength matters more than muscle mass, but muscle mass is a very good proxy for strength. You know, it's funny. I'm two days now, post-op, from this shoulder surgery, and it's really interesting how much I've noticed my grip

is weaker in my right hand, which is the side I was operated on, then pre-op. So not being able to recruit the full musculature of my shoulder and scapula on the right means I actually have slightly weaker grip in my right hand. And that's why I think grip strength is a great proxy for longevity. It's always been known to be that way. And the question is why, and I think there's lots of reasons. Among them, it's just a great proxy for overall body strength and muscle

mass. But I think it's also a very functional form of strength. Basically, everything in your upper body is mediated through your hands. And if your grip is weak, everything downstream of that is weak. When you watch someone who's got a weak grip deadlifting, it's very difficult for them to deadlift correctly because they don't create a proper wedge. They don't create enough tension between the bar and their torso because their grip is weak. And if they don't create that tension, they're going to compromise their lift. And by the way, then, they're more likely to get injured. How do you train for grip strength?

I mean, I assume you're not just doing those grip curls with dumbbells, things of that nature, but how are you training specifically for grip strength? I mean, a lot of carrying things. So I'll do a lot of supersets. I'm doing a farmer's carry in between other workouts. One of my favorite, I won't be doing these things for quite a while, of course, as I'm recovering, but I love doing like the ski urg.

So I'll do a one minute all out ski urg, followed by a one minute farmer's carry with, I don't know, 70 pounds in each hand. So, whatever that is, probably 75% of my body weight or 80% of my body weight. And just go back and forth and back and forth between those types of things. But basically picking up heavy things

is how you train for it. You know how much I love dead hanging. So that's another great way to train grip strength. What's your record for dead hanging these days? Well, the last long one I did was four minutes, 35 seconds, which is insane. And was that pre or post workout? That was a clean day. So I was doing some katsu training, some BFR training, but not particularly intensive on

my grip. So that was a fresh start. I'm going to ask a question, but I think we'll also have to step back and maybe let people know about the shoulder surgery You just got because there's some gnarly videos you post on Instagram of it So if anyone has a weak stomach, they might not want to look at it But otherwise it's pretty fascinating. So because my question was gonna be are you just going to start with your shoulder in a sling left hand one hand dead, and just really work on

strengthening the left side of your body. But also maybe let people know what you just did with your shoulder. Yeah, so I just had shoulder surgery two days ago, and it was to have my labrum repaired in the right shoulder. The labrum is the fibrous tissue that forms a ring over the sort of flat surface of the scapula called the glenoid fossa, and that ring of labrum is what creates the socket for the ball of the humeral head to stay in that joint. And so because I've had so many sublexations where that humoral head has popped out of that effective socket that laborum has become torn.

And over the past 25 years, it's just been insult after insult after insult. And finally, I just decided I'd had enough and it was time to have this thing fixed. What's the recovery process? Like how long until you were fully lifting like you were prior with that arm? I'm told probably about eight to nine months.

How will your exercise change? Because clearly you're not going to not exercise for eight to nine months? It'll change in different phases. I mean, I think for the first four to six weeks, it's going to be really quite gentle. Like all I've been doing is walking. I mean, I think for the first four to six weeks, it's going to be really quite gentle like all I've been doing is walking. I did ride today on the Peloton, which I hate, you know, how much I hate that piece of garbage, but it turns out the Peloton does have one useful adaptation, which is easier to sit upright on the Peloton than on my regular bike, and because I can't use my right hand to brace on the handlebar, it was just easier to sit both upright on this crappy peloton today and do my zone two ride. So I'll probably

be doing that for four to six weeks before going back to my bike where I can maybe hopefully touch the handlebars by then. I'll be lifting, doing a ton of lower body, I'll do some left sided upper body and then on the right side as soon as I get the okay from Dr. Barron, who I'm gonna see in two weeks, he's a very early and aggressive mobilizer. That's gonna be very important for me. So the reason I was dragging my feet on this surgery was the fear of immobility. I mean, I've had a very privileged blessed life

with very hyper-mobile shoulders. On my left, I was able to have hyper-mobility without pathology on the right. Ultimately, it turned into pathology because it was too mobile. That's what the frequent subluxations were all about. When you have laboral surgery, you're reducing mobility, and that I've always been so afraid of that, not just because of the downstream arthritis and things like that, but just because I can dead hang with no pain, swimming, something I can do, which again, people with hypermobile shoulders tend to be better at swimming. We're going to be moving early and doing so smartly.

I think that the blood flow restriction with my katsu is going to be a very important part of that recovery and doing a lot of isometric stuff. So for example, instead of doing bicep curls with the right, I'll do sort of isometric pressure with the blood flow restriction so that I'm not putting the stress on the joint, but I'm still getting the muscle to work. Yeah, you're kind of documenting everything on Instagram, and so we'll include those in the show notes, but for people who kind of want to see more of not only the surgery itself, which you posted, but you also posted a series of videos prior to that, which was kind of walking through

what your exercise routine was, and I assume you're going to continue. I'm just hoping we're going to get a lot of videos of you on the peloton, because I think it's okay for you to admit that that's just a far superior bike and mode of zone two. And maybe that's the blessing in disguise that will come of this shoulder surgery is

