Tim FerrissDr. Peter Attia — Longevity Drugs, Alzheimer's Disease, and More
EVERY SPOKEN WORD
140 min read · 27,878 words- 0:00 – 3:29
Start
- TFTim Ferriss
[upbeat music] Hello, boys and girls, ladies and germs. This is Tim Ferriss, and welcome to another episode of The Tim Ferriss Show. This is a very special edition. I am in the cave of Peter Attia, Dr. Peter Attia, and we'll get back to his bio in a second. We have the incredible videographer who is trapped inside a closet to monitor levels. Everything has been fitted to perfection, and that'll all make sense shortly. Dr. Peter Attia, who can be found at Peter Attia, A-T-T-I-A, MD dot com, is a former ultra-endurance athlete, so imagine swimming races of 25 or so miles, maybe more, a compulsive self-experimenter, emphasis on compulsive, and one of the most fascinating human beings I know.
- PADr. Peter Attia
Awesome.
- TFTim Ferriss
He is one of my go-to doctors, I would say the go-to doctor for me, for anything performance or longevity-related. But here is the official bio to do him some justice. Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan, that is how long you live, while simultaneously improving healthspan, in other words, how well you live. Peter trained for five years at the Johns Hopkins Hospital in general surgery, where he was the recipient of several prestigious awards, including Resident of the Year and the author of a comprehensive review of general surgery. He also spent two years at NIH as a surgical oncology fellow at the National Cancer Institute, where his research focused on immune-based therapies for melanoma. He has since been mentored by some of the most experienced and innovative lipidologists, endocrinologists, gynecologists, sleep physiologists, and longevity scientists in the United States and Canada. Peter earned his MD from Stanford University and holds a Bachelor's of Science in Mechanical Engineering and Applied Mathematics. Peter also hosts The Drive, a weekly deep dive podcast, and I do mean deep dive, focusing on maximizing longevity and all that goes into that, including physical, cognitive, and emotional health. It features topics including fasting, ketosis, Alzheimer's disease, cancer, mental health, and much more. You can subscribe on Apple Podcasts, Spotify, Overcast, or wherever you listen to podcasts. You can find him all over the interwebs, PeterAttiaMD.com. On Twitter, @PeterAttiaMD. Instagram, same, same, Peter Attia MD. Facebook, you got it, Peter Attia MD, and then on YouTube, Peter Attia MD. Peter, welcome back to the show.
- PADr. Peter Attia
Wow. That was, that was quite an intro. [laughs]
- TFTim Ferriss
[laughs] It was an incredibly comprehensive intro.
- PADr. Peter Attia
I could have shown up a little later for this if you want to talk about it. [laughs]
- TFTim Ferriss
[laughs] So we've, we've, uh, we've had frequent flyer miles [laughs] uh, on, on podcasts, uh, including on this show, and last time we used a format that I quite enjoyed, in part because it required minimal preparation [laughs] for me, and that was going through categories, excited about, changed mind about, and stupid things or absurd things that you do. And I know that you have a number of things that you are excited about, uh, so we may spend more time in that category. Uh, so why don't you kick us off?
- PADr. Peter Attia
Well, um, so yeah. So, so the nice thing about this is I get to prepare a little bit, and I jotted down a few bullet points
- 3:29 – 15:50
Liquid Biopsy
- PADr. Peter Attia
on each. So, um, I think one of the things I'm really excited about is a very recent thing in, in that it's come to market really recently. It's been in the works for about five years, and it's something called a liquid biopsy. Um, and the reason this is interesting is that when you think about the sort of major chronic diseases, which is the diseases of atherosclerosis, so heart disease, stroke, uh, cancer, and Alzheimer's disease, we don't have a lot of great tools at detecting cancer early. Uh, so cancer screening is a somewhat controversial topic. Most people are f- probably familiar with things like mammograms, colonoscopies, and PSA testing. Um, there are two or three others that, um, rise to the level of having evidence to suggest that we do them, for example, Pap smears. Um, but when it comes to some of the really bad actors of cancer, we don't really have great screening tools. And so what a liquid biopsy does is it draws a sample of blood, and through that tries to predict whether or not you have cancer cells in your body, and tries to do so, of course, when you have very, very few of them. Because the evidence is overwhelming that all things being equal, a cancer, when caught early, at an early stage, is imminently more curable than a cancer caught at a later stage. And probably the most compelling, um, explanation for that is that the longer a cancer gets to fester in your body, the more chance it has to develop mutations, and the more mutations it generates, the more difficult it is to target later on. [lips smack] So there are a number of companies that have been doing this, but to me, the most interesting by far is a company called Grail, um, because of the method that they've gone about doing this, and the method is using something called cell-free DNA as opposed to tumor DNA.
- TFTim Ferriss
And just for those listening, Grail as in Holy Grail, the skull.
- PADr. Peter Attia
Exactly.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
Coming out big.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
Um, as a little side note, Grail was recently acquired by another company called Illumina, Illumina being the largest company that does DNA sequencing. And a very interesting note is the FTC has sued Illumina, uh, for antitrust violations in this acquisition which, if you understand the science of it, and we don't have to get into it in great detail, um, is literally the dumbest thing I've ever heard. So, uh, that the FTC has done this, in my opinion, is actually a tragedy 'cause it is actually gonna cost, um, lives. It's gonna cost tens of thousands of lives in delay if this, um, acquisition does not go through because Illumina has the power to scale this up like no other company would. Putting that aside for a moment, um, what is, what is cell-free DNA? 'Cause that's really at the heart of this technology.
- TFTim Ferriss
Say that one more time.
- PADr. Peter Attia
What is cell-free DNA?
- TFTim Ferriss
Cell-
- PADr. Peter Attia
Free DNA
- TFTim Ferriss
... like C-E-L-L, hyphen, free.
- PADr. Peter Attia
Yep. Yeah, as in DNA that's not in a cell. So most of the DNA in your body is contained within cells. Um, but when a cell breaks down, or sometimes even when cells spontaneously, like red blood cells or, or actually typically monocytes, white blood cells, make DNA and then spontaneously, like, s- release it from them, you can capture these small amounts of cell-free DNA. So if you draw somebody's blood, whether or not they have cancer or not, they're gonna have a certain amount of this cell-free DNA floating around. You have signatures on DNA called methylations. A methyl group is just a s- carbon with three hydrogens on it. It's one of the most basic building blocks of organic chemistry, and as DNA acquires these signatures, so remember DNA is made up of these four nucleotides, when they start binding these little methyl groups-
- TFTim Ferriss
That's the ACTG?
- PADr. Peter Attia
Exactly.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
ACTG. As they start acquiring these methyl groups, that tells a bit of a story, and even though there's not a lot of cell-free DNA, um, when you look at it, the best analogy, and one of my analysts actually came up with this analogy, is it's sort of like looking at, you know, meteor fragments that would land in the desert and being able to understand what type of an asteroid they came from.
- TFTim Ferriss
Hmm.
- PADr. Peter Attia
So even though the asteroid is enormous and it shed, like, big chon- chunks of meteor down to Earth, and by the time they actually hit the Earth they're just small rocks, a chemical analysis of that would give you a greater idea where it came from. So this type of test can actually de- detect up to 50 different types of cancers. There are certain ones that it's not very good at detecting, such as prostate cancer, um, which is not bad, 'cause we have other tools that are so good at detecting prostate cancer. Um, but when you do this blood test, you basically get a readout which says, "No cancer detected," or, "The following have been detected." And it does this with about a 50% sensitivity and about a 97% to 99% specificity. Now, to explain what that means in context requires a little bit of math, and it's worth going into. So sensitivity is the probability that a cancer is truly there if detected by the test, and specificity is a proba- is the probability that the cancer is not there if not detected by the test. So sensitivity speaks to true positives and specificity speaks to true negatives. Now at first, 50% sensitivity doesn't sound that good, but you have to remember it depends on what we call the pre-test probability is. So pre-test probability says, what is the probability that you have cancer before I test you? And that's a function of many things. It's a function of the prevalence of that cancer, it's a prev-- it's a function of your age, it's a function of other behaviors. So for example, two people being otherwise identical except one being a smoker and one not being a smoker are gonna have very different pre-test probabilities. But when you start to think about [clears throat] for example you, what's your pre-test probability of having pancreatic cancer? It's quite low, fortunately, even though pancreatic cancer is one of the most lethal cancers out there. So in a low probability environment, a modest sensitivity of 50% and a very high, uh, specificity produces incredible what we call positive and negative predictive value. So what do those things mean? So positive predictive value, as it sounds, means what's the probability that if you get a positive test you truly have cancer, and negative predictive value is, of course, if you have a negative test, what's the probability it's negative? These numbers end up being well north of 90%. In fact, the negative predictive value is about 99.7%. The positive predictive value is in the ballpark of about 97%. So these are really exciting tests, especially when you pair them with some of the other things that we do in our practice, such as relying on a very special type of MRI technology that uses something called diffusion weighted imaging that adds sort of a functional dimension to MRI.
- TFTim Ferriss
Quick note there. People can, if they really want to deep dive [chuckles] into that subject matter, you have a guest on your podcast, and I've, I've listened to this episode. It get, does get quite technical, but-
- PADr. Peter Attia
That's right
- TFTim Ferriss
... what is the guest's name for people who wanna, wanna search?
- PADr. Peter Attia
Raj, R-A-J, uh, and how do you spell his last name? A-T-T-R-A-A-W-A-L. Of course, I can't spell in my head, but if you just search Raj MRI, it'll, it'll pop up.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
Um, and yes, that's, that's an episode we usually make our patients listen to before they go and get one of those MRIs so they understand it.
