Dr. Peter Attia — Interview on Life-Extension, Ultra-Endurance, and More

1. 0:00 – 2:37

   Breakfast banter and opening skit before the show begins

   1. TFTim Ferriss0:00

      Uh, so Mr. Peter, tell me about your very, very boring and repetitive breakfast

   2. PADr. Peter Attia0:07

      Uh, it usually starts with, uh, nothing. Um, and then I usually do a second course usually 'cause I'm a little hungry, and I'll have a little bit more nothing. And then, um, I usually just, I top it off with a bit of nothing

   3. TFTim Ferriss0:19

      [laughs] Okay, hold on. Optimal minimal living At this altitude, I can run flat-out for a half mile before my hands start shaking. Can I ask you a personal question? Now we're receiving a project from Anna. What if I give you all of it?

   4. PADr. Peter Attia0:32

      I'm a cybernetic organism with living tissue over metal endoskeleton.

   5. TFTim Ferriss0:36

      The Tim Ferriss Show. This episode of The Tim Ferriss Show is brought to you by 99designs. 99designs is the world's largest online marketplace of graphic designers, and I have used 99designs for years, including to get cover concepts for The 4-Hour Body, which went on to become number one New York Times, number one Wall Street Journal. It was a huge hit. And here's how it works, and you can check everything out, including some of my competitions. You can see these book covers and so on at 99designs.com/tim. Whether you need a logo, a car wrap, a web design, an app, a thumbnail, a T-shirt, whatever, you go to 99designs.com, you describe your project, and then within a week or less, you have tons of designers around the world who compete for your business and submit different ideas and designs and drafts. You have an original design that you love or you pay nothing. It is fantastic. I have used it. I have mentioned it before, including in The 4-Hour Workweek as a resource. Check it out, 99designs.com/tim, and if you use that link, you'll be able to see what I've done on the platform. You will also get $99 as an upgrade for free, which will get you more designs, more submissions, so check it out. ONNIT, ONNIT and I go way back. Check them out at onnit.com, O-N-N-I-T.com/tim. You can see a bunch of my gear. I've used their products for many years. When I moved into my new place, I got rid of 75% of everything that I own, but if you go to my garage, you will find kettlebells from ONNIT. You will find battle ropes from ONNIT. You will find maces, clubs. I know it sounds like a medieval torture chamber, and it kinda looks like that, but it's for torturing myself. I also use their chewable melatonin to knock myself out when traveling or reset my clock. They've got just about everything. So if you wanna see some of my favorites, check out onnit.com, O-N-N-I-T.com/tim.

2. 2:37 – 4:52

   Tim introduces Peter Attia and frames the conversation topics

   1. TFTim Ferriss2:37

      This is Tim Ferriss, and welcome to another episode of The Tim Ferriss Show, special holiday edition. I am celebrating this December with some reflection, looking back at what I've done this year or not done, and reassessing, trying to figure out how to do things that are bigger, better, badder in the coming year. And one of the most impressive people that I'm contemplating thinking of emulating in this coming year is Peter Attia, MD. He is the guest for this episode. And while I sip on my guayasa tea, which is from the Amazon, maybe a shrub tree, I have no idea, but it's something that'll get you stopped in customs and perhaps, uh, have your body cavities searched if it's in a big gallon Ziploc bag. Don't ask me how I know that. Uh, he is one of the few people I have on speed dial for advice, and Peter's a very impressive guy. He is the president and co-founder of the Nutrition Science Initiative, NUSI, uh, which is-- can be thought of as the Manhattan Project for nutrition. I'm an advisor to that group. He co-founded it with Gary Taubes, who wrote Good Calories, Bad Calories. But prior to all of that, he has an incredible range of experience. He worked at McKinsey & Company. Before that, he spent five years at Johns Hopkins Hospital as a general surgery resident, where he was the recipient of many different prestigious awards, and he, uh, also authored comprehensive reviews of general surgery. He spent two years at the NIH, the National Institutes of Health, as a surgical oncology fellow at the National Cancer Institute, and he earned many different degrees. I'm not gonna go into all of them, but MD from Stanford, uh, mechanical engineering and applied mathematics degrees. The guy is a stud, and he is also an ultra-endurance athlete, so he puts theories into practice. He also does horrible, horrible things to himself in the name of self-experimentation, just like me, that we will get into in this interview. So without further ado, uh, and it does get a little into the weeds. It gets a little dense in a few areas, and I implore you to just bear with it. There are lots of gems here, so please meet Peter Attia. [upbeat music] Peter, welcome to the show. Thank you for joining me on this afternoon.

   2. PADr. Peter Attia4:50

      Thanks for having me, Tim.

3. 4:52 – 8:42

   How NUSI was formed and why nutrition science needs different funding and risk tolerance

   1. TFTim Ferriss4:52

      And I have, have thought about our original introduction. I think it had to be through Gary Taubes. Is that right? Was that the, was that the first contact?

   2. PADr. Peter Attia5:03

      Yeah. I think Gary introduced us about two and a half years ago.

   3. TFTim Ferriss5:06

      And to, to give people a little bit of context, because there are many things I'd love to delve into, uh, not the least of which is your, your sort of medical and scientific pedigree, but also your, uh, your similar DNA, uh, that is, I feel like we're kind of cut from the same cloth, that we have a certain lack of self-preservation in self-experimentation, or at least interest in [laughs] pushing things, um, to s- kind of an obsessive or a very clearly obsessive degree. So I wanna jump into both of those. But, uh, the project that first brought us together was NUSI. So maybe you could give people just a little bit of background on, uh, on what NUSI is, and of course, I ended up becoming an advisor, but, uh, the, the Manhattan Project for Nutrition as it has been called, um, maybe you can tell people a little bit about it.

   4. PADr. Peter Attia5:57

      Yeah. It's exactly how we got introduced, Tim. And, and, uh, it's, it's basically, uh, it's an organization that Gary and I founded, um, in 2012, uh, with the idea of trying to do ... nutrition science at a level that, that currently isn't doable in the existing, um, funding and, uh, political is the wrong word, but sort of, uh, risk atmosphere of how, how nutrition science is done. So fundamentally, we argue that, and I don't think you'll find much pushback on this, there are two main impediments to doing exceptional work in nutrition science. The first is that, um, while in aggregate there's a lot of money out there, in terms of doling it out to specific studies, it's, it's, it's shockingly low. Um, and secondly, and perhaps more importantly, there really isn't an appetite to ask questions that are directly counter to the conventional point of view. Um, and so we felt that there are in fact alternative hypotheses about the role of diet and disease that do need to be asked. They could be wrong. I mean, it's, it's entirely likely that, uh, or certainly plausible that, that these ideas that we have could be incorrect, but, um, they deserve a shot. They're certainly not our ideas, right? I mean, we're just sort of champions of them. And, uh, if the worst thing that happens is you spend time and resources demonstrating that what's currently believed to be true is true, um, that's, that's a pretty limited downside when you consider that the upside is if you demonstrate the opposite, that some of these things in fact are incorrect, the payoff's enormous.

   5. TFTim Ferriss7:26

      Right. And I think that oftentimes perhaps people view, uh, being a scientist as something that is, is restricted to a very rarefied echelon of highly trained people, and granted there are people who are, are very well-trained for science, but it r- it's really on some level about finding hypotheses worth disproving, right? And sort of asking the uncomfortable questions. So I think by political, I, I think political is an appropriate term in a lot of instances, and to, to frame it a different way, the reason I was attracted to NUSI is that, uh, many of the studies out there are either very poorly designed, they are, uh, they conflate correlation with causation. I mean, you see this all the time. Uh, they're misinterpreted by the media, and then they're oftentimes funded by very, very biased parties who sometimes have a profit motive. So the idea that you could raise, uh, how- whatever the dollar amount was, but you had, uh, your, your anchor backer was the Arn- the Arnold family, if I'm not mistaken.

   6. PADr. Peter Attia8:32

      That's correct, John and Laura Arnold.

   7. TFTim Ferriss8:34

      These, uh, massively, uh, I suppose his, his background is as a, uh, energy trader, I believe, but, uh, c- please correct me if I'm wrong.

   8. PADr. Peter Attia8:41

      That, that's correct.

4. 8:42 – 12:10

   Why disagreement among researchers matters: avoiding “bolt-on” explanations

   1. TFTim Ferriss8:42

      You have this, this money coming in that is independent, unbiased to fuel studies, uh, designed and conducted by an eclectic collection of the brightest scientists in the US and probably beyond, many of whom disagree with one another, and I think that's... Maybe you could just comment on that because I think it's a really important point.