your love of the peloton. Like the most ergonomically inappropriate bike ever built. Yeah, wait, I mean, we just need jail to start buying you peloton clothes. You can just replace your Viori with the big P peloton shirts that you can wear. I think that'd be perfect. In all seriousness, though, the other thing that I've come to the conclusion of and just talking to you and listening to podcasts and meetings and things of that nature is, a lot of times the feedback we can get is when you talk about some of this stuff, it's not widely available to all. When you look at some of the drugs, it can be cost prohibitive or really tough to access them or find doctors who will

prescribe them. Even what we were talking about earlier with genetic testing, the cost prohibitive of that, the timing of that. But the thing with exercise is it's available to everyone, it just requires a lot of hard work. But from what I've heard you saying, correct me if I'm wrong, you still think it's one of the most potent things that people can do outside of what drugs or supplements they take. Outside of other things they can do is just exercise and working on building that muscle strength and muscle size to this day just can make such a difference

in someone's not only health span, but also ultimately their lifespan. Yeah, I mean, that's the good news and that's the bad news. The good news is this tool called Exercise, which is broad, includes a lot of things. It's not just one thing. So by definition, it needs to be multimodal. It has an unbelievable impact on your lifespan and health span, probably bigger than anything else.

And it's available to everyone. It has the least barrier to entry. The drawback is, it's the hardest, I think. It takes the most time, that's for sure, and it's the most uncomfortable. Yeah, anything else on exercise before we jump to our next topic? I don't think so. On that kind of idea of supplements and drugs, anything around molecules that you want to talk about or you've maybe changed your mind about or even gotten stronger about anything, whether it's supplements, prescription drugs, hormones, any of those. Well, I remain incredibly unoptimistic. I don't know if I'd call that purely pessimistic, but I remain quite uninspired by the entire NAD stratosphere.

So again, I'll be happy to be sitting here in a year or two years when we hit 300 episodes and talk about how now I'm completely convinced that precursors to NAD are the key to longevity. But if you're asking me, how do I view that science today versus two years ago? I'm far less optimistic than I was then, and I wasn't really optimistic two years ago. I mean, two years ago, I was kind of like, meh, and now I'm three levels below meh. I just think that this is incredibly uninspiring data so far. So I think there's evidence that you can take NAD precursors,

and are an NMN being the two most common, and increase NAD levels. I think that has been demonstrated. I think two years ago that was not demonstrated as clearly. I think what's not been demonstrated is there is any phenotypic benefit from doing that outside of very pathological states. In other words, if you take a quote unquote normal person, a normal aging person and do that, is it bringing any benefit to them in terms of lifespan or health span? And I would say the answer right now is no. It's very difficult for me to get excited about this, even though it generates a tremendous amount of excitement on social media.

Now again, happy to be proven wrong, but that will require data, and it will not require bad data. It will require good data. I'm not going to be swayed by poorly done studies where outcomes are not pre-selected, but are cherry-picked and not corrected for in terms of multiple looks and things like that. So some of the common problems we see with small exploratory trials that are important to do, but should never be confused with trials that convince us of what's going on.

Yeah, and kind of a funny turn of events is this podcast is really looking at the past hundred. I feel like we're also starting to hype up all our future podcasts accidentally because we have a dedicated AMA we did on looking at NAD and precursors, NR, NMN, as well as metformin, repomysin, combining all those questions. And then in addition to you answering questions on there, we also brought back Pascas, Matt, K everyone. So that will be coming out in May, which will be a very, very deep dive into a lot of that research and a lot of those things that you kind of just hinted at.

And going forward, I just like the idea of creating a scale of how excited you are by how many levels up or down it is from me. The meh scale. Yeah, exactly. All right. Any other things on molecules you want to touch on? Yeah, I mean, I think there is one other thing there, which is, and I think I talked about this in the David Nut podcast, I believe, but it's that I do worry a little bit about the hyper focus on psychedelics as the catch all cure all to every problem in isolation. So maybe it speaks to the circles I travel in, but it's hard for me to go like a week or two without talking to somebody who is raving about this shaman in Peru or this shaman here or their psychedelic experience being life changing,

but a lot of times when I get under the hood of that a little bit, I realize they're describing something in isolation that I don't think is very durable. My intuition is that those types of therapies are incredible tools to create the vulnerability and the environment in which you can do the really deep work. And so I think there are some people who are doing really good therapy that is guided by these types of molecules, specifically I'm really talking about psilocybin and MDMA, but I think there are a lot of people who are just taking journeys on those things, but not really pairing it with the hard work that needs to proceed and follow it to have the lasting benefits.

So I guess I would say that's just more of a cautionary tale of at the end of the day, I think psychotherapy is probably the most powerful tool in different forms. Like there are lots of different types of psychotherapy, right? We're gonna have a podcast coming up on dialectical behavioral therapy, which I think is an amazing type of therapy that's more tool oriented rather than insight oriented.

So I think we wanna think about ways to use those molecules to prime us to be ready to do that type of therapy as opposed to just viewing the molecule as the solution. In that sense, it's very different from a traditional drug or molecule way back when with Rick Doblin, but one of the things you talked about there was, you know, when these drugs, if they become legal eventually is the setting in which people are going to take them in the work that's going to have to go into it before and after. Is there any update? I don't follow the space that closely, but is there any update in terms of where we're at with those type of drugs? So, Lassai have been MDMA have been marching along with a lot of promise. So these phase three trials, which are looking at the efficacy of MDMA combined with psychotherapy versus placebo combined with psychotherapy are demonstrating pretty impressive deltas and improvements in reduction of PTSD symptoms. And also, I think just as importantly, there's no toxicity. I think all of this is pointing towards a world in which we're going to see certainly

MDMA and potentially eventually psilocybin being used as adjuncts to that type of therapy. And one of the big challenges will just be the regulatory environment in which that happens. But I see that coming to the mainstream soon. Interesting. Before we move on to sleep, anything else on molecules you want to touch on? I don't think so. So let's move to our next category, which is sleep. So a topic that has been talked about a handful of episodes.