- TFTim Ferriss
Follow-up to that, un- unrelated but, uh, related to GRAIL, what is it that happened or what technology was developed that suddenly made this possible where it was not possible before? Or what realization? Why did this suddenly come to fruition or-
- PADr. Peter Attia
Yeah
- TFTim Ferriss
... or, or only now become available?
- PADr. Peter Attia
Yeah, I, I think the major insight, and I will be doing a podcast on this, but I need to wait until this FTC issue [chuckles] is resolved a little bit, because the person that I really wanna interview for the podcast, who is one of the people that had the biggest hand in developing this, um, is actually now the chief scientific officer at Illumina. And so for him to be able to speak about it, obviously it would need to make sense that Illumina actually owns the technology again. Uh, I would say, and this might change as I get deeper into understanding their journey, I think it was the realization that tumor f- that, that tumor DNA was not the place to go. So at the outset of this process, people didn't know what to look for. Would you look for RNA of tumors? 'Cause RNA is the, you know, it's the template that's telling you to make the protein, and that didn't really pan out because RNA is so unstable by itself. So then pivoting to DNA, the logical choice was, well, let's look for the tumor DNA. You know, if you have pancreatic cancer and we can find the DNA of a pancreatic cancer cell, that would be a good place to start. But you're, you have to be looking for cell-free DNA by definition when you're doing a liquid biopsy, 'cause you're not gonna sample the organ. And it turns out that tumor DNA represents about .1% of cell-free DNA. So I think the big aha for GRAIL was realizing, no, let's look at cell-free DNA, which is much more abundant, but instead look at the methylation patterns, and then specifically figure out what those methylation patterns were. So that was the real puzzle.
- TFTim Ferriss
Yeah, the, the forensic science.
- 15:50 – 19:22
Four pillars of exercise
- PADr. Peter Attia
time.
- TFTim Ferriss
So you mentioned in terms of prevention, metabolically healthy. Is there anything you're excited about or would like to underscore that relates to developing metabolic health or improving metabolic health?
- PADr. Peter Attia
Always. Um, I'd say, you know, exercise is so important, right? It, it can't be overstated. It's potentially one of the most potent drugs we have.
- TFTim Ferriss
But all exercise is not created equal, I would imagine.
- PADr. Peter Attia
Correct. And-
- TFTim Ferriss
For this purpose.
- PADr. Peter Attia
Ab- absolutely. Um, and so I, I think of exercise as having four pillars, and, um, you have to be strong on each of those. So if you're strong in three but not in one, it's sort of like a table that has three legs and not one. It's still a reasonable table, but it's not as strong as a table with four legs. And a table with two legs is pretty pathetic, and obviously a table with one leg is not a table.
- TFTim Ferriss
[chuckles]
- PADr. Peter Attia
So the four pillars are stability, strength, aerobic efficiency, and anaerobic performance. And I think that most people understand loosely what three of those are.
- TFTim Ferriss
Could you say those all one more time?
- PADr. Peter Attia
Sure. Stability.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
That's the one that most people don't understand. We can talk about that in a minute. Strength.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
Aerobic efficiency, and anaerobic performance.
- TFTim Ferriss
Got it.
- PADr. Peter Attia
So I guess we can unpack all of them, but stability is the ability to safely transfer load from the outside world to the body, and vice versa. Which sounds sort of like a, I don't know, kind of a, a soft ex-explanation. Um, an analogy that I really like using is that of a race car versus a street car. So what makes race cars so unique is that, and why, by the way, a race car that's got half the power of a street car will still knock its socks off on a track, is because the chassis and the tires of the race car are constructed in such a way that every bit of that power is making it to the road. So the analogy I like to think of is that the tires of a race car are like our feet, and stability really does begin with the feet. And most people, myself included, when I was starting, had horrible proprioception with our feet. Um, you know, we don't really know how to load our feet correctly, and a lot of that comes from the fact that we wear shoes all day. Um, your hands and your feet are actually very similar, and if you think about what you can do with your hands, how easily you can move them around, spread your fingers, sense d- pressure in different areas, most people can't do that with their feet, and that, that comes to, comes to bite you. So, um, as you think about how it moves up the, the sort of chain, um, a very common problem is, uh, uh, the... which I think accounts for probably more of the injuries that people experience, is this pattern where the pelvis is tilted forward, the ribs are flared up, the erector spinae muscles in the back are sort of locked short, meaning they're locked sh- like they, they're locked in concentric load, and the hamstrings are locked long, so they're locked in eccentric load.
- TFTim Ferriss
Yeah. It's how someone who's quite lean from a body fat perspective can still look like they have a potbelly-
- PADr. Peter Attia
That's right
- TFTim Ferriss
... with that anterior pelvic tilt.
- PADr. Peter Attia
Which actually, so, so you've asked me a question, and I think th- I can answer this with, there are really two things I'm excited about that pertain to exercise, and-
- TFTim Ferriss
Yeah, let's, hop in
- PADr. Peter Attia
... I'll, I'll go down this path, and then we'll come back to the other one. Um,
- 19:22 – 27:40
Posture
- PADr. Peter Attia
so what's the, what's the etiology of that position? Which I was the king of that position. Um, it's probably-
- TFTim Ferriss
What do you mean by etiology?
- PADr. Peter Attia
Like, where d- what drives that?
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
Why would a person show up with that posture of-
- TFTim Ferriss
Mm
- PADr. Peter Attia
... ribs flared up, pelvis tilted forward, back tight, hamstrings tight and long?
- TFTim Ferriss
Besides wearing six-inch stiletto heels.
- PADr. Peter Attia
[laughs] Yeah.
- TFTim Ferriss
No.
- PADr. Peter Attia
Which I never wore. I mean, I wore them sometimes, but I don't often wear them.
- TFTim Ferriss
You're in good company.
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
J. Edgar Hoover and all. [laughs]
- PADr. Peter Attia
Continue. So it probably starts with lousy respiration, and, uh, and I'm not exactly sure why that's the case, but I, I think somewhere along the way, we stop learning, or we stop breathing correctly into our abdomen, right? So we, instead of breathing the way we should breathe, which is the diaphragm should go down, the abdomen should come out, the pelvis should actually fill with pressure, we tend to breathe using ex- so that's the, those are the primary muscles of respiration is the diaphragm. We start using accessory muscles like the pec and the pec minor, and we kind of lift the chest up. That is a very common pattern of respiration, and I think it's that lifting of the chest that is what's bringing the rib cage up. And when that happens, the body is a little bit out of balance, uh, meaning your center of mass shifts forward. And the body senses that, and in an effort to prevent you from falling forward, it's basically tightening those erector spinae muscles. It's, it's pulling you into balance again. But in doing so, it's creating this downstream problem in the hamstrings, which is they're just, they're locking. And if there's another thing I've become really obsessed with, it's hamstring control, which is different from hamstring strength. Um, a lot of people, myself included, can have very strong hamstrings. I used to have incredibly strong hamstrings if you put me on a machine and made me do something in isolation, but I could never recruit them. So, uh, a simple exercise to demonstrate this, which Beth Lewis had me do for the first time maybe two and a half or three years ago, was laying on your back with your knees up and your feet down, so you're sort of in a back position, knees up, you know, feet on the surface of the ground. And without letting your back tilt into a huge, you know, make a huge dome underneath it, so while keeping your lower back flat-
- TFTim Ferriss
Lower back flat
- PADr. Peter Attia
... can you, with one leg, pull very, very hard back to your butt and feel your hamstring tense? So that is a very specific manner of recruiting hamstring strength. And believe it or not, I couldn't do that withou- while keeping my back down. My back w- I would arch like a cat if I tried to do that. There were many more of these types of exercises, but it was through this type of very deliberate, you know, starting on my back and then learning to do hamstring recruitment while standing and while feeling pressure in my feet that really allowed me to get back to deadlifting with a feeling of safety that I'd never really experienced. 'Cause I used to deadlift so heavy when I was young and basically got away with using my back to deadlift, which is obviously not what you wanna do. And then I just started having nagging injuries as I got older, so by the time I was in my mid-40s, I'm deadlifting, and it's like, oh, my SI joint would bug me, and after I'd finish, my back would just feel tight. Um, so it, it sort of, you know, w- what, age sort of, uh, exposes your deficiencies, and eventually everybody's going to sort of pay a price for this. Some people do these things naturally better than others, so I think there are some people who can kinda go their entire life lifting heavy weights without having to pay much attention to this stuff, but, you know, I certainly wasn't one of them.
- TFTim Ferriss
Does that type of training that you're describing, that progression, kind of starting back from the foundation or the fundamentals, does that have a particular name?
- PADr. Peter Attia
The, there are a couple different schools of thought that have been implemented into this training, one of them being dynamic neuromuscular stabilization, or DNS, which is heavily focused on this ability to find the breath and generate, uh, you know, this concentric abdominal pressure, so creating a cylinder inside the abdomen as opposed to, like, an upside-down triangle where you have some pressure up here but none down here. And then another school of thought that's been heavily influential here has been something called Postural Restoration Institute, or PRI, and that's, that's really the one that has focused on this idea of how do you correct what from the side looks like this, right? You know, sort of pelvis down, ribs up, and how do you fix that position? And, and, um, again, it's, it's, it's hard because it requires fixing everything from the feet to the neck.
- TFTim Ferriss
Hmm. How much of a contributor, if at all, do you think extended sitting is to that configuration with the kind of flared ribs up and anterior pelvic tilt, if any?