   2. PADr. Peter Attia9:05

      Yeah. When, when Gary and I, uh, started talking about this idea back in probably the spring to summer of 2011, um, we, we realized that we actually both had a pretty similar point of view on what the likely dietary triggers of metabolic disease were. In other words, why is it that in one generation or certainly two generations we've seen an epidemic of disease, uh, that, that previously didn't really exist? Um, we also agreed that the current state of the evidence, that which we found most compelling, was technically not really sufficient enough to change the rules of the game, to change the way medical advocacy groups and physicians and even the government would, would, you know, suggest people go about eating. And so we felt that what was missing was science. But to your point, um, you know, to get a whole bunch of people that agree with you, that all, you know, that share your point of view to do the work i- is not a powerful way to go about doing it. Part of the opportunity here is, um, working with people who have different points of view about things, um, not just because that's allowing you to draw from a broader pool, you're now actually accessing everybody as opposed to a subset, um, but because a really good scientist at the end of the day is defined by several things, but one of them is when confronted with conflicting data, you know, they c- they, they face it, right?

   3. TFTim Ferriss10:25

      Mm-hmm.

   4. PADr. Peter Attia10:26

      Um, as opposed to sort of coming up with what we call ad hoc hypotheses, which are bolt-on hypotheses meant to support the original hypothesis in the face of evidence contrary.

   5. TFTim Ferriss10:35

      Right. So the, the... I want to give people perhaps a snapshot on your background because I, I think, I think science can be intimidating, but ultimately, uh, if, if you look at a lot of the, say, amateur scientists throughout history, uh, oftentimes the, the motives were very personal, right? So they lived in a, a place where, uh, you know, smallpox was a, an epidemic, and they noticed that milkmaids didn't get smallpox, and they hypothesized they could take sort of pus or whatever from cows and inject their own families.

   6. PADr. Peter Attia11:09

      [laughs]

   7. TFTim Ferriss11:09

      I mean, these crazy fucking ideas that ended up having a gr- a high degree of validity. And, uh, you of course, I mean, you, you re- you earned your MD from Stanford. You have a mechanical engineering and applied mathematics degree from Queen's University, and, uh, you have McKinsey, you have Johns Hopkins, John Hopkins Hospital as a surgery resident, uh, lots of awards and so on. But, and we, we can dig into that a little bit further, what are your obsessions from a performance standpoint? I was half joking earlier when I said lack of self-preservation, but it, it is kind of literal in the sense that, uh, it's possible to try to optimize health to the point where it's, it's in your best interest to just kind of sit in a metal box and, uh, absolve yourself of interacting with anything in life, and I think that you maximize your performance at the same time. So what are some of your obsessions in that realm at the moment or interests?

5. 12:10 – 16:00

   Athletic obsessions: from boxing training to ultra-distance swimming

   1. PADr. Peter Attia12:10

      Well, gr- uh, growing up, Tim, you know, I grew up in Canada. Um, and so obviously hockey was sort of the most important sport for any good Canadian kid growing up. But actually pretty early on, around the age of 13, um, my interest actually shifted towards, uh, boxing and martial arts, and that became really the focus of my life. And, you know, I never really did it in moderation. So even in high school, I was sort of training six hours a day, uh, very, very hard. Even though in amateur boxing it's only three rounds, I was always thinking about, you know, the next step, which was being a professional, and of course at the time that's, you know, 12 rounds of boxing. So everything I did was geared towards, you know, I had to run 10 to 15 miles in the morning, not just 4. I had to jump rope for 30 minutes, not just 15, and had to spend this many hours sparring each day. And so my, my foray into the under- or the c- or the, you know, my care about the body's performance always came through the lens of performance, right?

   2. TFTim Ferriss13:05

      Mm-hmm.

   3. PADr. Peter Attia13:05

      So it was how does, you know, what I, how do, how, how does the way I train or how does the way I eat impact my performance initially in a boxing ring?

   4. TFTim Ferriss13:14

      Mm-hmm.

   5. PADr. Peter Attia13:14

      Now, at the time it was highly crude, right? In fact, I suffered from the issue that I'm sure a lot of 14-year-old boys suffered from, which we'd all kill to have that problem again, which is I actually couldn't gain weight, right?

   6. TFTim Ferriss13:25

      [laughs]

   7. PADr. Peter Attia13:25

      I mean, I was ... You know, I started my career at 127 pounds. By the time I was 16, I was a solid middleweight, which is 160 pounds. But as y- as you may know from, from your experience, most people live 10 pounds above their weight class and then come down to it.

   8. TFTim Ferriss13:41

      Right.

   9. PADr. Peter Attia13:41

      But, you know, I was only 4% body fat, so I actually lived and fought at about 158 pounds. Um, and to, to keep that weight on, I would eat about 6 to 7,000 calories a day. Uh, uh, just to give you an example of lunch, right? Because it was the one meal I can really remember.

   10. TFTim Ferriss13:58

       [laughs]

   11. PADr. Peter Attia13:58

       It was an entire loaf of bread.

   12. TFTim Ferriss14:00

       [laughs]

   13. PADr. Peter Attia14:01

       Which is 14 pieces of bread, so that was 7 sandwiches, um, with a 2 liter jug of orange juice.

   14. TFTim Ferriss14:09

       [laughs]

   15. PADr. Peter Attia14:09

       And a, um, I would ... And then at the cafeteria, I would buy a plate of french fries and, like, some other nastiness. And, like, that was lunch every day in high school, and yet, you know, I had a 27-inch waist and, you know, no fat on me. Uh, in part not just because I was exercising six hours a day, I think more importantly because we're very metabolically different when we're 14-year-old boys than when we're 40-year-old boys.

   16. TFTim Ferriss14:33

       [laughs]

   17. PADr. Peter Attia14:34

       Um, so if you fast-forward, uh, I don't know how many years, um, you know, athletic stuff has always been important to me. The sport has shifted, you know? Um, it went f- you know, by the time I was in my early 20s, the obsession switched away from, um, boxing into other things. And, and, um, more recently in my 30s, it, the, the obsession became swimming, ultra, ultra long distance swimming. Um-

   18. TFTim Ferriss14:58

       How long is ultra long distance swimming?

   19. PADr. Peter Attia15:00

       Y- yeah, it's kind of a fuzzy definition. I think most people define ultra long as anything over 16 miles.

   20. TFTim Ferriss15:06

       Mm-hmm.

   21. PADr. Peter Attia15:07

       Um, but I think that's somewhat arbitrary. It's sort of like one of those things, like, you know it when you see it, right?

   22. TFTim Ferriss15:11

       [laughs]

   23. PADr. Peter Attia15:11

       Like, hey, is this, is this one mile a river?

   24. TFTim Ferriss15:13

       Like pornography. [laughs]

   25. PADr. Peter Attia15:14

       Yeah, exactly. Right?

   26. TFTim Ferriss15:15

       [laughs]

   27. PADr. Peter Attia15:15

       Is this one mile swim across the river ultra long? Not really. Is that 25 mile swim long? Yeah, that's ultra long.

   28. TFTim Ferriss15:21

       [laughs]

   29. PADr. Peter Attia15:21

       Um, and-

   30. TFTim Ferriss15:22

       What's the longest swim that you've done?
6. 16:00 – 20:09

   From endurance training to metabolic syndrome: testing, markers, and a wake-up call

   1. PADr. Peter Attia16:00

      Um, and yet interestingly, my weight is getting higher and higher and higher. And I went from sort of being, you know, 170 pounds to 205 pounds, and the, uh, composition of that weight wasn't a, you know, wasn't what I wanted, right? It wasn't like I was gaining all this muscle. I mean, I was getting fat, and the blood tests showed that I was basically pre-diabetic. So all of a sudden, the dietary strategy-

   2. TFTim Ferriss16:25

      What were the indicators that you looked at?

   3. PADr. Peter Attia16:27

      Um, you do something called an oral glucose tolerance test, which is, uh, you, you, they draw your blood and then you drink this horrible, nasty drink of glucose, and then they measure your insulin and glucose levels an hour later and then again two hours later.

   4. TFTim Ferriss16:41

      Got it.

   5. PADr. Peter Attia16:41

      Um, coupled with other standard blood tests like your triglycerides and something called a hemoglobin A1C, which measures the amount of blood sugar that's basically sticking to your red blood cells.