Matt Walker has been on the podcast probably more times than anyone, maybe close to Tom Day's spring for who's made the most appearances. But anything on sleep that you've changed your mind on that you've been stronger upon now based on new evidence or research? Well, I mean, I think a couple of things. One, I'm probably less concerned with the light from electronics before bed than I used to be. I think I used to view that as absolutely deadly for sleep. I'm not sure that that's really true.

It could be more the stimulation that often accompanies blue light because blue light is often coming from electronics that can be more the issue So in other words, it might not be your phone per se that is killing you It might be what you're doing on your phone So in other words, if you were looking at your phone and watching videos of puppies and kittens and bunnies Hugging each other and then you went to bed. I'm not sure that would Disrupt your sleep.

I think what's disrupting your sleep, even if you have like a blue light blocker, is if you're on Twitter. So in other things, between those two scenarios, I know which one is gonna be more detrimental to sleep. I think the other thing is, as fennabute has become basically impossible to acquire in the US, at least legally. I've looked for what are more appropriate sleep aids.

So, Fennabute is a form of GABA, and it was over the counter available freely until about two years ago, that easily accesses the central nervous system. And I think anybody who's tried Fennabute would tell you that this thing is an amazing sleep drug, an amazing sleep supplement. And it seemed to be one that you could be used frequently without any concern. Unlike melatonin, for example, where you really have to be limited in how much melatonin

you're using and how often. So when Phenabute went away, we started really paying attention to what were some other things that we could be using. And I think what emerged as a great sleep drug for most people, not as just a drug that you use in crisis. Crisis can be anything from you're having difficulty sleeping because there's something stressful, jet lag, or something like that, but just kind of a regular maintenance sleep drug is trasidone.

Trasidone is an antidepressant, kind of an old school antidepressant that inhibits both serotonin transporters and serotonin type 2 receptors. So it's a serotonin antagonist and reuptake inhibitor. Never really took off as an antidepressant because at the doses that one would use it as an antidepressant, it created too much drowsiness. So in doses of 253 milligrams, which produced the psychological benefits, most people just were constantly drowsy.

So it basically is a drug that went nowhere. And only recently, maybe in the past few years, has it come to be widely accepted that this off-label use for sleep at much lower drugs, typically 25 to 100 milligrams, nightly, produces not just remarkable sleep, but more importantly, preserve sleep architecture. Because again, the key with sleep medications is not being unconscious. There are lots of things that can render you unconscious. Ambient renders you unconscious. A solid right cross followed up by a left hook to the head will render you unconscious. They're not promoting sleep architecture. In fact, if you look at ambient, even though it might increase total sleep time slightly, it's actually reducing slow wave or deep sleep by depending on the study. It can be 5% to 10%.

You're trading good quality sleep for low quality sleep. So in the one study that I'm looking at in particular, and we'll include this in the show notes, you see no change in REM sleep, a reduction in non-REM deep sleep, with a slight increase in total sleep, suggesting all you did was add more light sleep. And of course, that says nothing about the other challenges

that come from drugs like ambient, which alter your memory and things like that, meaning anyone who's taken one of those drugs can probably tell a scary story of how they were sending text messages or sending emails that they don't even remember the next day. Do you want me to tell a story about you on that? Nope. Prefer we don't. Thank you.

All right. I'll just double check in. Just double check in. It's been a long time since I took one of those horrible drugs, but I have the scars to remember. We've been using Trasidone pretty liberally with our patients. It doesn't work for everybody. There are some people for whom it just doesn't work at all, meaning it doesn't produce any sedation. There are others for whom we just can't get the right dose, even at low doses it produces so much sedation that the next day they're still groggy in the morning. But for most people, and I would say that's like north of 80%, there is a dose, typically somewhere between 25 and 100 milligrams before bed, that

produces remarkable sleep, both in quality, duration, and lack of interruption, and the next morning they're fine. They don't have kind of the hangover from the medication. So again, it's a very old school drug, and it doesn't have the dependency issues that other sleep drugs often have, including benzodiazepines, which aren't horrible for sleep architecture, but we would never prescribe them to anybody

because of the dependency issues. Why did fenebuke go away? I'm not familiar with that. I could be wrong on this. I believe there was something in Australia where some kids took like 10 times the recommended amount and wound up in an ER. And it was just basically viewed as, hey, this is unsafe if kids can get their hands on this and take too much of it, which presumably you can take too much of it, it shouldn't

be legal. But of course, it's sort of dumb to me because the same as two of Tylenol. If you take 10 times the maximum dose of Tylenol, you're not just going to wind up in an ER. You're going to be dead unless they can get a liver transplant for you. If someone took 40 grams of Tylenol in a day, which is 10 times the four grams that we would describe as the limit, they're going to have liver failure. They're going to die. But nobody's talking about making Tylenol illegal. To me, this was just a very bizarre decision. I think it's a shame because I think it was a really effective sleep aid. And with Trasadone, is that becoming a little more widely available? Are there a lot of

doctors out there now who are understanding its potential use for sleep because it's a prescription. So anyone listening to this would have to go through a doctor to get a prescription. Is that something that's a little more widely knowledgeable or is it if people are going to go talk to their PCP about it due to some sleep troubles, they're going to need to go in really prepared with information.