- PADr. Peter Attia
I, I think it probably is, um, and, and probably for a couple of reasons. You have to sort of think about it as the positive and the negative, right? So one drawback of sitting is that you're not active, so it's, it's simply the removal of active time that is a problem. And I think the other problem with sitting is it is simply harder to generate, um, intra-abdominal pressure, and it's easier to just rely on these accessory movements of respiration to lift up. So, you know, I, if, I think I've said this once before, like, if I could be tsar for a day, you know, I'd go back to kids when they're in school and, you know, have them in standing desks or squatting. Those would be your two positions, right? So you either, you're kind of squatting to do work or you're standing to do work, but you're not sitting in the types of chairs that we sit in.
- TFTim Ferriss
I think I have an idea for a, uh, complimentary short-form podcast for you, which is just called Tsar for a Day. [laughs]
- PADr. Peter Attia
[laughs]
- TFTim Ferriss
Five-minute, five-minute commandments from Tsar Attia.
- PADr. Peter Attia
Yep.
- TFTim Ferriss
Uh-
- PADr. Peter Attia
And more, more barefoot time. That's another thing, right? You know, with my first two kids, I wasn't so aware of this when they were young, and now with my youngest, who's almost four, like, I study this guy like he's, like, the master. His, his movement patterns are simply unbelievable, which of course all four-year-olds should be. I just never noticed it before. But the manner in which he moves and lifts himself and reaches for things and sits around, it's incredible. It is, it is such a spectacle to behold. Uh, so you know, if, if you, if you spend more time watching your children... And that's, you know, DNS is, is modeled on exactly that, right? DNS basically says... It, it, it grew out of, um, something called the Prague School in Czechoslovakia, which was originally, um, looking at ways to take children with cerebral palsy and teach them how to move again by realizing that what CP had robbed them of was a lot of the developmental movement patterns that occur in the first two years of life. And once they started to realize you could actually take these kids and retrain their neurologic system to do things in a more functional way, that you could actually do this as a form of rehab, and then ultimately a form of prehab-
- TFTim Ferriss
Hmm
- PADr. Peter Attia
... which is sort of how I like to think of it now, so.
- TFTim Ferriss
I've seen, uh, I don't know how much of this is public, but incredible results, uh, from a, a trainer, also world record holder, or former world record holder in Olympic weightlifting, Jerzy Gregorek, working with a number of, uh, clients or patients with cerebral palsy using very incremental, uh, movement rehabilitation and training. I mean, the, the, the before and after differences are staggering, and it's, it's, it's... I mean, I speaks to probably my ignorance of cerebral palsy, but just never was even within my, like, conceptual schema that that would be possible. It's very exciting to, to see, so, um, speaking of exciting.
- 27:40 – 29:55
Zone Two training
- PADr. Peter Attia
so the other thing on exercise, to get back to your question about the metabolic stuff, is, you know, about three years ago, I was becoming more and more interested in this idea of Zone Two training, uh, which has a very technical definition and then we can explain proxies for it. But the definition of Zone Two is the highest level of output you can produce while keeping lactate below two millimole. So-
- TFTim Ferriss
Mm-hmm
- PADr. Peter Attia
... um, lactate is a byproduct of anaerobic metabolism. So when we're sitting here at rest, our lactate level's probably one, if we're metabolically healthy. There are some people who sit around at rest higher than two. Um, but if anybody's done lactate testing knows, you know, as you start exerting yourself more and more, your lactate will rise. And, you know, peak levels in highly trained individuals can reach above 20 millimole, and that's accompanied by remarkable discomfort, actually. So, um, I've always done lactate training when I was, you know, being an athlete, which I haven't been in forever. Um, but I was never focused on this aspect of it. I was always focused on something called lactate threshold and peak lactate. So peak lactate, for me, was kind of a marker of just how much pain I could endure, and lactate threshold was a marker of the highest amount of output I could produce, um, for relatively short races. Um, like, you know, meaning short for me would be, like, half an hour or something like that, so knowing my lactate threshold was important for that stuff. But this Zone Two stuff is way below that, right? Zone Two is, by definition, your all-day pace. It's basically at a lactate level of two, you should be able to go all day, 'cause that's the, that's the level at which you do not net accumulate, so you're producing, but you're not accumulating.
- TFTim Ferriss
Right.
- PADr. Peter Attia
And so it's the rate at which clearance equals production, and you stay at that level of two.
- TFTim Ferriss
So does that training fall into the aerobic efficiency category?
- PADr. Peter Attia
Yes, exactly.
- TFTim Ferriss
[upbeat music] Just a very quick note to say that we really nerded out on Zone Two training with Peter. We got deep into the rabbit hole. It got very, very dense, also actionable, but I moved that section to the end of the episode. So if you wanna check that out later, just continue listening. Now, back
- 29:55 – 40:10
Diets, fasting, nutrition
- TFTim Ferriss
to the show. [whooshing sound] So you mentioned fat utilization or the ability to use fat as a, as a substrate. Are there things, and specifically what's coming to my mind, such as fasting or intermittent ketosis, that help you to use fat in such a way that it transfers to Zone Two training? Is there any crossover, I suppose?
- PADr. Peter Attia
Yeah. Well, there's no question that, you know, ketosis by its very definition is a nutritional state that forces your body to utilize fat. Um, and depending on how much you're intaking, some of that fat could be endogenous. So again, exogenous is the fat that you put in your body, so what fat you eat is exogenous. The fat stores that we have are endogenous. There's a bit of a, I think, just a misunderstanding around ketosis. I think a lot of people assume it is automatically a weight loss diet or a fat loss diet, but of course, that's not necessarily true. It's only a fat loss diet if you use your endogenous fat stores.
- TFTim Ferriss
Also turns out a pound of fat has a lot of calories. [chuckles]
- PADr. Peter Attia
Yeah. So, um, you know, I could gain weight on a ketogenic diet if I ate enough, right? Now, the, the advantage of ketogenic diets for most people is that they're quite satiating, and you don't want to eat endless amounts, uh, in the way that if you went on the all Dorito diet, which I've also pioneered.
- TFTim Ferriss
[chuckles]
- PADr. Peter Attia
I've got experience with the all Dorito diet, and, uh, turns out you can eat a lot.
- TFTim Ferriss
[chuckles]
- PADr. Peter Attia
Uh, the all licorice D- I used to work at a video store when I was in high school called Movies & Munchies.
- TFTim Ferriss
Yeah. [chuckles]
- PADr. Peter Attia
And, you know, it was owned by my friend's-
- TFTim Ferriss
It's a video store plus dispensary. [chuckles]
- PADr. Peter Attia
Yeah. And they didn't, they just didn't care how much I ate.
- TFTim Ferriss
Yeah.
- PADr. Peter Attia
And I would literally eat the pound of Twizzlers, like, you know, they came in that pound-
- TFTim Ferriss
Oh, my God
- PADr. Peter Attia
... maybe the pound and a half.
- TFTim Ferriss
It was huge.
- PADr. Peter Attia
It was like the biggest bag of Twizzlers.
- TFTim Ferriss
You could take out, like, a mugger with this bag of Twizzlers. Yeah.
- PADr. Peter Attia
Yeah, yeah, yeah, exactly. Like, it's a weapon, and if, if any reasonable group of four people went to a movie, they'd have a hard time finishing one, but I would easily throw that down, plus the really big bags of Doritos, plus a really big bag of popcorn, plus God knows what else. Like, that was routine for the night.
- TFTim Ferriss
[chuckles]
- PADr. Peter Attia
Just disgusting. Easily 4,000 or 5,000 calories of junk food three nights a week was my staple.
- TFTim Ferriss
So if we look at the opposite of that, fasting, has y- have you changed your mind or had, uh, any insights since we last spoke or come to any different conclusions related to fasting?
- PADr. Peter Attia
Yeah. I mean, I think-
- TFTim Ferriss
Because you've done, I mean, for the record, you've done, you've done a lot of fasting. I mean, you have a lot of experience doing-
- PADr. Peter Attia
Right
- TFTim Ferriss
... fasts of many different lengths, including, well, I don't know what the longest fast is that you've done. What would you say?
- PADr. Peter Attia
Probably 10 days.
- TFTim Ferriss
10 days, yeah.
- PADr. Peter Attia
Um, yeah. I think that, you know, one thing that I absolutely learned through fasting, uh, is the, the ep- the enormous importance of strength training throughout a fast. It's very easy. You're gonna lose muscle mass when you fast. You have to accept that. So the question is, how do you minimize that damage? How do you lose as little f- muscle mass as possible? And, um, strength training daily during a fast has become an important part of that. But when you look at time-restricted feeding, which is, or people call it intermittent fasting, although I don't, I don't like that term very much. I think time-restricted makes more sense when you're just talking about, you know, 16 or 18 hours. Um, I, I, I'm, I'm really starting to see a lot of people who do that excessively and who aren't necessarily training correctly. They lose weight, but they're losing muscle more than they would wanna see. And, you know, we just had a patient who we did a DEXA scan on last week, um, and it was probably the first one we've done in 18 months on him. And in that 18-month period, his body weight had not changed. Maybe he was a bit lighter, actually. He might've lost four pounds. But his body fat was so high, I almost fell off my chair. And he doesn't look chubby, right? But he's, he, it's, it speaks to how much muscle he's lost. So he, his body fat went from about 18% to 30%.