   6. TFTim Ferriss16:52

      Is it fair to say hemoglobin A1C is sort of a running three-month average of your fasting glucose, or is that completely scientifically un-

   7. PADr. Peter Attia17:00

      No, it's, it's actually pretty close

   8. TFTim Ferriss17:01

      ... obvious. Okay.

   9. PADr. Peter Attia17:02

      It's not fasting. It's a three-month, it's basically a three-month running average of your aggregate glucose level.

   10. TFTim Ferriss17:07

       Aggregate glucose.

   11. PADr. Peter Attia17:07

       Yeah.

   12. TFTim Ferriss17:07

       Got it.

   13. PADr. Peter Attia17:08

       Yeah.

   14. TFTim Ferriss17:08

       Okay.

   15. PADr. Peter Attia17:08

       Yeah.

   16. TFTim Ferriss17:08

       Cool. Not the interim.

   17. PADr. Peter Attia17:09

       Um, yep, yep. So, so, so anyway, uh, basically all of these tests were pointing in the wrong direction. I had something called metabolic syndrome. Um, and again, I think there's a lot of people that find themselves in that situation. I, you know, to your question about what's the personal motivation, I think what pissed me off was, and I remember saying this to my wife, I said, "You know what pisses me off, is I'm working too hard to be in this situation," right?

   18. TFTim Ferriss17:34

       [laughs]

   19. PADr. Peter Attia17:35

       Like, it's one thing if you're sitting on the couch eating Doritos all day long, but my diet was actually much cleaner as a 35-year-old than that french fry, sandwich eating kid in high school. Um, obviously it still wasn't the right diet, but the point is, I was busting my ass to be fit and healthy and watch what I eat, and, you know, frankly, I just got aggravated beyond words. And, you know, I mean, I, we joke about it now, but at the time I literally said to my wife, like, "I'm gonna go get a gastric bypass."

   20. TFTim Ferriss18:05

       [laughs]

   21. PADr. Peter Attia18:05

       And she was like, "You are the most ridiculous human being that's ever lived."

   22. TFTim Ferriss18:09

       [laughs]

   23. PADr. Peter Attia18:09

       "I mean, we're gonna literally have to talk about our marriage if that's what you're considering at the w- at, at the weight of 205 pounds."

   24. TFTim Ferriss18:15

       [laughs]

   25. PADr. Peter Attia18:16

       I actually did go and see the top bariatrician in the city of San Diego. And [laughs] it's kind of a weird story, because even though I was like obviously overweight, I was the thinnest person in the waiting room by a long shot, right?

   26. TFTim Ferriss18:32

       Yeah.

   27. PADr. Peter Attia18:32

       And it sort of put in perspective, like, Peter, you think you've got problems? I mean, these people each weigh 400 pounds.

   28. TFTim Ferriss18:38

       Right.

   29. PADr. Peter Attia18:38

       And when I went up, when it was my turn to go and see the doctor, the nurse took me up to the scale and weighed me. And like we get on the scale and I'm like 210, and she's like, "Oh, this is fantastic." Like-

   30. TFTim Ferriss18:47

       [laughs]
7. 20:09 – 24:39

   Ketones 101: why the body makes ketones and how nutritional ketosis works

   1. TFTim Ferriss20:09

      Uh, but what, what are, what are synthetic ketones and why might people care about them?

   2. PADr. Peter Attia20:14

      Well, I think to explain it, I probably have to spend a minute explaining what ketones are biologically, or what we call-

   3. TFTim Ferriss20:19

      Yes

   4. PADr. Peter Attia20:19

      ... endogenous ketones. So, um, if you think back to what our ancestors were doing up until, you know, a few hundred years ago, or certainly a few thousand years ago, you know, we were basically often going 24 hours or longer without food. Um, and that was just the nature of how things worked, right? And when you're in the hunter/gatherer, uh, uh, mindset, that, that's your life. Now, um, the, the human body has only really evolved to store a finite amount of glucose. Uh, and there's only two places we store glucose. One is in the liver, one is in the muscles. Um, and it's only that stash in the liver that's accessible by the brain, because the glucose that gets stored in the muscle can't leave the muscle. It, it circulates within the muscle. So we have this organ, the brain, which, you know, weighs maybe 2% of our overall body weight, but probably accounts for 20% of our body's metabolic demand, and on top of that, it ordinarily functions exclusively on glucose. And so you have this problem, which is you have an organism that is wildly dependent on glucose, and we can only store a fraction of what we need. We can only store about one day's worth. So-

   5. TFTim Ferriss21:26

      About 400, 400 grams, like 1600 calories?

   6. PADr. Peter Attia21:28

      It really depends on the size of the person, but yeah.

   7. TFTim Ferriss21:30

      Right.

   8. PADr. Peter Attia21:31

      That's, that's probably about right for average. And remember, most of that, by the way, is not accessible to the whole body.

   9. TFTim Ferriss21:38

      Right.

   10. PADr. Peter Attia21:38

       It's... Yeah, so, so the, the trick that we evolved was, um, rather than make glucose out of protein, which is a pretty easy thing to do, the problem with that is if you wanna make glucose out of protein, you have to break down muscle. And the last thing you wanna do when you're out there trying to find your next meal is lose muscle at, in, at the expense of getting glucose for your brain. So what if there was a way we could get the brain to use fat, right? That's, that's the problem that needed to be solved. And the solution was a beautiful one, right? Which is we can break down fat, of which even the leanest hunter-gatherer had days and days, if not months of fat on their body. What if you could break that fat down in the liver into another type of molecule distinct from glucose that the brain specifically could actually utilize as fuel? And that's where ketones enter. And so what, what our bodies do when prolonged fasting occurs, and by prolonged, I really mean it even begins at 24 hours of fasting, is we start breaking down our own sources of fat. We start making this thing you referred to, beta-hydroxybutyrate. That, not to get too geeky on it, but beta-hydroxybutyrate and another member of that family called acetoacetate, they exist in an equilibrium, and these things get shuttled into the Krebs cycle, which I think your readers, your readers will be familiar with. Um, and it basically becomes another substrate for making ATP. And so all of a sudden, and George Cahill, who is sort of a luminary in this field, passed away a few years ago, but George Cahill is one of the sort of the, the leading godfathers in metabolism at Harvard University. Um, he did some legendary experiments, um, in the '50s and '60s where they, you know, they had subjects that they would starve for seven to 14 days and just measure glucose levels and ketone levels, and you'd think that after 14 days of not eating, a person would be, you know, mentally foggy, not well, and it turned out it was just the opposite, right?

   11. TFTim Ferriss23:29

       Right.

   12. PADr. Peter Attia23:29

       After a couple day lull, and you know this personally, Tim, because you've done these long fasts.

   13. TFTim Ferriss23:34

       Right.

   14. PADr. Peter Attia23:34

       After a couple days of hell, it's actually the reverse, right? You sort of get sharp-

   15. TFTim Ferriss23:38

       You feel amazing. Yeah.

   16. PADr. Peter Attia23:38

       Yeah, you feel unbelievable. And, and what Cahill showed was, you know, what fraction of the brain's energy was coming from those ketones. So okay, so that's relevant. That's starving. But look, outside of the odd, you know, let's do a one week a year fast sort of thing, how does that play into something beyond that? Well, the other way you can achieve ketosis, though not to the same extreme, is through something called nutritional ketosis, which is restricting the one dietary component primarily that restricts ketone formation and keeping at a minimum the other one that also restricts it, and those are carbohydrates and proteins respectively. And so if you eat a diet that has very little carbohydrate in it and only a modest amount of protein, um, and the rest of it of course made up from fat, you can also generate ketones. Now, to your question, it turns out that you can drink or, you know, consume in some fashion, but they're all typically liquid, you can drink these ketone molecules directly, and that's what we call these exogenous or

8. 24:39 – 30:53

   Exogenous (synthetic) ketones: forms, brutal taste, and what they’re supposed to do

   1. PADr. Peter Attia24:39

      supplemental ketones, and they come in multiple different forms. They basically exist in as a beta-hydroxybutyrate ester, a beta-hydroxybutyrate salt, and an acetoacetate diester. Um, and I've tried all of these things, and I can safely say-

   2. TFTim Ferriss24:57

      Why don't you t-tell people-

   3. PADr. Peter Attia24:58

      Yeah

   4. TFTim Ferriss24:58

      ... why don't you recount your first experience [laughs] consuming these?