We're seeing a pretty reasonable amount of acceptance amongst, I think, doctors that are reasonably well read. This doesn't strike me as something that's that far outside the mainstream at this point. Got it. All right. Anything else on sleep before we get to a few random subjects here? No, but we'll link to some of the Trazidone data as well so that people can be armed with that.

Yeah, we'll put everything in the show notes. So if people want to dive deeper into that and look at that, they can. So before we get into F1, one thing we always like to ask is if you're reading any good books lately. I'm reading a great book right now. I'm almost done. I like it so much that I immediately reached out to the author to have him on the podcast. So the book is called The Comfort Crisis by Michael Easter.

And I knew Michael before this book came out, I think he'd interviewed me once for a story he was doing in men's health some time ago. I'm really enjoying the book. And if people haven't read it, I recommend it highly. I think it'll make for an awesome podcast as well. If people are interested, can you give people just a quick little lard about what it's about?

Yeah, I mean, I think the title is pretty self-explanatory, but basically we are in a comfort crisis. We are way too comfortable now. And this comfort, we live in a world where we're never hungry, we're never cold, we're never hot, we're never bored. It's got really negative outcomes on our mental health and our physical health. The question is how can you exploit that information? The suggestion here is not, well, based on that, let's go back to being hunter-gatherers

and be uncomfortable 24-7 because that came with its own problems. But the question is, what can you do in your comfortable world to get appropriate doses of things that are uncomfortable to recoup some of the benefits? We're now at the point of the episode where 15% of people are probably very, very excited and 85% of people may drop off, which is totally fine. That's why we kept it till the end. But we're going to talk about Formula One. So I think the best way to start this conversation is for the people who maybe don't watch Formula

One every week haven't followed it for years. Last year was obviously a very exciting ending that was all over the place. So I think everyone is at least familiar with the concept that it came down to the last race. There might have been some controversy around it. And it was all over. Sports side news, everything where if people are going to start watching F1 this year and don't know all the details, it can be a little bit of a tough sport to just throw on and get into. There's on some tracks, most tracks, maybe there's not an overtly amount of action, not a ton of passing going on.

But the more you learn about the sport, and I can say this because there'll be times where I'm watching it and I'll be texting you, just asking you questions about it because it's like, is this a big deal or not? What would you tell people who are going to maybe start watching it for the first time? Because there is so much strategy, there's so much stuff that you just don't see where you throw on basketball and you pretty much get the point. Hockey, same thing, baseball, this seems a little bit of a different sport. So what would you tell people who are like, I'm going to give Formula One a shot this year? How should I think about it? What should I watch? How do I understand it?

I do think despite a lot of criticisms that have been levied against it, the Netflix series drive to survive, which is now four seasons in. So we have one season for 2018, 19, 20 and 21. I think that's a great place to start. Now, I don't think you have to go back and watch all of them, but I think you pick a season and you watch it. And of the four seasons so far, I don't know which one the best one was. Each one has some great episodes. Maybe season one or three were probably the best, which is interesting because those weren't very interesting seasons compared to season four covered the most interesting season we've

had in Formula One in a couple of decades, which was the 2021 season. But I actually don't think that the series was very interesting. There were 10 episodes and I think four were really good and four were so-so and two were really bad in my opinion. But you get some understanding of what's going on. I think the reason this sports a bit harder to understand than basketball is there are really four variables that Determine who's gonna win a race Really five the four things that determine how fast a car goes plus strategy would be the five things You can be perfect on all four of those things, but if you have the wrong strategy, you're gonna lose

So the four things are the driver, the actual skill of the driver, the tires, because that's the only point of contact between the car and the surface, the engine, which is what generates the power and the chassis, which is what allows that power to be transmitted to the tires, and it confers the aerodynamics that are necessary to go fast on curves, which is really what differentiates F1 from any other class of motor racing. It's not how fast those cars can go in a straight line, although they go insanely fast in a straight line, like 320 KPH, 330 kph, depending on how they tune their downforce. It's what they can do on curves that is literally insane. It's how much downforce they can generate.

So the engine, the chassis, the tires, the driver are the four factors that determine how fast the car is going to go, and then the strategy for how they race is what is ultimately going to come down to, you know, who's going to win. And now, and looking at those four things, the driver obviously is different for every team. Yeah, so there's 10 teams, two drivers per team. So you have 20 drivers in F1 on 10 teams. And usually each team has kind of a A and a B driver. Just on a tour de France team you might have 10 cyclists one of them is the gc contender is when the races at the highest

takes like it's a tour de France or the zero or the well to like that's the one that everyone is in service of. Usually one of the two drivers is the more senior driver now that's not always the case sometimes a team is equal. I think if you look at Ferrari this year with Charles LeClaire and Carlos Scyntz, I would say that either one of those guys is going to win and I don't think the team would employ what's called team orders, which is when the team tells one of them to get out of the way if the other one is behind. Yeah, and that's one thing you see in the drive to survive is those team dynamics. Just because they're on the same team, they're still competition with each other. Yeah, on some teams it's more than others.

So on some teams that competition between the drivers is the most fierce because technically that guy is in a car that is most similar to yours, though not identical. They can be tuned separately. But you're always going to be most compared to the driver though not identical. They can be tuned separately, but you're always going to be most compared to the driver on your team. And therefore, if that person is constantly beating you, there's no ambiguity about who's a better driver. So that's the driver.