- 40:10 – 44:36
“3 levers” framework
- TFTim Ferriss
on the DEXA note, about, I don't what know, a year and a half or two years ago, uh, I recall a conversation with a DEXA technician who said to me, "Over the last 12 months, I've seen many cases of people coming in who are n- newly avowed intermittent fasters who have had their body composition flip," basically. I mean, like, not necessarily flip, but the, uh, they've had massive jumps in their percentage body fat. And I, I put that on social as a, as a note, not to, not to say that all people who do time-restricted feeding experience this, and it was, uh, hilarious and also, uh, frustrating to see how many religious zealots there are around intermittent fasting, who were just like, [laughs] "Bite thy tongue," you know? "Bite-
- PADr. Peter Attia
Wait, wait, but you said that according to this tech that they got better intermittent fasting, or worse?
- TFTim Ferriss
No, they got worse.
- PADr. Peter Attia
Oh, they got worse.
- TFTim Ferriss
There, there were many-
- PADr. Peter Attia
So, but it, it, it met with what I'm describing.
- TFTim Ferriss
It's exactly, it's exactly compatible with what you're saying.
- PADr. Peter Attia
Yeah, yeah.
- TFTim Ferriss
Uh, but there was a lot of resistance to the idea that that would even be possible, right? Uh, which I, which I found really interesting. More social commentary than anything else. Um-
- PADr. Peter Attia
A- and I, I think it just speaks to sort of why I don't like talking about nutrition very much, because it, it does lend itself to politics. Not literally, but it's sort of the politics, religion ethos, which is whatever you're eating is obviously the only thing. And, um, I guess I'd just encourage people to be much more attuned to all of the tools, right? So caloric restriction, dietary restriction, time restriction, right? You've probably heard me go on and on about my framework, the three levers. Um, always pull one, sometimes pull two, occasionally pull three, never pull none. So time restriction, what we were talking about, restricting when you eat, but otherwise not restricting how much or what. Dietary restriction, uh, is restricting some of, like, some of the content in what you eat, so not eating carbs, not eating wheat, not eating meat, something like-
- TFTim Ferriss
Not eating Doritos.
- PADr. Peter Attia
Right. [laughs] Um, not eating sugar. Those are all forms of dietary restriction. Um, and then caloric restriction is restricting the amount. And so if you are never pulling one of those levers, which means you're eating as much as you want, whenever you want of w- of, you know, whatever, anything you want, any time, how much, whatever, that's called the standard American diet.
- TFTim Ferriss
SAD.
- PADr. Peter Attia
Yeah, [laughs] the SAD.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
And we've been running a very good natural experiment on that for 50 years, and the data are in. So it turns out that less than 20% of the population, probably less than 10% of the population, is genetically robust enough to tolerate the SAD. Um, so it's a great piece of data. Like, there are people out there who can, you know, eat KFC, and Doritos, and pizza anytime they want, and they're generally okay, to a first-order approximation. I would add that we don't really know the answer to this question because we don't have super granular data at the population level. But notwithstanding that, at least at the surface level, it appears that 10% of the population are largely, um, you know, immune to the SAD. But for the rest of the 90% of us schmucks, uh, whi- whi- which I'm certainly in that camp, the SAD is lethal, and so you've got to come up with a way to, you know, escape the gravitational pull of the SAD, and that's why I think having these three levers at your disposal is, is the key. And yeah, I think that what happens is people get so into the camp of their lever, like it's all time restriction or it's all dietary restriction. Not too many people are in the all calorie restriction group. Um, there's a whole calorie restriction society, and there, so there certainly are people that are in that camp. Um, but it's usually the first two camps that have the, the most zealots.
- TFTim Ferriss
Levers. I was waiting for the Canadian to come out.
- PADr. Peter Attia
[laughs]
- TFTim Ferriss
Love, always love those levers. And I think-
- PADr. Peter Attia
Ah, sorry. I'm sorry.
- TFTim Ferriss
Sorry. I'm so sorry.
- PADr. Peter Attia
I'm so sorry for that.
- TFTim Ferriss
Process. Process.
- PADr. Peter Attia
Just the process. [laughs]
- TFTim Ferriss
[laughs] And I also think I, I said bite thy tongue. I don't practice my older English much. I think it's thine tongue, but I'm sure the internet will correct me.
- 44:36 – 46:38
Muscle loss when fasting
- TFTim Ferriss
Quick, uh, tactical question, and then I want to ask you about any research or studies that have been interesting to you that have come out since we last spoke. Uh, is it effective or have you tested using small amounts of branched-chain amino acids to mitigate the muscle loss during what we would otherwise consider fasting? And d- and does that affect, does that also, if it has any effect, uh, lessen the benefits of the fast?
- PADr. Peter Attia
It depends on what you're doing the fast for. I think if you're doing the fast for weight loss, then the answer is absolutely knock yourself out with branched-chain amino acids during strength training, because from a caloric perspective, they represent such a-
- TFTim Ferriss
Negligible
- PADr. Peter Attia
... yeah, yeah, yeah. Like, even if you were to double up on, you know, my favorite BCAAs, which are Biosteel, you know, you're, what are you gonna get in there? 40 calories in two servings, right? So not an issue. If you're doing the intermittent fasting with, call it the hope of achieving some amount of the early signatures of autophagy, then I would say that it probably is counterproductive because the amino acids that you use in exercise are exactly the ones that are the most potent stimulators of mTOR. And the whole purpose of fasting, at least in the short term, is to give mTOR a rest. It's to take away that which it senses, and it is the most potent sensor of leucine-
- TFTim Ferriss
Mm
- PADr. Peter Attia
... which is the most important branched-chain amino acid.
- TFTim Ferriss
Yeah. So if, so if, if I could dumb that down for myself, uh, if you are interested in the longevity benefits of fasting, aside from just getting to healthy body composition, you should not take the branched-chain amino acids.
- PADr. Peter Attia
It seems to me it would... I mean, I can't say anything with certainty, but it seems counterproductive.
- TFTim Ferriss
Yeah.
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
Got it.
- 46:38 – 1:11:01
Psilocybin and MDMA
- TFTim Ferriss
All right, studies. Any papers or studies that you found interesting?
- PADr. Peter Attia
Oh my God.
- TFTim Ferriss
Since [laughs]
- PADr. Peter Attia
So many. Uh, um, there's a lot. Um-
- TFTim Ferriss
If you had to, if you had to cherry-pick a few.
- PADr. Peter Attia
Well, look, I think the recent New England Journal paper that you and I have talked about, um, is very interesting, comparing Lexapro to psilocybin. Um, I, I wrote about it recently, and, um, my little diatribe basically said, I think the paper was, in some ways, misinterpreted. Um, it was positioned as a negative trial, though I saw it as anything but a negative trial. Uh, maybe just for background-
- TFTim Ferriss
Could, could we zoom out just for a second-
- PADr. Peter Attia
Yeah
- TFTim Ferriss
... and give people an overview of the objective or the hypothesis of, of the study?
- PADr. Peter Attia
Yeah. The question that was being tested was, is, um, an intermittent dose of pure synthetic psilocybin, um, more effective, I think is the way the question was posed, than the top-tier SSRI for, uh, patients with depression?
- TFTim Ferriss
Yeah.
- PADr. Peter Attia
So Lexapro is a relatively new SSRI, very well tolerated.
- TFTim Ferriss
Escitalopram?
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
Um, it does have sexual side effects. That's its most common side effect. Um-
- TFTim Ferriss
That's true of other SSRIs as well.
- PADr. Peter Attia
Absolutely, yeah. SSRIs are, are known for having sexual side effects. Some of them also come with, you know, incredible amounts of somnolence, incredible amounts of weight gain. Lexapro-
- TFTim Ferriss
Somnolence, sleepiness
- PADr. Peter Attia
... sleepiness, yeah. Um, Lexapro seems to be relatively free of that for most people, which is why it's kind of more of a, a go-to drug. Comes in two doses, 10 and 20 milligrams. Generally, most people need 20 if they're gonna go to it, but you usually start people at 10, go to 20. Um-
- TFTim Ferriss
And this is a daily-
- PADr. Peter Attia
It's a daily drug
- TFTim Ferriss
... administration?
- PADr. Peter Attia
Yep. So, you know, the participants are divided into two groups. One group is given, um, Lexapro. Uh, let me think. I believe that they all started out at 10 milligrams for three weeks, and then were increased to 20 milligrams for three weeks, or maybe it was four plus four. I can't remember. It was a relatively short study. In the psilocybin group, the participants were giv- oh, they, by the way, as an aside, they were also given one milligram of psilocybin, um, which I, is an important point I should make.
- TFTim Ferriss
And if that word is unfamiliar to folks, so psilocybin is a molecule found in psilocybe mushrooms, also known as magic mushrooms. These are mushrooms that impart psychedelic effects at a sufficient dose.
- PADr. Peter Attia
We'll come to talk about that dose. So the subjects were all recruited knowing that they would get psilocybin no matter what, because that was an important recruiting tool. People wanted to be in a study where they were gonna get the psilocybin, and that's, that has to be taken into account from the standpoint of patient selection. So every trial has to be thoughtful about what type of people it's selecting, and are they representative of the population you're gonna want to extrapolate your results to. So I flag this to make the point that when you have a patient population that says, "I really, really wanna get psilocybin," and you say, "Okay, well, you're not gonna get necessarily the full dose. There's only a 50/50 chance you're gonna get the full dose, but you're gonna get some."
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
So you're either gonna get one milligram or 25 milligrams.
- TFTim Ferriss
Yeah.
- PADr. Peter Attia
And we'll put in context what those doses mean in a second.
- 1:11:01 – 1:28:42
Cholesterol and ApoB
- TFTim Ferriss
Uh, any other, any other studies, uh, that, that come to mind? Or you mentioned ApoB. I'm wondering if you have any thoughts on ApoB that you'd like to share.