   5. PADr. Peter Attia25:02

      Yes. So the first, the first one I tried was the betae- beta-hydroxybutyrate ester, which a very good friend of mine, um, uh, sent me, and I had been told these things taste horrible, that I had talked to two people who had consumed them before, and these are stoic dudes. Like, these aren't-

   6. TFTim Ferriss25:19

      [laughs]

   7. PADr. Peter Attia25:20

      ... you know, this isn't like a six-year-old kid, right? This is, like, stoic military dudes who said, "Oh man, that's the worst-tasting stuff on earth."

   8. TFTim Ferriss25:29

      Mm.

   9. PADr. Peter Attia25:29

      And, and so I knew that, but I think that piece of information was sort of, like, fleeting in the excitement when the box came.

   10. TFTim Ferriss25:35

       [laughs]

   11. PADr. Peter Attia25:35

       And so I tear open the box, and also there was a note in there that explained a somewhat palatable cocktail that you could, like, you know, mix th- like how you could mix this with 10 other things, and I just disregarded that, and I just took out, like, the 50-milliliter flask, and I chugged it. And I remember it was, like, 6:00 in the morning, 'cause my wife was still sleeping, and, you know, all these thoughts go through your mind. So first of all, you drink it, and it tasted like, like how I imagine jet fuel or diesel would taste.

   12. TFTim Ferriss26:07

       [laughs]

   13. PADr. Peter Attia26:07

       You know, if you've ever smelled distillate, it's this horrible odor, and you can sort of imagine what it would taste like. This is what it tasted like. And so my first thought was, "Goddamn, like, what if I go blind?"

   14. TFTim Ferriss26:17

       [laughs]

   15. PADr. Peter Attia26:17

       Like, "What if there's, like, methanol in here? Like, what did I just do?"

   16. TFTim Ferriss26:21

       [laughs]

   17. PADr. Peter Attia26:22

       And then my next thought was just, "Oh my God, you're gagging. I mean, you're really gagging, and now you're-

   18. TFTim Ferriss26:27

       [laughs]

   19. PADr. Peter Attia26:27

       ... if you puke this stuff up, you're gonna have to, like, lick up your puke and this stuff. I mean-

   20. TFTim Ferriss26:32

       [laughs]

   21. PADr. Peter Attia26:32

       ... it's just gonna be a disaster, right? [laughs] And so I'm, like, retching and gagging, and, like, trying not to wake up the family, and trying not to-

   22. TFTim Ferriss26:42

       [laughs]

   23. PADr. Peter Attia26:43

       ... like spew my ketone esters all over the kitchen.

   24. TFTim Ferriss26:46

       [laughs]

   25. PADr. Peter Attia26:46

       And it took, like, 20 minutes for me to get out and do my bike ride, which was the whole purpose of that experiment.

   26. TFTim Ferriss26:51

       Must have been a record-setter. [laughs]

   27. PADr. Peter Attia26:53

       Oh, God, it was, um... Those things are, those things are unbearable, so, you know, that, you know, until they figure out a way-

   28. TFTim Ferriss27:02

       And, uh, y-

   29. PADr. Peter Attia27:02

       Yeah

   30. TFTim Ferriss27:02

       ... no, just, just to put that in perspective, I, I ha- I'm speculating here, but correct me if I'm wrong, I would imagine, much like myself, you've, you've made a somewhat secondary career of choking down foul-tasting shit, like ge- you know, gels on rides or, like, all these protein powders. Like, the most hideous s- ostensibly, you know, performance-enhancing sports supplements. So you get to a point where you're like, "I've had bad stuff. How bad could it really be?" [laughs]
9. 30:53 – 35:07

   Ketosis vs. ketoacidosis: clearing up a common safety confusion

   1. TFTim Ferriss30:53

      Got it. Cool. And the, uh, now ketosis is a really fascinating state, and I, I don't, we don't have to delve too far into the, uh... Well, to, maybe just to address a, a common point of confusion, uh, people sometimes, uh, fear ketosis, thinking of it as ketoacidosis. Could you, uh, a- as observed in some people with diabetes.

   2. PADr. Peter Attia31:18

      Right.

   3. TFTim Ferriss31:18

      Um, they're not the same thing, as, as I understand it, or, you know, what is-

   4. PADr. Peter Attia31:22

      That, that's correct, yeah. They're, they're, they're related in the way that a house fire and a, and a fireplace are related.

   5. TFTim Ferriss31:30

      Hmm.

   6. PADr. Peter Attia31:30

      Um, so when a house is on fire, there's fire everywhere, and when you have a, a fireplace on, th- there's fire in there. Um, so, so they have a, they have a, they have an association, but that's where it ends, right? Whereas in the, the fireplace is, like, a well-controlled thing that actually adds some value, whether it be light or heat. The house fire is obviously not a controlled thing, and therefore it's not a positive thing. It's a destructive thing. So ketoacidosis is indeed a very destructive phenomenon, and it is a situation that rises almost exclusively in people with type 1 diabetes. Now, I've read some really interesting case reports of people who are not type 1 diabetic who have had ketoacidosis, but the, the, the examples of that are so rare that it's, I think it's just almost confusing to talk about them. So-

   7. TFTim Ferriss32:16

      Yeah

   8. PADr. Peter Attia32:16

      ... for, for the purpose of most people, a ketoacidosis is a state that occurs, um, usually when someone with type, type 1 diabetes gets sick. That's, that's usually, there's usually a precipitating event, and what basically happens is a deficiency of insulin, 'cause a type 1 diabetic requires exogenous insulin. They have to be injecting themselves with insulin. So you have, um, a mismatch between the need for insulin and glucose, and what's basically happening is in the absence of insulin, which actually suppresses ketones, their, their ketone levels rise. And, um, once the ketones get kind of north of 15, 1-5 millimolars, and certainly any higher, you know, 50, uh, 20 to 25 millimolars, you basically get into an acid-base problem where the pH now starts to drop, and so you, you get what's called a metabolic acidosis in response to that. And so, you know, I feel like I must have taken care of 100 people with, with ketoacidosis when I was in, back in the emergency room. It's a, it's, it's a life-threatening illness, but the good news, it's a very simple treatment. You give them massive amounts of IV fluid, glucose, insulin, potassium, and they're usually better within two days. Now, ketosis, totally different. Someone who has a normal working pancreas, um, can't really generate ketones north of... You know, I've heard of the odd person who can get up to 9 or 10 millimolars, but for most people, even if they starved themselves for two weeks, uh, and in, and certainly in Cahill's subjects over, gosh, I think as high as 40 days, um, in the longest Cahill cohort, you know, they s- they plateau at 6 millimolars.

   9. TFTim Ferriss33:52

      Mm-hmm.

   10. PADr. Peter Attia33:52

       Um, which is still a very high level, but it's nowhere near the level that produces acidosis.

   11. TFTim Ferriss33:57

       Yeah.

   12. PADr. Peter Attia33:57

       Um, and that's because there's an auto-regulatory feedback from insulin.

   13. TFTim Ferriss34:01

       Now, the-- So I, I plateaued personally at about 6, uh, millimolars when I was, uh-

   14. PADr. Peter Attia34:06

       Okay

   15. TFTim Ferriss34:06

       ... doing my, my seven-day fast. The, um, so just, just to add something to what you just said, so for those people listening, if you go on the internet and you're researching ketosis and you see someone say ketosis is very dangerous and they link to an article, make sure that they are referring to, uh, nutritional ketosis, not ketoacidosis. It's very commonly mixed up. The other just, uh, tip I wanted to offer people who may not be very familiar with scientific terminology is a good mnemonic for remembering the difference between exogenous and endogenous is thinking of an exoskeleton on an insect where their skeleton is on the outside. So, so exo typically means administered from the outside. You're not producing it in your own body, so endogenous versus exogenous. Uh, the, the-- I was hoping, Peter, that you could describe for people listening an experiment you did which highlights your wonderful ob, uh, obsession and the, the metabolic chambers, and I thought

10. 35:07 – 46:28

    Metabolic chambers and measuring energy expenditure: what they are and what Peter learned

    1. TFTim Ferriss35:07

       you, if, if you wouldn't mind just briefly describing, uh, sort of the standardized experimentation that you did in these metabolic chambers. Most people don't e- don't even know probably what these chambers are or what they're used for, but I'd love to hear you describe that if you wouldn't mind.