So then let's look at tires, engine chassis. With the rules and regulations around the cars, does everyone have access across teams to the same tires? Is the question if they're hard, medium or soft? Yeah, so Pirelli has been the tire manufacturer in F1 for God, at least six years now. But if you look at the history of F1, sometimes you've had different tire manufacturers in the same year.

So certain teams would use bridge stone while others would use Michelin, good year, all sorts of things. But for the past, I don't remember how many years, but it's been at least six, maybe longer. Pirelli has provided five tires throughout the year, plus the two wet weather ones. So there are seven tires that you have.

And then for each race, they designate a soft medium and a hard. So the five tire compounds are C1234 and five in increasing hardness. And they might say C123 are the soft medium and hard for this race, or it could be 234 or 456. And then there's an intermediate tire. And those by the way are always colored, red, yellow, and white. So if you look at the tire rim, you'll know it's a soft tire because it's red. The medium for that race is the yellow and the hard is the white. Then the intermediate is a green tire with an intermediate tread. The other ones are slick, of course. And then the blue tire is the full weather tire, and that has a more aggressive tread. So the more tread you have, the slower the tire is between

the intermediate and the wet. And then the soft medium and harder, the slick tires, and basically the trade-off here is the harder the tire, the longer it lasts and the slower it is, because it has less grip. So one of the rules of F1 is unless it's a wet or intermediate tire, those situations are aside, but when you're using any of the dry tire compounds, you must use at least two tires of two different compounds in a race. So what that means is, even if this were a race that were short enough that you could get away with just the hard tire, you can't do it. You have to make at least one pit stop to switch to a different tire compound.

And obviously certain races like Bahrain last week, you'll see multiple pit stops from the teams because the tire degradation of that circuit is so high. And that's where the strategy that it seems like comes in. When you watch it, you see the running order of who's in first, second, third, fourth, and then you see the tire, whether it's hard, mean, or soft, next to it, but it's not like everyone is 100% doing the same thing. So is that where a lot of the strategy comes in on which tires are used at which point of the race?

Yes, and also when you switch, and how many times you switch. So for example, you could run a race on a hard and a medium and do one switch, whereas someone else might do a soft medium and medium and do two switches. Now every time you switch tires, you have a guaranteed time hit of roughly 25, 26 seconds. That's about how much time is lost as you have to slow down to enter the pit,

have the actual tire change, which is taking a little longer this year than last year. This year, they're based on one race. They're probably averaging closer to three seconds. Last year was just a little over two seconds, so it doesn't sound like much, but again, that's a relatively small price you're paying relative to how much you have to slow down to drive into and enter the pits. So under what scenario would you risk an extra pit stop, which costs you 25 seconds to do two stops when someone else is doing one? Well, the answer is if you can make up half a second per lap on a 50 lap race with a different tire strategy,

then you would stay out. And by the way, there's always a risk when you do a pit stop that something goes wrong and that three second of actual tire changing becomes 10 seconds. We see that all the time, where it's so hard to change one of these tires. And if anything goes wrong and a bolt gets wedged or something strips, it can be the end of the race. So your anxiety always goes up when they enter the pit.

Yeah. What it's interesting, too, is because it seems like one of the best examples, maybe it's just because I haven't watched as much of having to fresher tires what that does is the last race last year, because when that safety car was out for staff and pitted, got new tires, Hamilton didn't get new tires, and you saw what happened in whose car was fresher and whose tires were faster on that last lap. Yeah.

Okay, so that's tires. Now engine and chassis, is that going to be different for each team? Are there regulations around? It can exceed certain things, but there's still flexibility in each team. How does each team do that? So as far as engines go, there are only a handful of engine manufacturers in F1. So last year, you had four. So you had Mercedes that made an engine,

and they obviously made it for their car. But they also shared it with other teams. So McLaren, Williams, Ferrari, which obviously makes for their team, but also for their sister team, Alfa Romeo, and also for their sister team, alpha rameo and also for a haas. And then Renault, which is the Alpine team, Renault only makes for Alpine, and then Honda for Red Bull, and for their sister team, Alphatari.

Now, Honda left the sport last year, but Red Bull preserved the rights to the engine. So Red Bull is still using a Honda engine as is Alphatari. And then as I said, you have Renault making for Alpine. And then basically everybody else is using a Mercedes or Ferrari engine. Now, this is different from IndyCar. We're an IndyCar. Everybody's on the same engine. Everybody's on the same chassis. In that sense, there's something that IndyCar has that's better than Formula One, in my opinion, which is everybody's basically in the same car. And now the setup and the driver and the strategy play a bigger role.

In F1, the engine and the chassis, which are unique to each team, by the way, even though Mercedes makes the engine, you can't assume that the same engine is in the Williams car. They're not getting exactly the same engine. And the engine that the Mercedes team is using, that is built by them, everything about their car is tailored to how to use it. So Ferrari has the best Ferrari engine. Mercedes has the best Mercedes engine. And of course the chassis is huge. Aston Martin has a Mercedes engine, but Aston Martin makes the chassis. And it's hard to imagine that they could ever do as good a job as Mercedes is doing, because Mercedes gets the design, they're chassis to pair it to a Mercedes engine. So you have very different equipment in F1.

And were there rule changes this year around the cars? Because I feel like watching last year, there was a lot of talk. Yeah, every few years, there's a major rule change. It's usually every six or seven, sometimes every eight years. So this was an eight year change. So the last major, I think it was a huge regime change in F1 was in 2013 to 2014. So prior to 2013, Red Bull was the most dominant team of that era. So in 2011, 12 and 13 Sebastian Vettel with Red Bull won the F1 title, and he almost won it in 2009.