- PADr. Peter Attia
Yeah. Certainly as it pertains to things where I'm evolving my thinking. I'm-
- TFTim Ferriss
And what is ApoB?
- PADr. Peter Attia
Yeah. It's probably worth explaining that before we do anything else. So most people have heard of cholesterol. Um, and most people are used to seeing a blood test where you would see your total cholesterol, LDL, HDL, and if the, if the lab is half decent, it would actually say LDL-C, HDL-C, non-HDL-C, VLDL-C. What does all that mean? So that means LDL cholesterol, or the cholesterol contained within LDL. HDL cholesterol is the cholesterol contained within LDL. So why do all these things even exist? So every cell in our body makes cholesterol. Um, it's an essential molecule for life. So if you don't have cholesterol, you're not going to live more than, you know, a few seconds. In fact, you'll die in utero, if we're gonna be blunt. So every cell makes this thing. It's, it makes up the cell membrane of every cell. It's what allows membranes to have fluidity and have transporters sitting across them. It's also the backbone for many of the hormones we make. Now, the problem is cholesterol is not water-soluble. So when you have something that's not water-soluble that needs to be transported through the body, which this does, because as I said, not every cell makes enough of it to meet their own needs, so there are net exporters and net importers of cholesterol, you have to have a system that can move it around. But just like if you tried to pour olive oil into a glass of water, you would quickly realize they don't mix, and similarly, you can't just move cholesterol through the bloodstream the way you can move things like glucose, sodium, potassium, things that are water-soluble. So glucose just travels through the bloodstream on its own, as does a ketone body, for example, but triglycerides, you know, have to be bound. Things that are fat-soluble have to be bound. So- Um, you know, Mother Nature invented something called a lipoprotein, which is a spherical thing that on the outside is water-soluble and on the inside houses these water-insoluble or what we call hydrophobic things, namely cholesterol ester and triglycerides. And these lipoproteins exist in two broad families, and the families are defined by the protein signature that wraps around them. So the two families are the ApoB family and the ApoA family. Technically, there's a subclass of the ApoBs. There's an ApoB 100 and an ApoB 100. But for the most part, anybody that's talking about ApoB is referring to ApoB 100. The ApoB 48 is only something called a chylomicron that is a sh- very short-lived lipoprotein that gets fat out of your gut. [lip smack] So let's put that guy aside for the moment, unless anyone wants to come back, and we'll do the advanced course on the weekend.
- TFTim Ferriss
[laughs] Okay, advanced course for the midi-chlorians.
- PADr. Peter Attia
[laughs]
- TFTim Ferriss
You nerds out there. All right. Continue.
- PADr. Peter Attia
So your, your ApoB family consists of very low density lipoprotein or VLDL, intermediate density lipoprotein or IDL, low density lipoprotein or LDL, and LP little a, who is the worst actor of the bunch, which is an LDL with another special lipoprotein wrapped around him called an ApoA or an apolipoprotein little a. [lip smack] Not ApoA. I should be really clear. It's apolipoprotein little a. You have to specify little a to not confuse it with the ApoA family. The ApoA family is the lineage of the high density lipoproteins. Okay. Most people know that HDL good, LDL bad, but that's a little overly simplistic. What we really mean to say is that HDLs do not cause atherosclerosis, LDLs do. But it turns out LDLs aren't the only thing that cause atherosclerosis. Anything with an ApoB on it causes atherosclerosis.
- TFTim Ferriss
And just, just to, just for the, for the, for the listeners, [chuckles] atherosclerosis meaning the buildup of plaque within the cardiovascular system, or how do you think of athero-
- PADr. Peter Attia
Yeah, it's the, it's the infla-
- TFTim Ferriss
... stiffening or inflammation?
- PADr. Peter Attia
It's the inflammatory disease of arteries that ultimately results in plaque formation and, in the worst case scenario, results in rupture of this plaque that leads to an acute thrombosis or an acute occlusion, and if it occurs in the wrong spot, that can be, um, fatal, instantly fatal.
- TFTim Ferriss
Got it.
- PADr. Peter Attia
So VLDLs stick around for long enough that if you have too many of them, they are atherogenic. IDLs are not really a problem because they just don't last that long, so the transit from VLDL to IDL and then IDL to HDL occurs qu- or to LDL is so quick that the IDLs are kind of irrelevant. LDLs, of course, are the majority of your ApoB concentration, unless you also have a lot of insulin resistance where you might have a lot of VLDLs or if you have a genetic condition that predisposes you to have too many of those. The IDLs, again, we don't really worry about those. The LDLs are the lion's share of your ApoB, and about one in eight to one in 12 people also have a very genetically high level of LP little a, and that also represents, um, uh, part of the ApoB concentration. So ApoB is a far superior measurement to LDL-C when trying to predict cardiovascular risk. So it is hands down the best biomarker we have for cardiovascular risk because it is the total concentration of all particles capable of inducing atherosclerosis. Now, atherosclerosis is multifactorial, so lots of things drive it. Inflammation plays an important role, and metabolic health plays a super important role, um, [lip smack] but we understand that lower ApoB is better. Where I think the tr- the data are becoming more and more clear is how low you can push this thing without unwanted effects and how much more benefit you can get. So there's always a concern, I think, and understandably so, that if you lower ApoB, you're lowering cholesterol. Because if you have fewer of the particles that carry cholesterol, you have less cholesterol floating around the blood. But what most people don't understand is that that's sort of like saying, "I'm gonna reduce the number of cars traveling over this bridge." Does that necessarily mean you're reducing the number of cars in the city? Not necessarily. So most of the cholesterol in your body is not in the lipoproteins rummaging around through your veins. Um, again, most of the cholesterol is still sitting inherently in the cells itself. So if you took a person's total cholesterol and it was 200 milligrams per deciliter and you lowered it, and, uh, by total cholesterol, by the way, at this point, I, I assume is straightforward to explain. It's the sum of all the cholesterol and all the lipoproteins, so the VLDL, IDL, LDL, LP little a, and HDL. If you bash all of those particles and take out all the cholesterol, that's what your total cholesterol is. If you took that number from 200 to 100, you would say, "God, that's a 50% reduction in your cholesterol." No, it's a 50% reduction in your serum cholesterol, which might be like a 5 to 10% reduction in your total body cholesterol. So that's one thing to keep in mind. The other thing to keep in mind is we are born with very, very low levels of cholesterol. So in a child, the ApoB concentration is probably in the ballpark of 30, 20 to 30 milligrams per deciliter. By the time we're adults, a level of 80 milligrams per deciliter would put you at the 20th percentile, meaning 80% of people would have a higher number than 80. What's the upshot of this? The upshot of this is there's no upside to having more ApoB, right? The, uh, the upside is in having that number be lower and lower and lower. But until recently, it wasn't clear how low you could drive it. And there was a, a, a type of drug that was developed about... Well, I mean, developed about 17, 18 years ago, but it bec- it, it became clinically available. Uh, I shouldn't say that, actually. It probably started development in about '05, so call it 16 years ago. Um, hit the market in 2014 or 2015, a class of drug called PCSK9 inhibitors, and they work, um, in a m- manner that's distinct from all previous drugs that lower cholesterol. They work by inhibiting a protein that degrades LDL receptors on the liver. And by inhibiting this thing that degrades them, you get more of the LDL receptors on the liver. It pulls more of the LDL recep- it pulls more of the ApoB-bearing particles out of circulation, um, mostly which are LDL particles, but also some Lp (a) particles. With these trials, we see people achieving levels of ApoB in the 10 to 30 range, um, with no side effects, no consequences. Furthermore, these drugs were developed when populations of people were identified who naturally had mutations in PCSK9 that rendered their PCSK9 ineffective. So this was basically a drug that was designed to mimic a genetic mutation found in people who, over the course of their lives, have no, um, increased risk of any disease and simply have a decrease in their risk of cardiovascular disease. In fact, their risk of cardiovascular disease is virtually nonexistent.
- TFTim Ferriss
Let me ask a silly question. How does, how does one find people who have such a mutation to track them?
- PADr. Peter Attia
Well, it started with the opposite. So there's a condition called familial hypercholesterolemia, uh, or FH for short, which are people who have very high levels of cholesterol and very high levels of LDL cholesterol, and by extension, very high levels of ApoB. And they're pretty easy to spot. Um, but it's a definition that is based on phenotype, not genotype.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
So it's genetic condition-
- TFTim Ferriss
Fascinating
- PADr. Peter Attia
... but it's one phenotype, but 3,000 or more genotypes, meaning there are thousands of different genetic mutations that lead to that. I think it was in the late '90s, one of those genetic pathways was identified as a hyperfunctioning PCSK9. So a group in Toronto identified PCSK9 and realized that these people had a hyperfunctioning version of this protein, and it was constantly degrading LDL receptors. And so they just couldn't clear the ApoB out of their circulation, and that's why they had sky-high LDL and total cholesterol. When that population was identified, the question was asked, which is: Is there a counterpart to them? And it turns out to be really easy to identify them because they're the opposite. These are people who don't take any medicine to lower their cholesterol, and they have levels like infants.
- TFTim Ferriss
Mm.