    2. PADr. Peter Attia35:23

       So, um, I guess going back to NuSI, one of the types of experiments that, uh, Gary and I felt were really essential to be funded were the types of experiments that examined what we think is perhaps one of the most important questions in all of obesity, right? Which is, is obesity simply a disorder where people consume too many calories, or does the type of calorie they consume, uh, play just as much a role, right? In, in other words, there's no dispute that someone who's gaining weight is eating more calories than they're expending, and we have the first law of thermodynamics to thank for that wonderful fact. Um, it's just not particularly interesting. It's sort of like saying, "Hey, Tim, um, do you know why Bill Gates is so rich? He's so rich 'cause he makes more money than he spends."

    3. TFTim Ferriss36:10

       [laughs]

    4. PADr. Peter Attia36:11

       Like-

    5. TFTim Ferriss36:12

       Right

    6. PADr. Peter Attia36:12

       ... thanks, right? I mean-

    7. TFTim Ferriss36:15

       Biography complete, right?

    8. PADr. Peter Attia36:16

       Right. [laughs] I'm Peter Graves.

    9. TFTim Ferriss36:18

       [laughs]

    10. PADr. Peter Attia36:19

        Thanks for watching Biography. Um, so, so yeah, so it really irks me when we talk about obesity through the lens of it's an eating disorder. People eat more than they expend. Like, yeah, no shit, Sherlock. What I really wanna know is why do they eat more than they expend, right?

    11. TFTim Ferriss36:33

        Right.

    12. PADr. Peter Attia36:34

        What is it that's driving that? And so one of the hypotheses is the types of calories we consume could actually be Uh, feeding back on the two systems that regulate what we eat and what we expend, being your appetite. In other words, are there some foods that make you want to eat more? And secondly, your what we call non-deliberate energy expenditure, meaning how much energy do you expend? So to your question about the chambers, the-

    13. TFTim Ferriss37:01

        Is that the same as resting metabolic rate?

    14. PADr. Peter Attia37:04

        Um, yeah, there's, there's a little bit of confusion between all of the restings and, and basal metabolic rates, but I, I think the easiest way to describe it, that's why I use the term non-deliberate energy expenditure. It's sort of like, okay, you can go out for a run and burn 5,000 cal- or sorry, 500 calories, and you can climb a flight of stairs and burn four calories, but what I really care about is, and what we know from studying people for forever, is the majority of the calories that the average person is burning is the calories they're burning when they're doing nothing.

    15. TFTim Ferriss37:32

        Got it.

    16. PADr. Peter Attia37:32

        It's when you're sleeping, when you're sitting down, when you're... And so we measure that in a way, and, um, we can also measure the total energy expenditure. So the question is, can a change in macronutrient composition alter your appetite and your energy expenditure? Now measuring appetite, we could talk about that. We could spend two hours just talking about how you measure appetite and appetitive behavior. We'll, we'll save that for another day. On the energy expenditure side, there's really two ways to measure energy expenditure. Um, there's-

    17. TFTim Ferriss38:01

        And just, sorry to interrupt, Peter, just for those people who may not be deep in the nutritional world, so macronutrients, and again, feel free to correct me, Peter, at any point, but we're, you're talking about this, this, the distinction between protein, carbohydrate, and fat principally. Is that right?

    18. PADr. Peter Attia38:16

        Correct. That's correct. And, and the reason, I, I'm gl- glad you brought that up, the reason we're asking that question is not because we think that that's the perfect division amongst nutrients, right? I mean, there's a million different ways to distinguish between, you know, a piece of broccoli and a piece of, uh, bread. Um, one of them might just be, you know, and even the macronutrient composition isn't the best one there. Um, but what we're really interested in is that we have a pretty good understanding of how macronutrients impact hormones and enzymes in the body.

    19. TFTim Ferriss38:45

        Right.

    20. PADr. Peter Attia38:45

        And how those enzymes may regulate fat cell accumulation, the accumulation of fat within fat cells, adipocytes. So this business of measuring energy expenditure is really tricky. Um, and the two ways to do it, I've participated in both of these. One is a measure using, um, doubly labeled water, and another one is a technique, uh, called indirect calorimetry. And, um, so anybody who's had a VO2 max test has actually done indirect calorimetry. So if they've been on that treadmill or on the rowing machine or whatever, they've got that mask on them, it's actually sampling the amount of oxygen that they're using and the amount of CO2 that they're generating. And m- some, some of your listeners may, may know that there's a ratio between those two. So the ratio of the CO2 that you expend, which is called VCO2, the ventilatory CO2, over the ratio of oxygen consumed is called RQ, respiratory quotient. And there's a mathematical relationship that ties all of those into the amount of energy you're consuming. So that's why when somebody does a treadmill test with one of those masks, we can tell two really exciting things about them. One is how much energy they use for that given task, and perhaps as interestingly, if not more interestingly, where they got that energy from. Did they break down glucose or did they use fat?

    21. TFTim Ferriss40:07

        Mm-hmm.

    22. PADr. Peter Attia40:08

        So what if you wanna do this for a long period of time and you don't wanna stick a mask on somebody? So then what you do is they build these rooms, these super-duper NASA airtight rooms with double-layered gas-sealed doors and windows and everything, and they s- the, the room has thousands of air sensors in it that sample frequently, generally about every 15 seconds, um, the concentration of CO2 and O2 in the room, and they then calculate on a minute-by-minute or second-by-second basis how much oxygen you're consuming as the subject in that room and how much CO2 you're producing. And you'll typically spend 24 hours to 48 hours at a time in these lockdown rooms. Of course, they're handing food to you through a doubly sealed door, so you're not ever, even during the transfer of food or bodily fluids, you're not, um, contaminating the air in the room. And there's an engineering core outside the room that's just getting all this data, and when, you know, when the day is done, you can tell exactly how many calories you burned that day and where you got that energy from. Did you burn, you know, fat stores or glucose stores?

    23. TFTim Ferriss41:18

        And, and, uh, again, correct me if I'm wrong, but you did this in, you repeated an experiment in a number of these chambers, and you standardized the experiment where you were consuming exactly the same meals, performing exactly the same exercise routines. Um, what, uh, what were some interesting results or unusual, uh, data that came out of those experiments?

    24. PADr. Peter Attia41:43

        Well, you know, first of all, the reason I wanted to do this was because, uh, one of the first studies that NUSI funded, um, was, was, uh, relying on these sorts of chambers across the country, and, um, so at four different sites actually. There aren't many of these things. I think there's only, like, you know, maybe 15, 16 of these chambers in the United States. I mean, they're, they're very expensive. It's a pretty costly piece of equipment. Um, so one is I wanted to know what, what we were basically asking subjects to go through, because in these experiments we were asking subjects to, you know, spend two days a week inside a chamber for several months. So I wanted to at least get a sense of what that would feel like. I mean, how does that drive you crazy? What's that like? The second thing I wanted to get a sense of was, as you s- alluded to, how reproducible are the results from one center to another, from one site to a site? Um, and then of course, there's just always the sort of morbid curiosity of what will we learn? Like what, you know, I, I'm curious as to how these things change. I don't, I don't, I have no idea how much energy I expend in a day, nor do I, I have an understanding of how much of that is basal versus activity related. And so, um, I did this across three, uh, three separate, you know, stints. And, um, as you were absolutely correct, so it was an exact finite, uh, meal. Now, I realized after the first day we did it, we underdid the meal. The i- in an ideal world, you match your intake to your expenditure. So a priori, we had designed what the experiment was going to look like to try to replicate my life outside of a chamber. So, you know, down to the minute, we knew everything that was gonna happen. So I was gonna go to sleep at this hour, I was gonna wake up at this hour, I was going to, you know, do this, I was gonna, you know, get on the bike, in the stationary bike, and ride at this many watts, 'cause it had a power meter. I was gonna do this many push-ups, this many plyometrics, this many sit-ups, eat the meal at this time, work on the computer for this time. Like, we had-- So we did it the exact same way each time, and after the first day, it was clear that the cal- we had only given me 3,000 calories, but my energy expenditure was about 4,300 or 4,400 kilocalories.