Actually, he was so close to winning in 2009 that front-ends and purposes, Red Bull and Vettel dominated F1 for five consecutive years. Then what happened in 2014, the hybrid turbo era was introduced, and then Mercedes became the most dominant team ever in the history of F1 by winning eight out of eight constructors championships and seven out of eight drivers championships. So there's basically two championships every year. There's the drivers championship, which is awarded to the driver with the most points. And there's the constructor's championship, which is the constructor with the most points. And those are two are not always the same. Meaning it's not always that the team that the driver drives for is going to win. To do that,

you would have to have two relatively strong drivers, which Mercedes has historically had. Although last year, as everybody knows, a Red Bull driver, Max Verstappen won the driver's championship, but Mercedes was still hands down the best team and won the Constructors' championship, because Max Verstappen and Sergio Perez had fewer points for Red Bull than Lewis Hamilton and Valtteri Bottas had for Mercedes. So now, to your point, we have another regime change. So now the new rules that were introduced for this year are going to readjust the pecking order. And the rules basically came down

to how to make the cars more competitive and how to create more wheel to wheel racing. So that basically reduced the down force of the cars, which means that when a car is following another car, it is less susceptible to the disregulation of airflow going over it. So formula one cars are basically like airplanes flying upside down. So an airplane flying right side up, the more speed going in front of the airplane, the higher it goes up. That's what lift is. So the force of lift is equal to the surface area of the wing times the velocity squared times the coefficient of lift. So that's why when a plane reaches its terminal

height and terminal velocity, it turns down the coefficient of lift, so it doesn't just keep going up. Formula 1 race car is an upside down airplane. So the faster it goes, the harder it's being pushed down. And to put this in perspective, last year's cars had so much aerodynamics that once they hit about 70, maybe even 60 miles per hour, I think it was actually less than a hundred KPH, so call it 50 to 60 miles per hour. They were generating downforce that exceeded their weight. Think about what that means. At less than a hundred kilometers per hour, they could be driving upside down. That's how much downforce they generate. So you can imagine if you have two cars on a straightaway at 300 kilometers per hour, they're basically stuck to the ground. But if one car is behind another car, which by definition it needs to be to pass, its airflow is being disrupted and it's losing down force and therefore it's slowing down. And that creates a vicious cycle that makes it difficult to pass.

And so they wanted to make it more competitive, and it looks like they've succeeded if you just look at last week's race. That race was basically down to Verstappen and LaClara until Verstappen's engine failed, and you saw, I mean, I think five passes between the two of them, which just historically you wouldn't have seen. So I think that's a very good change. They've also changed the tire size. So the wheels are now bigger wheels. And I think it's super exciting because we're basically back to square one

and trying to figure out tires and engines. And they did one thing that I think is really stupid, which is they introduced E10 fuel, which I think is just the dumbest idea ever. It's in an effort to be sustainable, which I think is so ironic for F1 to try to be sustainable. It's like, why not? An easier way to be sustainable might be scheduling races in such a way that you don't have to fly across the world 27 times as opposed to dropping from proper octane to E10. That has like zero bearing on the outcome compared to like one cross world flight in the F1 schedule.

So again, I think that's just a stupid example of idiotic politics that are serving no actual advantage except making the cars drive worse. So based on those changes, and based on what we saw in week one, and again, this is recorded on March 23rd. So there hasn't been a second race. Is it looking like this year is gonna be not only more competitive in the races

themselves in terms of action passing, but also is it safe to say it's going to be more competitive in terms of the teams that are competing? Because last year McLaren and Ferrari were battling a little bit for third in the constructors, but there wasn't a lot of competition in that. Last year was a pretty good battle between first and second, between Mercedes and Red Bull, and then between third and fourth, as you said, although by the end, it wasn't really much of a battle. Mercedes pretty much pulled ahead, and then Ferrari pretty much pulled ahead of McLaren.

Although I think that was less on the basis of the cars and probably more on the basis of the performance of a couple of the drivers, I think this year is just going to be a big reshuffling. I mean, it's so hard to say, based on preseason testing, Ferrari and Red Bull looked to be the strongest. McLaren looked to take a step backwards, and by the way, that all looked to be true in that first race. Ferrari looked incredibly strong, going one, two. Had forstappen and Perez not had a pump failure in their engine in the last three laps, the order would have been Ferrari Red Bull Ferrari Red Bull. Positions one, two, three, four, and Mercedes would have been fifth, sixth. So it was clearly Ferrari Red Bull

than Mercedes. And McLaren was way at the back of the pack. So yeah, I think it's going to be really interesting. McLaren has two amazing drivers in Landon, oris and Daniel Ricardo. So you can't blame their performance on their drivers. The other thing we saw was Haas, which is historically for the last couple of years, the worst team in F1. They had Kevin Magnus in one of their two drivers finish fifth, and even without the blowup of those cars, he would have been eighth, which is kind of amazing given that they had zero points last year. And you get points anytime you're in the top 10. The other thing I think people don't realize is the importance of qualifying.