- PADr. Peter Attia
And then it was realized. And I remember actually reading that paper when it came out and being blown away and actually thinking, "There's no way they're gonna be able to do this with a drug." Um, but it turned out it was, it was actually pretty druggable. Um, it wasn't that hard to do, uh, and in many ways, it's a much cleaner drug than, say, a statin. Like statins, which are, despite all the public mayhem around it and the religious polarizing debates around statins, statins are really safe drugs. 10% of people have unwanted side effects and shouldn't take them, um, but they're very well-tolerated drugs. And in my mind, that's kind of a miracle when you consider what they do, which is they inhibit cholesterol synthesis. And when you think about how important cholesterol synthesis is, it's kind of amazing to me that that works without killing people. My hypothesis for this, by the way, is that statins occurred in nature. So the first statins were really copying something that was found in nature called red yeast rice. And as a general rule, I think things that came from nature tend to be a little safer. You know, psilocybin, um, rapamycin, metformin, some of my other favorite drugs. Um, but this, the, the method of, by which the PCSK9 works is, is just elegant 'cause it's really just targeting one protein with a, you know, with an antibody that makes it, um, harder for the LDL receptor to break down.
- TFTim Ferriss
Are there any benefits to lowered or low ApoB, uh, outside of cardiac risk, lowering cardiac risk?
- PADr. Peter Attia
Yeah, there actually is, and the-
- TFTim Ferriss
Or I shouldn't say cardio-
- PADr. Peter Attia
Yeah
- TFTim Ferriss
... cardiovascular risk.
- PADr. Peter Attia
Yeah, yeah, yeah. A-and, and that's sort of, um... I mean, I think we've known for, for a while that it also poses a benefit with respect to Alzheimer's disease, for sure. Um, and that's one of those things where I think one needs to be a little bit careful about never confusing population data with individual data, and it's why I think population data are fantastic, but every patient has to be completely assessed as an individual. So at the population-based data, for as long as we've had statins, we've known that lower ApoB or lower LDL-C means less risk of Alzheimer's disease. And if you think about some of the paths by which people get Alzheimer's disease, there's clearly a vascular path. So Alzheimer's disease is not a disease. Uh, in, in, in, just in the same way cancer is not a disease, singular. It's many diseases, not just tissue type, but even within tissue type. You know, within breast cancer, for example, you have different receptor profiles. The same within lung cancer, so. Or even just the mutation can render two cancers completely different animals. And similarly, Alzheimer's disease is a collection of lots of diseases with a final common pathway, but you can get there metabolically. You can get there through a vascular path. You can get there through an inflammatory path. Uh, there might even be an autoimmune path there. The vascular path is a big path, in my opinion, and therefore, anything that improves microvascular health, which statins do, should improve-
- TFTim Ferriss
Mm
- PADr. Peter Attia
uh, the risk of Alzheimer's disease. So there was something called the Mendelian randomization that was published, I think, like literally a week ago, and I'll explain what a Mendelian randomization-
- 1:28:42 – 1:56:30
Rapamycin and lifespan
- TFTim Ferriss
Let's jump to rapamycin since you, since you mentioned it, and, uh, we can give a very quick [laughs] idea on what rapamycin is. But since we last spoke, uh, more bearish, more bullish, and why?
- PADr. Peter Attia
Um, I am, I'm a bull.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
Dogecoin and Rapa.
- PADr. Peter Attia
[laughs]
- TFTim Ferriss
Diamond hands. All right.
- PADr. Peter Attia
[laughs]
- TFTim Ferriss
So, so what is rapamycin?
- PADr. Peter Attia
By the way, tell me, I mean, I know, I know what the diamond hands thing is, but what does it, where did it come from? Like-
- TFTim Ferriss
I have no idea.
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
I have no idea where diamond hands comes from.
- PADr. Peter Attia
Okay. I, I was like, "Did I miss that somewhere in my, in my reading?"
- TFTim Ferriss
In your, in your, in your econ classes? [laughs]
- PADr. Peter Attia
Yeah, yeah, yeah.
- TFTim Ferriss
No.
- PADr. Peter Attia
So anyway.
- TFTim Ferriss
I don't think so.
- PADr. Peter Attia
Okay.
- TFTim Ferriss
So what is rapamycin?
- PADr. Peter Attia
So rapamycin is a drug that, um, is a naturally occurring, uh, antifungal agent made by a bacteria that was discovered on Easter Island, uh, back in the 1960s.
- TFTim Ferriss
Otherwise known as Rapa Nui.
- PADr. Peter Attia
Right. Rapa Nui is the correct name for Easter Island, and the bacteria Streptococcus hydroscopicus, which was discovered there by a group of explorers, um, explorers is maybe the wrong word, but people doing sort of medical prospecting. Uh, a group from Montreal, I believe, in call it 1966. They took a bunch of soil and dirt back from Rapa Nui to the lab in Montreal, where it sort of sat there unattended to for about five years. Uh, a chemist, a very astute chemist by the name of Saran Seagal-
- TFTim Ferriss
Great name
- PADr. Peter Attia
... yeah, he started mucking around-
- TFTim Ferriss
Related to Steven Seagal? No.
- PADr. Peter Attia
[laughs]
- TFTim Ferriss
Different. [laughs]
- PADr. Peter Attia
Uh, and no ponytail, unfortunately. Um, so Saran did some really interesting chemistry, isolated the compound, and noticed it had these really remarkable properties, which was it was the most potent antifungal agent he had ever seen, or the world had ever seen, frankly. Um, at the time, uh, as his son Ajit tells the story, um, who I've gotten to know a little bit, he felt he had basically come onto the biggest blockduster, blockbuster cure, cure for athlete's foot the world was ever gonna know. And right about that time, the company he worked for closed its Montreal headquarters, actually laid many people off, ordered the destruction of all non-viable compounds, and shipped him off to New Jersey. Um, in one of the greatest acts of scientific fortuity, he did not follow orders-
- 1:56:30 – 2:01:00
Sauna benefits
- TFTim Ferriss
All right, what else? Any of the three categories really, if, if, if there's something-
- PADr. Peter Attia
I know. Something else I've changed my mind on.
- TFTim Ferriss
Yeah.
- PADr. Peter Attia
I'm way, way, way more bullish on sauna than I have ever been before.
- TFTim Ferriss
Oh, yeah. Tell me more.
- PADr. Peter Attia
I used to be in the camp of sauna feels great, it maybe even helps you sleep a bit better, um, that's probably about it. Like, there's no way you're gonna really live longer because you're in a sauna. [lips smack] And while truthfully, we don't have really great prospective data, um, or, sorry, I should say we have good prospective data, we don't have good randomized data. I think this is one of those things where the burden of evidence in the non-randomized data is so strong, it's becoming hard to ignore. So most of the research on this subject has come out of Finland, and-
- TFTim Ferriss
The sauna lobby
- PADr. Peter Attia
... surprise, yeah.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
Um, and so there's the obvious issues with this, right? The people who can afford to sauna are by definition gonna have more time on their hands, more disposable income, probably more education, like all of the standard, uh, things. On top of that, if you're gonna choose to sauna because you believe it's healthy, what else are you doing because you believe it is healthy? I mean-
- TFTim Ferriss
Right
- PADr. Peter Attia
... so, so, you know, if, if the data showed that sauna versus non-sauna was like a 5% improvement in mortality, it would be hard to get that excited about it. But when you look at the largest published series on this, you see a benefit in all-cause mortality, a relative absolute, pardon me, a relative risk reduction of 40% and an absolute risk reduction of like 18%. Those are-
- TFTim Ferriss
Those are high numbers
- PADr. Peter Attia
... those are ridiculous numbers. And that's when you, um, are comparing someone who own a, like saunas four to seven times a week-
- TFTim Ferriss
I was gonna ask you-
- PADr. Peter Attia
Yeah, so what's the dose and frequency of sauna? Yeah
- TFTim Ferriss
... what's the, yeah, what's the dose and frequency, and what do you believe the minimum effective dose to be? Kind of like the Zone Two training, you described what it is, and then you said bath, let's do three hours a week.
- PADr. Peter Attia
Yeah, so just to get to, just-
- TFTim Ferriss
I do four times 45
- PADr. Peter Attia
... yeah, just to get to the punchline, I, I think based on the research, the MED is four sessions, 20 minutes, 80 degrees Celsius.
- TFTim Ferriss
Four sessions times 20 minutes-
- PADr. Peter Attia
At
- TFTim Ferriss
... 80 degrees Celsius.
- PADr. Peter Attia
Yep.
- TFTim Ferriss
Oh, you. Fahrenheit, what's the conversion there? I should know better. I should-
- PADr. Peter Attia
Uh, it's about 175 Fahrenheit.
- TFTim Ferriss
175 Fahrenheit. Got it. Dry, wet.
- PADr. Peter Attia
There's much more literature on dry.
- TFTim Ferriss
Okay.
- PADr. Peter Attia
You know, I s- I actually had a call with a patient this morning, and this topic of saunas came up, and she asked if she could substitute steam rooms and such, and I said, "We just don't know 'cause we don't have the data." Um, so the, you know, the precautionary principle would say if you have access to a dry sauna, that's where we have reams and reams and reams of data, so it's probably where it goes. But look, if you think about what the mechanism of action is-
- 2:01:00 – 2:04:30
Preferred Zone Two method
- TFTim Ferriss
Preferred method for zone two training? Seems like you do most of your work on a bike.
- PADr. Peter Attia
I do. I like the bike. It's just my body is so much more efficient on a bike than anything else.
- TFTim Ferriss
Do you have a preferred stationary bike, or do you-
- PADr. Peter Attia
Yeah, I, I do. I ride my bike, like my road bike, on something called a Wahoo KICKR.
- TFTim Ferriss
Wahoo KICKR. [laughs]
- PADr. Peter Attia
Which is awesome, like hands down, super-
- TFTim Ferriss
If someone doesn't have a road bike-
- PADr. Peter Attia
Then I, my favorite stationary bike is the Keiser.
- TFTim Ferriss
K-A-I-S-E-R?