    25. TFTim Ferriss43:54

        [laughs]

    26. PADr. Peter Attia43:54

        So I had, I had a 1,400-calorie deficit, and of course, I wanted to fix that the next time, but I was like, "You know what? Let's-- I'd rather we just stay reproducible and, and do it." So, um, one of the things that I found interesting was, you know, how high my, my metabolic rate was at rest. So, um, to do this in a chamber, you basically spend two hours wide awake, doing nothing, laying down, and that produces a slightly higher metabolic rate than when you're sleeping. Um, but it's the closest thing we have to a true resting energy expenditure.

    27. TFTim Ferriss44:24

        Are you reading or are you just staring at the ceiling for two hours?

    28. PADr. Peter Attia44:27

        No, no. It's, it's literally-- It's-- If, if drinking those ketones was the worst thing I've ever done-

    29. TFTim Ferriss44:31

        [laughs]

    30. PADr. Peter Attia44:32

        ... uh, and then almost dying getting an insulin suppression test was the second worst thing I've ever done, the third worst thing I've ever done is having to spend those two-hour blocks doing nothing, 'cause you're not allowed to do anything.
11. 46:28 – 57:52

    Why single blood-test snapshots can mislead: inflammation, exercise, and standardization

    1. TFTim Ferriss46:28

       Right. And, you know, it raises a question. I'm su- you may have thought about this, you probably have thought about it before, but looking at, say, blood ranges, uh, the, the, with the in range, uh, well, I guess it would be the normal range for various, um, biomarkers when you have blood tests performed, whether that be hemoglobin A1C or, uh, total cholesterol or anything else, and how those numbers change over time. And what I've just become so fascinated by is looking at how difficult it is to find someone who is living hard, you know, living and playing hard, whether they're, uh, an athlete or just someone who's a type A personality CEO type, who isn't constantly out of range on at least a handful of things. And the, the questions that I've started to ask are, is it-- if, if we're not able to get the nutrition we need ostensibly as reflected in these tests, how the hell ha- did our, you know, ancient predecessors ever pull it off, number one? Uh, a- and does that in fact mean that they didn't and it's, it's the, it's the, a flaw in the test? Uh, or is, is there, rather than not getting enough of something, is modern man, uh, exposed to various types of, whether it's contaminants or estrogenic compounds in shampoo or whoever, who the hell knows, that create those deficiencies? It's not that we're not getting enough, it's that there are things that are, that are causing deficiencies. Or, again, just the tests are influenced by lobbying and all these other things, and they're just, they're not reliable. I mean, how, how do you think-- how do you even start to think about that stuff? Because I have-- Thankfully, there are doctors I work with who can look at the tests and say, you know, like, "This is slightly out of range. I wouldn't worry about it at all for these following reasons." Uh, but for people who go to a doctor once a year, get an annual checkup, and get prescribed drugs for anything that's out of range, just based on that one snapshot, I mean, how do you even start to think about this stuff? I know it's a long question, but it's, it's something that's been bothering me recently.

    2. PADr. Peter Attia48:40

       Yeah, it's, uh, it's something I think a lot about. I became most interested in this a couple of years ago when, um... Well, you know, to back up for a second, I, I do, uh, you know, I have, like, my own centrifugation blood draw kit at home and stuff like that because I'm doing blood work a lot on myself and on anyone who, uh, is unlucky enough to walk in the front door.

    3. TFTim Ferriss48:59

       [laughs]

    4. PADr. Peter Attia49:01

       O- o- one of the things I noticed was just the huge variability in my lipoproteins. These are the, um, um, p- molecules that carry around cholesterol and triglycerides in our body. And, you know, conventional thinking would be, hey, if you're not taking any drugs and/or your diet's not really changing much, why would those things vary? And yet, um, I noticed, um, I had a dental abscess that was, I was sort of ignoring 'cause I was too busy, and it was sort of getting pretty bad, and I eventually just had to get the tooth yanked out, and I noticed that the changes in my lipoproteins were enormous. And so I started realizing, hey, obviously inflammation, absent any other change, is changing these things. And then I got this idea, which was, I wonder how much exercise is impacting it, right?

    5. TFTim Ferriss49:48

       Hmm.

    6. PADr. Peter Attia49:49

       So I, um, did an, did an experiment with the help of actually the lab that does all the assay, 'cause it w- this was such an exhaustive thing, I, I, I couldn't do it on my own. So basically, I did, um, nine super comprehensive, like 10-tube blood draws on myself in three days, um, but sandwiched around similar activity. So I would do an immediate morning fasting one, then I would do an immediate hard workout, then immediately do one after, and then immediately do one three hours later. And there are some things that you should expect to vary a lot due to that kind of variation. You should expect your glucose levels to change, probably your triglycerides, probably your insulin levels, right? There are other things that you'd think, wow, if they change and we're prescribing medication to people based on those, such as CRP, LDL cholesterol, LDL particle number, these sorts of things, um, we maybe need to ask ourselves a question, right? And so sure enough, the changes were amazing, right? I mean, I couldn't believe what a hard workout would do, how much crappier it made you look, um-

    7. TFTim Ferriss50:57

       Hmm

    8. PADr. Peter Attia50:57

       ... on paper. Um, the first time I ever did this, actually, Tim, was aft- was in 2005 when I swam from, uh, uh, Catalina Island to LA. And I had my friend, uh, Mark Lewis, who's an anesthesiologist, draw my blood like 10 minutes before I got in the water on Catalina Island, and then 10 minutes after I got out of the water in LA, you know, 10 and a half hours later. And, um, it was a real epiphany for me because I had developed something called systemic inflammatory response syndrome, SIRS, which is something that we typically see in hospitalized patients who have horrible infections or who have, who have been in real bad trauma, you know, gunshot tra- you know, car accident, that sort of thing. So, you know, my platelets went from a normal level to six times normal. My white blood cell count went from, um, you know, normal to sort of, mm, I don't know, five times normal. Um, you know, all of these huge changes occurred in my blood that looked like you, you wouldn't distinguish me from someone who had just been shot. And in many ways, you could argue, look, that's sort of what swimming for 10 and a half hours is, right? And maybe, maybe the changes we're seeing are due to these things. So, you know, I g- I guess I would say this. I've always been hesitant to treat a patient for any snapshot, right? No matter how bad it looks, right?

    9. TFTim Ferriss52:21

       Yep.

    10. PADr. Peter Attia52:22

        Because I don't know... You know, for example, I saw a guy recently who, I, on his morning cortisol level, it was like five times the normal level. So you might think, wow, this guy's got an adrenal tumor, right?

    11. TFTim Ferriss52:36

        Right.

    12. PADr. Peter Attia52:36

        But a little follow-up question realized that at 3:00 that morning, the night he, you know, a few hours before this blood draw, the water heater blew up in his house. So the normal level of morning cortisol assumes a guy sleeps through the night, not that he has to like [laughs]

    13. TFTim Ferriss52:51

        Had to deal with a household emergency

    14. PADr. Peter Attia52:52

        ... de-flood his house. Exactly, right?

    15. TFTim Ferriss52:53

        [laughs]

    16. PADr. Peter Attia52:53

        So a- again, a silly example, but I do think the, the, the sort of big picture matters a little bit more than the immediate value sitting in front of you. Now, to your first question, Tim, I don't know that the values we deem normal have any bearing on what our ancestors would have looked like. I mean, uh, and I think this is a knowable question. I just, I don't think I know the, I kn- I, I don't know the answer. I, I do believe that there's somebody out there that could tell you, 'cause there's a handful of Aboriginal populations, um, that, that, that I think still exist, you know, in Australia, for example, where we can get a pretty good idea of what our ancestors probably looked like, and, and I would be interested to know how far outside of, quote-unquote, "norm" are they.

    17. TFTim Ferriss53:38

        Uh, definitely, and it, it's not to say that, uh, you know, perhaps the, the, the paleo ideal is not the target we should shoot for, but it makes me wonder, like if you're in Iceland and, uh, you're getting four hours of daylight for three to four months, do you really have the same vitamin D level as someone [laughs] who's like equatorial? Like probab- I don't know, but probably not, I would guess. Uh, and does it really matter if that's your ethnic background? And, uh, you know, the, the identification of, uh, s- uh, uncontaminated indigenous populations has been, been of interest to me recently because of the Lyme disease and the long-term antibiotic use and trying to research, uh, fecal matter transplants, shit swaps as they're scientifically known, and, uh, look, tr- realizing how hard it is to find a population that has not been, uh, chronically administered antibiotics, whether in childhood or in adulthood. And, uh, Tanzania, apparently, there are a handful of places where researchers are flocking, and there aren't that many. Uh, it's, it really-

    18. PADr. Peter Attia54:48

        That's really interesting.