So the race on Saturday, and then it kind of fits into another thing, which is each of these tracks is so different that there's from what I've picked up at least, it seems like there's some tracks that are more competitive, or if you don't qualify first, you have a chance to overtake. And there's other tracks where if you don't qualify first, unless the first place person just does something stupid or has car issues, they're probably gonna win. Can you walk through how all that fits together and works? The schedule for an F1 weekend is,

with one exception, which I'll point out in a second, is you always start with Fp1 and Fp2, free practice one, free practice two are on Friday. Saturday morning is Fp3, that's the third practice session, and then qualifying, free practice, 1 free practice, 2 are on Friday. Saturday morning is FP3, that's the third practice session, and then qualifying is Saturday afternoon, and then race is Sunday. So those are your five sessions to an F1 weekend. The purpose of FP1, 2 and 3 is to scrub some tires. You want to get one lap on a set of tires to basically get that sheen off them so that you

have a nice set of brand new tires to get ready. And you're also learning the track. So FP1 and FP2, it's very difficult to draw much of a conclusion for how people are going to perform that weekend because they're really fiddling with the setup of the car because, as you said, every track is very different. There are some tracks where you want very little down force. So you want little down force on a track that is a high speed track.

So Monsa is the prototypical example. So Monsa, it's called the Temple of Speed. It's the fastest track in all of F1. And you have very little down force there. So meaning you can't go as fast around the corners, but you can go much faster in the straights. Conversely, you have tracks like Suzuki in Japan, which is one of my favorite tracks,

which is maximum down speed. You have so many high speed corners that you basically say, we're gonna put all of our eggs in the downforce basket and make sure we can go as fast as possible around these high speed corners and we'll give up 15 miles an hour of straight line speed if not 20 miles an hour of straight line speed.

Yeah, you probably on Suzuki are giving up 20 mile an hour straight line speed compared to Monsa. And then of course, there's everything in between. So you have to fiddle with that setup as much as possible during those practice sessions, scrub your tires. And so it's really only an FP3 Saturday morning that you get a sense of how fast somebody can go.

And then, Kuala works as follows. You have what's called Q1, Q2, Q3. So Q1, everybody goes out. You basically have whatever, 12, 15 minutes to put a lap time down. And at the end of Q1, the top 15 move on. And the bottom five, their place is determined on the grid by where they finished.

And then Q2, you do the same thing again, and now it's the top 10 that go forward and places 11 to 14 are set on the grid. And then Q3 is for all the marbles. That's where the final 10 positions are set on the grid. And so that's virtually how every race works. The grid is determined by quality. There are a couple of races last year where they did something called a sprint quality where you do, I think they go FP1 and then quality on Saturday and then maybe FP2, I don't

remember, but somehow they insert an extra race in the schedule on Saturday afternoon, and that race grid is determined by your position in qualifying, but then how you finish the race determines how you'll start the race on Sunday. So it's a short race, typically, I don't know, 16 laps or something like that. So it's about a quarter to a third, the length of the total race. No pit stops. Just go for broke. How you finish in that race

determines your position. And there's lots of pros and cons to that. I think it makes sense on some circuits. I think it probably doesn't. So we'll see. I can't remember how many races are going to have at this year. I think it'll be present again for another three or four races this year. With the qualifying, how many races do you think where it's more important than others, meaning what percentage of the tracks are hard to pass on versus easier to pass on? The track that is almost impossible to pass on is Monaco. So I'd have to go back and look at the analysis. But the analysis you'd look to do is what percentage of races are won by poll sitters. And I think in Monaco that's going to be the highest. And in Monaco it's just such a narrow track. It's very

difficult to pass. Suzuki is also a very difficult track to pass on. There were only a handful of places you can pass. Historically Abu Dhabi was one of those tracks where you couldn't really pass. Now, they made a lot of changes last year to change the circuit, slow it down a little bit, and create more passing opportunities. But look, there's never a scenario where you're not going to do your best in qualifying because higher grid place is always better.

And this is kind of different from the golden era of F1, which in my view was the 80s and early 90s. higher grid place is always better. And this is kind of different from the golden era of F1, which in my view was the 80s and early 90s, when you could radically change the tuning of a car during qualifying. So if you look at the McLaren's of the mid 80s, they could boost those things to like 1,400, 1,600 horsepower during qualifying,

and they might race at 800 horsepower. So I remember maybe it was like 1,200, 1,300 versus 700 or 800. I mean, a significant difference. And frankly, there were some drivers like Nikki Lauda, very famously, would not boost during qualifying. He was like, look, it's friggin dangerous. There's a good chance I'm gonna kill myself

or blow up the car. He was such a good racer that he was like, I'm fine if I'm gonna be fourth on the grid. I'm gonna make it up on the grid. I'm not gonna risk it. Iron Kinsena is the best qualifying driver of all time. So if you look at the statistics of how many pole positions relative to race starts,

nobody's even close to center. God, he's like 63 or something. 63 pole positions out of 161 races. God, he's like 63 or something, 63 pole positions out of 161 races. Man, that's insane. Even Hamilton and Schumacher are nowhere near that. And Hamilton's statistically speaking by far the greatest F1 driver of all time. But on that one metric, nobody compares to center, despite the fact that his career was cut very short. And on the strategy side, when people are watching on Sundays, what should they be watching for on that piece?

We already talked about hard, soft, medium tires, when you are actually are pitting, are there other things that people who are watching should be looking out for on that piece to kind of understand it better? And the other thing should say is, and I don't know how recent this is, I haven't been watching as long as you, but it is really cool to be able to hear drivers in real time. And teams talk to drivers in real time that you don't see in any other sport.