- PADr. Peter Attia
Yeah, K-A-I-S-E-R, I believe. And I think Keiser makes such a fantastic, uh, spin bike.
- TFTim Ferriss
Amazing. You wanna do one more change your mind about, or one more excited? You can, uh, dealer's choice.
- PADr. Peter Attia
Yeah, I'm, I'm pretty excited about GLP-1 agonists.
- TFTim Ferriss
Tell, [laughs] tell me to. I don't even know what that means. Tell me, Peter.
- PADr. Peter Attia
All right, so GLP-1 agonist, glucagon-like peptide one. They also go by GLP-1 RAs, so glucagon-like-
- TFTim Ferriss
Receptor
- PADr. Peter Attia
... peptide one receptor agonist Okay, so glucagon is a hormone. It's made by the liver, sort of opposes the action of insulin. It's a, um, it's a hormone that, um, produces satiety, um, and, uh, can regulate blood glucose levels. So-
- TFTim Ferriss
Regulate meaning it's catabolic?
- PADr. Peter Attia
Lowers, lowers blood glucose.
- TFTim Ferriss
Lowers blood glucose.
- PADr. Peter Attia
Yeah. It, it secretes insulin, actually. It results in secretion of insulin to lower blood glucose.
- TFTim Ferriss
I see.
- PADr. Peter Attia
So-
- TFTim Ferriss
Got it
- PADr. Peter Attia
... these are a group of drugs that have been around for quite some time. Also, uh, kind of a, a, a high choice in people with type 2 diabetes. Um, a trial came out, [clicks tongue] I wanna say 2014, showing that one of these drugs was actually also pretty good for weight loss in non-diabetics.
- TFTim Ferriss
Hmm.
- PADr. Peter Attia
It didn't get a lot of traction. The effect size was, was reasonable, but it wasn't great. I looked at it quite a bit, 'cause I remember at the time I had a patient who, whose weight was really recalcitrant. It just wasn't clear what it was gonna take to get her to help, help her lose weight, and I certainly am not a fan of stimulants for weight loss. Um, you know, drugs like phentermine can be somewhat effective, but they can also have their side effects and be somewhat habit-forming. And we had sort of noodled this and, and eventually we ended up trying this drug. It didn't really have that much of an effect, and I, I kind of sort of put it aside for a while. Um, until about six or seven months ago, [clicks tongue] I was talking to someone who had an early line of sight into a trial that was gonna be published, and they said, you know, they'd been using it clinically, a newer version of this drug. Um, it's called semaglutide. The, um, [clicks tongue] trade name is Ozempic. Um, and they said, "Yeah, you've gotta see what this drug can do." Like, so the drug, the dose that's given for people with diabetes is one milligram once a week. So it's an injectable drug.
- TFTim Ferriss
Hmm.
- PADr. Peter Attia
So it's, it comes in a little pen. You, you know, shoot it in your gut or your leg once a week, one milligram.
- TFTim Ferriss
Is it intramuscular or s- uh-
- PADr. Peter Attia
Sub-
- 2:04:30 – 2:11:32
Effectiveness of Semaglutide
- PADr. Peter Attia
And then sure enough, there was a study that was published, um, probably a couple of months ago looking at semaglutide in overweight and obese people without diabetes, and the weight loss was through the moon.
- TFTim Ferriss
Hmm.
- PADr. Peter Attia
I mean, it was, you know, we're talking like 20% weight loss.
- TFTim Ferriss
Holy shit. [laughs]
- PADr. Peter Attia
Um, completely durable as long as you're on the drug.
- TFTim Ferriss
Yeah.
- PADr. Peter Attia
So then it begs the question, what happens when you come off the drug? Um, we haven't seen fully what that looks like yet. I mean, I think we need to see what those studies look like. I mean, my, my thinking of this, we've now put a lot of patients on this drug. Um, I mean, a lot is relative, but you know, maybe, maybe 12, 15 patients we've put on this drug. Some people can't tolerate it because of the nausea. So-
- TFTim Ferriss
Nausea?
- PADr. Peter Attia
Yeah. I mean, that's definitely one of the side effects, which-
- TFTim Ferriss
How often is it administered?
- PADr. Peter Attia
Once a week.
- TFTim Ferriss
Once a week. Uh, is the nausea transient, or is it-
- PADr. Peter Attia
Yeah, it tends to fluctuate how far you weigh or you... Well, so if you inject it on a Sunday, and then, you know, usually by the next Saturday the symptoms are gone, but then when you hit yourself on that Sunday, Sunday, Monday, Tuesday, you'll be a bit more nauseous. Now again, that's, so it's transient across the week, but it also-
- TFTim Ferriss
Yeah
- PADr. Peter Attia
... seems to be transient over time. So the, the dose in the study was 2.4 milligrams, so, you know, two and a half times higher than you're doing it in people with type 2 diabetes. But, um, you don't start people at that dose. You'll start them at half a milligram for a few weeks, then one milligram, then one and a half, then two, et cetera. Um, but basically we haven't seen any patient who can tolerate the drug d- that does not lose weight.
- TFTim Ferriss
Hmm.
- PADr. Peter Attia
Um-
- TFTim Ferriss
Have, have any cycled off? In which case, I mean, obviously behavior matters a lot and calories matter a lot, but-
- PADr. Peter Attia
Yep
- TFTim Ferriss
... do you see a greater-
- PADr. Peter Attia
No
- TFTim Ferriss
... rebound than you would anticipate otherwise?
- PADr. Peter Attia
No. And they don't seem to regain all the weight they lost. Now, my biggest concern, and it w- I mean, this, I was so fascinated by this, uh, before the study came out. We actually did a whole journal club just on this study and went, like, stupidly nerdy on this drug. Um, the biggest concern I would have is, is a drug that lowers glucose but raises insulin such a good idea?
- TFTim Ferriss
Hmm. Yeah.
- PADr. Peter Attia
Um, and also it flies in the face of how you would lose weight in that situation, right? It, it seems to not be entirely clear why would that result in weight loss unless the increase in insulin along with the glucagon-like peptide are reducing appetite. But what we've discovered in experimenting with a lot of our patients, by experimenting I mean just doing a lot of blood tests before and after, is while it probably slightly increases your fasting insulin level, it's also clearly increasing muscle insulin sensitivity because postprandial insulin levels seem to be down. And I would bet, though it was not done in this study-
- TFTim Ferriss
Postprandial meaning post-meal
- PADr. Peter Attia
... after meal. I would bet that if they had looked at 24-hour insulin secretion, which you can do by collecting 24 hours of urine and measuring C-peptide-
- TFTim Ferriss
Hmm
- PADr. Peter Attia
... which is-
- TFTim Ferriss
I didn't know that
- 2:11:32 – 2:14:06
Resources and recommendations
- TFTim Ferriss
Are there any other resources or recommendations for folks who want to improve their ability to separate fact from fiction, hype from reality when it comes to headlines, media, studies, and so on? I mean, not, not to get to Peter Attia level, but to get to the point where they just have a better ability to separate signal from noise with this kind of thing.
- PADr. Peter Attia
You know, there's a good newsletter that I subscribe to out of the University of Indiana. Um, it's called the, I think it's called Metabolomics in Energetics or Metabolism in Energetics. It's like a weekly newsletter that comes out on Fridays, and it's, you know, it's pretty detailed, but one of the sections is always headline versus study.
- TFTim Ferriss
Oh, that's great.
- PADr. Peter Attia
And that's, that's always a cute one, 'cause every week you get to see... They just pick one example, because of course there's a billion examples every week-
- TFTim Ferriss
Yeah
- PADr. Peter Attia
... of how the headline says something, and it turns out to have nothing in common with the study. Now, that's not exactly the question you've asked, but it is a good illustration of just how, basically, just because you, if you read something in the media, it's, you should just assume it's in, it's, it's being taken out of context and it's incorrect. Um, and unfortunately, I, I, I wish I had better answers on-
- TFTim Ferriss
Well, it'd be like if you saw a headline that said, "Eating nubbins increases risk of colorectal cancer by 100%," but if the chance is 1 in 10 billion people and it goes to 2 in 10 billion people-
- PADr. Peter Attia
It's a great-
- TFTim Ferriss
... doesn't, doesn't mean you should pay attention to it.
- PADr. Peter Attia
That's right, and that's a great ex-
- TFTim Ferriss
Not to discredit your nubbin theory.
- PADr. Peter Attia
A- a- and but that's a great example of always knowing absolute risk versus relative risk. That's exactly-
- TFTim Ferriss
Right
- PADr. Peter Attia
... that's exactly like the kind of stuff we talk about in studying studies, is-
- TFTim Ferriss
Yeah
- PADr. Peter Attia
... never pay attention to relative risk without knowing absolute risk as well, and things like that, so.
- TFTim Ferriss
Yeah. Peter, I think it might be time for us to prepare for our, uh, prandial adventure. [laughs] That's probably not the word you use, but to have our meal. Uh, to have our, to have our [laughs]
- PADr. Peter Attia
Our preprandial exploration.
- TFTim Ferriss
Our preprandial exploration of, uh, various, various cacti. Is, is agave considered a cacti? Well, I guess, what is mezcal actually made from? Is it agave?
- PADr. Peter Attia
Um, well, certainly tequila's agave.
- TFTim Ferriss
I know it's like a campfire in your mouth, but that doesn't tell us much about-
- PADr. Peter Attia
Yeah, I know
- TFTim Ferriss
... the botanical origins. I know sotol is different. Have you had sotol, as a side note?
- PADr. Peter Attia
No.