    19. TFTim Ferriss54:49

        Yeah. It's really-

    20. PADr. Peter Attia54:50

        I had not thought of that.

    21. TFTim Ferriss54:51

        It's fascinating, and I was actually going to do a fecal matter transplant. As a side note, uh, you can do the, uh, you know, reverse enema, but there, there, there are people now who are also, uh ... creating capsules that are frozen. Uh, I think they're typically frozen and then swallowed. Uh, the reason I decided against doing an FMT, as they call them, is that there are many, um... I spoke with a gastroenterol- entrologist who felt like the, the, if you were to create a spreadsheet of our, our known risks and the, the known potential benefits, you might decide to do a fecal matter transplant. But how many pathogens, how many different types of communicable diseases have we not identified that might be transmitted in a fecal matter transplant? And their hypothesis was probably a lot. I mean, we think we figured out things like hepatitis, but God knows what else is in there. So if you don't have to do it, if you're not, you know, dying of Crohn's disease or who knows, then, uh, if it's a, it's a, if it's a total optional thing, kind of like you and your, uh, bariatric band, then probably not a good idea to do a fecal matter transplant. But I, the, this, this, um, leads me just as it relates to the blood testing... Oh, just as a side note, a- and I'm not a doctor, I don't play one on the internet, but, uh, maybe Peter, you could share your thoughts on, on this. And just as a cautionary note, I have so many friends here, uh, in the US and elsewhere who are, again, they, they have one or two checkups a year. If anything's out of range, they're prescribed medication. And they, uh, the doctor will do their best, and they're constrained by a lot of things, but they'll do their best to trend, and they'll look at previous blood tests. And what astonishes me is that the day of the week and the time of the day of the draw is not standardized. So for instance, I have friends, uh, you know, male friends who are, who are now on, uh, prescription testosterone. They've been given supplemental testosterone because their testosterone was 200 points lower than a previous test. And, uh, if I look at their blood tests, not as a doctor, just as a friend, obviously, out of curiosity, I'm like, "Well, wait a second. Like, you had one test at 8:00 in the morning and another one at 11:30." And when I've done my own, uh, I've done so many different blood tests, it's, there's a very clear peak that then drops off really quickly for me, depending on the time of the day. And certainly, like your friend with his, uh, water heater disaster, if you do a test on, say, a Thursday after three or four days of no drinking, and then a test on Monday morning after a weekend of binge drinking, y- your values are inevitably going to be kind of all over the place. So just the, the importance of standardizing time, I think is, uh, for any type of trending, really important for people to keep in mind. But just-

    22. PADr. Peter Attia57:51

        Completely agree.

12. 57:52 – 1:14:16

    The longevity “manifesto”: balancing lifespan vs performance, and the role of IGF-1 and diet composition

    1. TFTim Ferriss57:52

       Yeah. Uh, so, so Peter, you, you sent me something very interesting a couple of days ago, and, [laughs] uh, the, uh, the email that turned into a manifesto. Uh, you sent me, uh, a, you know, 20-some page document that I, I do think you should turn into something, uh, about your thinking on basically hacking lifespan and performance and, and how to choose the appropriate, the appropriate blend of the two for yourself. And, uh, I was, I was hoping maybe you could, uh, comment on perhaps the, the common misconceptions or just sloppy thinking around life extension, if, uh, if, if we could start there.

    2. PADr. Peter Attia58:42

       Yeah. So I, I, I don't know wh- why it occurs, but I guess once we hit our 40s, where, where I'm comfortably now, um, and maybe it's having kids, I don't know, but something sort of changes where we become a little bit more interested in longevity than we do performance, right? You know, I think my days of, uh, sort of trying to be the best at anything are long behind me. Um, I do still compete in at least one sport competitively. I do sort of, at least with myself, give a damn about how I do. But the reality of it is nobody actually cares, right? Like, I don't, it's not like, you know, it's not like Pinarello is sponsoring me, and if I don't have a good race this weekend, they're gonna drop me. Like, nobody cares.

    3. TFTim Ferriss59:21

       [laughs]

    4. PADr. Peter Attia59:21

       My wife, I, I don't think my wife could tell you within, like, 200%, like, my times, right? Like, it's just-

    5. TFTim Ferriss59:29

       This is for the, this is for the 20-kilometer time trial.

    6. PADr. Peter Attia59:31

       Yeah, yeah. Exactly. Like, I mean, it's just like, who cares, right?

    7. TFTim Ferriss59:34

       [laughs]

    8. PADr. Peter Attia59:34

       Nobody cares except me.

    9. TFTim Ferriss59:36

       [laughs]

    10. PADr. Peter Attia59:36

        So, so, but this was all catalyzed, as you said, through an email that a friend sent me over the summer. So it's a good friend of mine who's probably 50 years old. Um, you know, super-duper stud in all manners of life. Um, very, very successful guy. Does, you know, Ironman, half Ironman all the time, and I think he had just done sort of like his 20th half Ironman or something like that. And he said, um, "You know, Peter, I feel like I'm 50 now. I don't know that I need to do these anymore. I really wanna start thinking about how I should shift my exercise towards increasing my longevity as opposed to fixating on performance of an athletic event." And so I responded to that email with a very long email, and that email, thanks to Evernote, turned into basically a collection of all of my thoughts on this, and that's actually what I sent you the other day because I, I knew if anybody would like it, you would get a kick out of it. Um-

    11. TFTim Ferriss1:00:35

        Yeah. Loved it.

    12. PADr. Peter Attia1:00:36

        Yeah. So, so it's, it's really been an obsession of mine for a long period of time. I think it's just crystallized into something that's getting more deliberate focus, right? Which is, how do you balance the desire to live longer, to live more years on this earth, with the desire to enjoy them and perform well, right? 'Cause you can come up with all of these sort of thought experiments that are idiotic, and I include one in this piece, right? Which is, if someone said to me, "Peter, you can live to be 150 years old in perfect health- But you have to sit in a dark room alone and never see your family again. Would you do it? I mean, not a chance, right?

    13. TFTim Ferriss1:01:20

        Right.

    14. PADr. Peter Attia1:01:20

        Like, I'd rather die in five years than have to do that.

    15. TFTim Ferriss1:01:25

        So it's not-

    16. PADr. Peter Attia1:01:25

        There's also been some evidence in nematodes, I'm not sure in mice models or anything, that show that, uh, that avoiding ejaculation can extend your lifespan. Similar idea.

    17. TFTim Ferriss1:01:34

        [laughs]

    18. PADr. Peter Attia1:01:35

        Well, we know castration can.

    19. TFTim Ferriss1:01:37

        Oh, fantastic. [laughs]

    20. PADr. Peter Attia1:01:38

        So yeah, castration has been shown-

    21. TFTim Ferriss1:01:39

        That's interesting

    22. PADr. Peter Attia1:01:40

        ... in most animal models to increase longevity.

    23. TFTim Ferriss1:01:42

        Nice.

    24. PADr. Peter Attia1:01:42

        But again-

    25. TFTim Ferriss1:01:43

        Solves the volitional ejaculation issue. [laughs]

    26. PADr. Peter Attia1:01:45

        Yeah, yeah. So, um, so, so there has to be a balance, right? Uh, similarly, you know, I think there's pretty good evidence that there are certain dietary strategies that could really increase longevity, but if they come at a cost that, uh, detracts from wanting to live, you know, they might not be worth it. So that, that's one macro theme. The other macro theme is we do need to distinguish between, uh, 'cause these are sometimes orthogonal, what I would call cellular health and what I would call organism health. So I think there are things that matter on a cellular level. There are things that can delay aging of the cells within our body, um, and those aren't necessarily things that produce the best output of the organism. And so I suspect that the solutions to this thing, which I, you know, I have lots of thoughts on, um, are not going to be simple. Um, there's gonna be a few 80/20 pieces thrown in, and a little bit of bootstrapping, and, uh, a little bit of empirical feedback, right? 'Cause I d- I think there's gonna be some people that respond more favorably to some things versus others.

    27. TFTim Ferriss1:02:51

        Yeah.

    28. PADr. Peter Attia1:02:51

        Uh, and I do think there's some really exciting pharmacologic plays that are out there, um, that, you know, need further study, but I think could sort of move the needle.