You don't hear Bill Belichek calling plays or talking to his quarterback throughout where you do hear it in F1. So there is that, but are there any other things that people should be looking out for on the strategy piece on any given race to kind of understand? It's understanding how much you push too. One of the things that I really enjoy in the simulator when I'm driving the most recent F1 cars.

So the Mercedes W12, so the championship car from last year is in I Racing, which is the Mercedes W12, so the championship car from last year, is in I racing, which is the simulator I use, and I love driving that car. And it's given me a totally new appreciation for how much faster those cars can go during qualifying. And so then the question is why. So a lot of things that determine speed are tires, you know, softer tires are going to generally be faster, especially, you know, new soft tires, but they might only be fast for 10 laps and then how you discharge the battery. So remember, these are turbo hybrid cars. So they're getting probably an extra 160 or 200 horsepower

out of a battery. And in qualifying, the reason there's so much faster, so if you look at a qualifying lap, let's say you look at a qualifying lap at InterLogos, which is the shortest circuit on the grid, but it's also one of my favorites. So the qualifying lap is probably a minute and eight seconds. The fastest lap during the race might be a minute 11 seconds. Three seconds difference on a lap.

That must be a month. That's a huge difference. And the reason is the way the car is tuned for qualifying, the way that they can maximally discharge the battery. And so you'll hear when you're talking about the radio communications, you'll hear them say push, push. We sort of joke about that. If you watch enough drive to survive, you get used to hearing push, push, box, box,

because they often repeat instructions so that there's no ambiguity. Box means pit, push means obviously push, drive mode, push. And that's the other thing is like the drivers can't go all out all the time. They have to protect their tires. They have to protect their batteries. And so if a driver knows he's going to go for a big pass, he's going to have to actually back off a little bit to recharge his battery during a lap, to then be able to make a big mode push. And then similarly, bit tires. Like when for Stappen and LeClair, we're going back and

forth, passing each other five times in two laps, they ended up taking quite a bit out of their tires. You know, in the end, I think LeClair had so much pace that it didn't really matter, but that could have come back to Haunted. So those are other things you're watching for. And a lot of times, it's easier to do that in a race when you're live. Like when I'm at race is live, I'm usually timing their splits at a fixed point on the track. So I can see what their time degradation looks like per lap. Yeah, I love the thought of you just with the next cell spreadsheet and just a stopwatch and the stands at races just take a note. It's like doing math and real time.

Love it. So to wrap up the F1 section, who is your prediction to win this year? Not only the driver, but the team? I mean, it's going to sound like such a cop out. I can't say anything yet. I mean, obviously, if you were doing this, I mean, the smart answer is Ferrari. Ferrari looked the most dominant during the sessions, the two testing weeks, and then they

obviously went one, two in the race. So they look pretty amazing, but look, it's a 23 race season. One of them is down and Red Bull finished with zero points, but I mean, anything can happen going forward. And if they can figure out what's wrong with these fuel lines, which I think is a very significant issue, I also wonder if there's an issue with their fuel because they're using a different fuel from everybody else. They're using Exxon, supposed to Petronus or Shell.

So it might be that Exxon has just shit the bed on this E10 mixture and there's something not working there. But three out of the four Honda engines failed last week. So that's got to be what's going on question. It's hard to say Ferrari also has two amazing drivers. LeClair is probably the better of the two. So I guess you would say based on that LeClair would be kind of an early favorite. But look, it's one race. I still think if Red Bull can figure out what they're doing, I think Max still has a fantastic

chance to win. And finally, how do you bet against Lewis Hamilton and Mercedes? We can't forget how much they came back last year. I mean, Red Bull had almost put that championship away with five races to go and Mercedes and Lewis Hamilton stormed back. So I would never take the bet against Mercedes. And the difference this year is now they now have two drivers that can really win this thing as opposed to just Hamilton. So you have George Russell, not as good as Lewis Hamilton yet, but he's viewed largely

as the heir apparent within the team. And that's why they made the somewhat difficult decision of getting rid of Valtteri Bottas, who was an amazing wingman to Hamilton in favor of someone who's going to be nipping at his heels more, but is also probably the future for Mercedes. Yeah. So all that said, it seems like at least compared to the dominance of Mercedes in the past eight years, there's

a lot more intriguing storylines and competition this first based on this first race compared what we've seen the past. For sure, I think the competition between Hamilton and Russell is going to be intense. I think the competition between Lecler and science could become, even though historically there've been the most cordial teammates of all time. That could change here. And then obviously those three teams Ferrari Red Bull and Mercedes at the top is going to be intense. And anybody who's watched drive to survive can appreciate the interpersonal dynamics between total wolf and Christian Horner, the Mercedes and Red Bull team principles, who I think it would be an understatement to say they can't stand each other.

What was that article? Which one of the two had a charity auction, bought a tour of the other ones' facilities? You had Christian Horner. That loved that move. Yeah, it wasn't overly expensive and just outpin' everyone. So you could get a tour of the facility. I just thought that was...

Which got denied, by the way. He ended up not doing it. Yeah, yeah. That was pretty funny. Yeah, just a hilarious move. All right. Anything else on F1 before we wrap this entire session? No, I think for the seven people that are still listening to this podcast, I hope they enjoyed the little tour of F1. Yeah. No, for sure. Yeah, I think it was just interesting. Hopefully people enjoyed the more laid back conversation

and just bouncing around on topics, including this F1. So let us know feedback and we can look at doing more of these in the future. But until then, I think we're good to go. All right, man. We'll repeat this exercise in 100 episodes. Yeah, maybe we'll hit it on time this one. Alright, we'll see ya.

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