- TFTim Ferriss
It's a plant, or I should say it's a be- also, it's a beverage. Maybe it isn't a plant, but it's only found in a few parts of Texas and Mexico, and it's sort of in between tequila and mezcal.
- PADr. Peter Attia
Speaking of Texas,
- 2:14:06 – 2:18:39
Texas—the good, the painful
- PADr. Peter Attia
can I tell you the only thing so far about Texas I'm not fond of?
- TFTim Ferriss
Uh, scorpions in your kitchen?
- PADr. Peter Attia
Uh, eh, they, uh [laughs]
- TFTim Ferriss
[laughs] That, that-
- PADr. Peter Attia
I've only found six
- TFTim Ferriss
... that was, that was this morning [laughs] in my household.
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
We took care of it. It was fine.
- PADr. Peter Attia
Um- It's the cactuses when I'm out in the bush.
- TFTim Ferriss
Mm.
- PADr. Peter Attia
So when I was out-
- TFTim Ferriss
[laughs] What are you doing out in the bush?
- PADr. Peter Attia
Well, when I was out doing that precision shooting, uh, a couple months ago-
- TFTim Ferriss
Yes [laughs]
- PADr. Peter Attia
... they were, like-
- TFTim Ferriss
Training for your counter sniper operation
- PADr. Peter Attia
That's right. So we had, like, mats down on the ground, and we're laying on our mats, and we're, you know, shooting off in the distance, and I, I vaguely remember someone saying, "Stay on your mat."
- TFTim Ferriss
Oh, God. Oh, God. [laughs]
- PADr. Peter Attia
And, um, so at one point I'm, like, loading my magazine, and I kinda rolled off the mat-
- TFTim Ferriss
Oh
- PADr. Peter Attia
... and, you know, loaded it and, and was shooting. And then, like, that day we're driving home and I'm like, "God, why does my butt hurt so much, and why does my leg hurt so much?" And, you know, by the time I got home, I realized I was just full of these little microneedles.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
And, you know, it went through my pants or anything. And I mean, this is how you know your wife really loves you, because, like, I had to give her a set of tweezers to literally start yanking these needles out of my butt and my leg, and I actually still have some there. Three months later, I still, I can still feel some of the ones that broke beneath. And, and so I'm going on this hunt in, um, about three weeks, and it's, I mean, my first time hunting axis deer here in Texas, and one of the things that the guide who's taking me said is, "You, you gotta make sure your shoes, uh, won't get poked, like, the cactuses won't go through your boots."
- TFTim Ferriss
So you're not gonna wear your ninja socks for this one?
- PADr. Peter Attia
Yeah, no.
- TFTim Ferriss
[laughs]
- PADr. Peter Attia
This will not be a barefoot hunt. But aside from the cactuses, man.
- TFTim Ferriss
Yeah, yeah.
- PADr. Peter Attia
Yeah.
- TFTim Ferriss
All good in the Republic of Texas. I have a shirt. Maybe I'll get you one of these. You might have seen it. It says, has a, has a big flag, Texan flag on it, and it says, "Most likely to secede."
- 2:18:39 – 2:34:32
Zone Two deep dive
- TFTim Ferriss
Could you just briefly explain what efficiency means within the aerobic efficiency and then come back to the Zone 2 training?
- PADr. Peter Attia
Yeah. It comes down to basically substrate usage. So in, um, in aerobic activity, um, you can use glucose or fat. Those are basically the two fuels that, um, the body with oxygen can turn into ATP. So aerobic, most people will recognize, means with oxygen, and anaerobic means without oxygen. So when you're not demanding much energy of yourself, and energy, of course, we talk about is ATP, so ATP is the currency for energy. Um, when your body isn't demanding much energy, you can make ATP using glucose or using fatty acids, and it's a similar process, but obviously different because they're different molecules. So glucose gets turned into something called pyruvate, and that happens in the cell but outside of the mitochondria. And then the pyruvate gets shuttled into the mitochondria, where it undergoes a process, uh, known as the electron transport chain, where a whole bunch of chemical reactions occur that basically generate a gradient of electrons in the inner membrane of the mitochondria that's ultimately used, um, to produce carbon dioxide and water and a boatload of ATP. With fatty acids, it's a little different. Uh, fatty acids get broken down into smaller chunks of fatty acids that have two carbons, called acetyl-CoA, and the acetyl-CoAs get fed into the mitochondria and undergo the same sort of process. So- Um, what's nice about that is you have the ability to use both fuels. But when energy demands start to climb, so when you are asking more of yourself, when you're now running or when you're walking up a flight of stairs or doing anything that now the body's saying, "Hey, I need more and more ATP," that glucose system is the first one to cave. So the glucose system, when you turn the glucose into pyruvate, it basically says, "I don't have enough oxygen to run this through the mitochondria to do what I need. I'm going to instead turn pyruvate into lactate," which yields some ATP, but a pittance compared to what it could do. So, you know, pyruvate into lactate will generate one-sixteenth the ATP that it would if it went into the Krebs cycle, which is horrible, but it's like any port in a storm, right? It's like, I don't have a choice. As a, as a side note, everybody tends to think that lactate is what causes the soreness when you're doing that. It's, it's actually not the lactate.
- TFTim Ferriss
Is it hydrogen?
- PADr. Peter Attia
It's the hydrogen ion that accompanies the, the, the lactate 'cause lactate is acidic. So you don't actually feel anything from the lactate, and lactate itself is actually a pretty remarkable fuel. The brain, there's e- emerging evidence that the brain actually likes lactate as a fuel, and the liver can turn it back into glucose pretty easily. But nevertheless, it's inefficient, right? It's a horrible way to turn your hydrocarbon into ATP, um, and it does come with this problem of being self-limited. So the efficiency speaks to the longer you can use the mitochondria, the better. And this Zone Two characteristic is really one of the most remarkable ways to separate and differentiate people with different e- degrees of metabolic efficiency. So, um, Inigo San Millán and George Brooks did a study that I talked about at length in one of the AMAs.
- TFTim Ferriss
Did you say Cesar Millan? No, I'm kidding. [chuckles]
- PADr. Peter Attia
Oh. [chuckles]
- TFTim Ferriss
The dog trainer.
- PADr. Peter Attia
Yeah, yeah, yeah.
- TFTim Ferriss
What, what were the names again?
- PADr. Peter Attia
Inigo-
- TFTim Ferriss
Oh, okay
- PADr. Peter Attia
... San Millán and George Brooks.
- TFTim Ferriss
Got it.
- PADr. Peter Attia
Uh, Inigo's been a guest on my podcast as well. They did a study looking at three cohorts of people: professional cyclists, fit people, and people with Type 2 diabetes.
- TFTim Ferriss
Just real quick, how did they define fit?
- PADr. Peter Attia
Um, I don't remember exactly, but it would be, like, people who exercise a certain number of hours a week who were pretty fit.
- TFTim Ferriss
Mm-hmm.
- PADr. Peter Attia
These were people that were probably exercising 10 hours a week or something to that effect. Um, so, so not just kind of like weekend warriors.
- TFTim Ferriss
Yeah, 10, 10 hours a week is not trivial.
- PADr. Peter Attia
No, no, not at all, right? And what they looked at was what were their lactate curves, um, on a bicycle, and at what point did they reach that two millimole level? And, you know, it's just a staggering difference. Um, so all of them would u- ultimately achieve high lactates, admittedly very different powers, right? The fitter you are, the more power you generate before you hit that peak lactate. The people with Type 2 diabetes were reaching this critical threshold at something in the vicinity of 80 to 100 watts. Um, so 80 to 100 watts on a bike. If you don't know what that feels like, um, it's hard to explain what that would f- I, I wish I had a good conversion for what that feels like. Uh, that's not a lot of effort. Uh, I mean, I mean, I guess for someone who spends any time on a bike-
- TFTim Ferriss
Flat ground, slight incline.
- PADr. Peter Attia
Yeah, flat ground, no wind, going 13 or 14 miles an hour.
- TFTim Ferriss
Got it.
- PADr. Peter Attia
Uh, maybe less. Um, which amounts to about 1.2 watts per kilo, 'cause you always wanna normalize these things to body weight. So 1.2 watts per kilo, one watt per kilo in that vicinity. The, the reasonably well-trained average, you know, not average, reasonably well-trained person, um, was hitting that number at closer to 150 to 170 watts, uh, putting them pretty comfortably in about the 1.7, 1.8 watt per kilo range. So, you know, significantly higher than people with Type 2 diabetes. And the professional cyclists were hitting that mark in the vicinity of 320 to 360 watts, and of course, they're even lighter, so they're hitting that number at a staggering four watts per kilo.
- TFTim Ferriss
What was the total duration of the assessment?
- PADr. Peter Attia
It's typically done, you, you know, unlike a ramp test where you're quickly, quickly changing, you, you typically do long ramps. So, you know, 15 minutes, check lactate, 15 minutes, check lactate, or 10 minutes would be about the minimum.
- TFTim Ferriss
Do you think those results would have looked different had the muscle groups involved been different? Had it been, uh, like a hand bike or something like that? I guess I'm wondering if there's any localized effect just given the training of the cyclists.
- PADr. Peter Attia
Yeah, it's possible. Um, and, and certainly there's a, you know, there's an efficiency that comes from doing the thing that you're being tested on. Typically, lower body exercises are the way to do this because we have so much muscle mass there. When we have patients do their Zone Two, we basically recommend three things. You know, a bike, a rowing machine, or a treadmill are probably the best ways to, to get that. And it doesn't have to be running. I mean, when I do-
- TFTim Ferriss
Now, to get, you mean to assess or to also train?
- PADr. Peter Attia
Both.
Episode duration: 2:34:53
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