    29. TFTim Ferriss1:02:59

        Now, so just conceptually, I, I think people will find a, a couple, a, a number of things interesting that I'll just highlight here. You know, the, one is the thinking of life extension or death avoidance, right? So I think death avoidance is sort of a, uh, an interesting phrasing. Uh, but then also having a framework, like you said, two issues, you know, one's defensive and the other's on offensive. But, uh, delaying dying and optimizing living, right? Uh, and put another way, getting sort of 80% of the long-term benefit while still getting, let's just argue 50 to 60% of the short-term pleasure. I, I just think it's written in a very compelling way. I had a couple of very, very specific questions for you. Uh, the, the first was, um, [laughs] people might find this amusing, so I'll just say I, I, I, I edited, I added a word to a line here. Uh, you, you have a line that is, "Streamlining this a bit further, once you've arrived into your 40s or 50s and assuming you're not a smoker or heavy drinker, you don't do IV drugs or engage in su-" blah, da, da, da. And I put, you should put, "you don't do bad IV drugs," in parentheses. [laughs]

    30. PADr. Peter Attia1:04:12

        [laughs]
13. 1:14:16 – 1:31:13

    Endurance exercise downside: atrial fibrillation risk, right-heart stretch, and rethinking training priorities

    1. TFTim Ferriss1:14:16

       So speaking of context specific and, uh, s- and different activities or it could be interventions, whatever you wanna call them, not always being 100% good, or very seldom being 100% good, 100% bad, uh, I w- I wanted to chat about something that, that, uh, came up in this manifesto, and that is that, uh, there appears to be evidence that heavy amounts of aerobic, especially sub-threshold efforts, activity may result in right-sided cardiac di- dilatation it looks like, stretching, uh, and which may be the driver of paradoxical ri- rise we're seeing in dysrhythmia. Um, so perhaps you could, you could, uh, just explain that for, uh, s- the lay audience that's listening to this, but the idea that what we think is exactly what we should be doing, uh, or that some people might think could be doing us, in fact, harm. And the question I put in the margins there was, sub-threshold, what percentage max heart rate, rate are we talking about? Because later in the piece, uh, y- there's a discussion of walking, um, which, which gets the green light. Uh, but, uh, I'd love to hear you expand on this a little bit.

    2. PADr. Peter Attia1:15:33

       Yeah, so it's been generally sort of not acknowledged that readily, but if you actually go back and look through the literature, which I did about three months ago, I wanted to look at the literature of atrial fibrillation, which I'll explain in a second, in athletes. So why did I wanna do this? Because I basically started noticing every person I knew was getting AFib. So people who were older than me, my peers, people, you know, patients that were coming to me who were s- you know, stud athletes. I mean, obviously they weren't all getting atrial fibrillation, but enough of them were that I was sort of like, "What in the heck is going on here?" So atrial fibrillation is a rhythm of the heart where the atrium, that's the smaller, um, collection chambers on the top of the heart, to be contrasted with the ventricles that have to do the big pumping. Um, the atria, which only transmit blood into the ventricles, if, if, if, if you get beats that are generated there that are not what we would call a normal sinus beat, so there's a part of the heart that generates, like there's a pacemaker within the heart that generates the normal, regular beat that you can feel if you put your hand on your wrist or your chest, an atrial fibrillation is an irregularly irregular beat. And it often gets kicked off with what's, what we call a rapid ventricular response. So it, it can sometimes start beating so quickly that even the ventricle picks up that beat, and all of a sudden you've got this horrible heart rate. Atrial fibrillation is a very dangerous beat in the wrong patient. So it's very dangerous in people who are older or who get it for the reasons of, um, you know, ischemia, meaning, uh, l- lack of blood flow to the heart, because, uh, not only does it lead to demise directly, but it can predispose you to forming clots within the chambers of the heart that then, uh, get lodged up in the brain. So older patients who are on atrial fibrillation, even younger patients who are on it, where they stay in atrial fibrillation long enough, are usually put on bl- very aggressive blood thinning medication. So the question is why are all these athletes getting it, right? 'Cause it seems disproportionate, right? So if you look at the population as a whole and say, how many 40-year-olds have AFib? The answer is, like, none.

    3. TFTim Ferriss1:17:47

       Right.

    4. PADr. Peter Attia1:17:47

       But if you look at cyclists, it's like 10%, right?

    5. TFTim Ferriss1:17:51

       Mm.

    6. PADr. Peter Attia1:17:51

       If you look at runners, it's a little bit lower. Um, and, and so there's actually... So anyway, this is what I... So, so I basically started looking through all this literature, and, um, a couple things come up. So there's a guy by the name of James O'Keefe, who's a cardiologist at the university, I think he's at Wisconsin. Um, and he's, you know, a great athlete himself and a, and a cardiologist, but he's also been interested in this for a long period of time. Um, he, he's got some ideas which show, which suggest that long amounts of sort of pretty exhausting cardiac stuff, the stuff you'd experience if you were, you know, you know, riding, uh, in a, in an Iron Man or doing something really hard or running a marathon really hard, it actually creates a stretch in the heart. Now we know that's true. That's how we increase cardiac output. Um, but it does so at a level that the right side of the heart can't compensate as well as the left. So the left side of the heart is very muscular because it's needed to pump blood against the entire resistance of the body. The right side of the heart is actually not muscular because it only needs to pump against the lungs, which are a very low resistance system. So-

    7. TFTim Ferriss1:18:59

       Which si- which, which side has the, the higher musculature?

    8. PADr. Peter Attia1:19:03

       Left.

    9. TFTim Ferriss1:19:03

       Left.

    10. PADr. Peter Attia1:19:03

        So the left ventricle, if you, if you took a normal heart out of the body and did an autopsy on somebody or sampled, you know, took a heart out of a sheep's body or something, um, you'd see this very thick, muscular left wall, and then the right one collapses. You barely see it.

    11. TFTim Ferriss1:19:17

        Got it.

    12. PADr. Peter Attia1:19:18

        And again, it's because in normal physiology, one of them is pumping against, like, 120 millimeters of mercury, the other one's pumping against, like, 20 millimeters of mercury.

    13. TFTim Ferriss1:19:26

        Right. When you

    14. PADr. Peter Attia1:19:28

        Exercise. When you really, really throw down the hammer, you have to increase cardiac output, meaning how do we measure that? We measure that in liters per minute. How many liters per minute of blood are going through your body? And so if, if I'm sitting here right now talking with you, Tim, uh, you know, my cardiac output is three, four, maybe five liters per minute. When I'm in a race, um, you know, when I'm doing what we, an all-out threshold, sub-threshold effort, I'm at 25 to 30 liters per minute. And I get that not just by beating faster, which gets me part of it, but by taking bigger beats each time.

    15. TFTim Ferriss1:20:06

        S- stroke volume.

    16. PADr. Peter Attia1:20:06

        And that's the stretch. You got it. That's the stroke volume. And so what O'Keefe has argued and certainly showed in animal models, and there's a ton of epidemiology that certainly suggests it, um, although, you know, we just don't have a cl- I don't think we're ever gonna have a clinical trial that can demonstrate this one way or the other, is there's a subset of people, for reasons I don't know, who are susceptible, where chronic right-sided dilatation over and over again leads to distortion of the right side, which leads to atrial fibrillation, or worse, fatal dysrhythmias. You know, we do see it. Uh, fortunately it's quite rare, but nevertheless it's tragic, where we see these athletes dying suddenly. And this is not the, what we typically think of as the sudden athlete death, which is the, um, is, is actually massive left-sided hypertrophy. That's a separate cause. Um, but I think we're seeing more commonly, um, young athletes dropping dead from what looks like a heart attack, only to find out their coronary arteries are pristine.

    17. TFTim Ferriss1:21:02

        Huh. Now is, what should someone, if someone is not a professional athlete, like you said, they're not gonna lose a million dollar sponsorship deal by changing their form of exercise, w- tentatively, what would be your recommendations for perhaps things to minimize or, or ration a bit, or things to do more of?

    18. PADr. Peter Attia1:21:24

        Well, look, this is, this is where I'm certainly the most hypocritical in all of the things I think about, right? I mean, I-

    19. TFTim Ferriss1:21:30

        [laughs] You-

    20. PADr. Peter Attia1:21:31

        You know

    21. TFTim Ferriss1:21:31

        ... you're doing precisely.

    22. PADr. Peter Attia1:21:32

        Yeah, exactly. I mean, like, I, you know, a- and I, and I wrote about this. I'm very transparent about this, right? Which is right now I look at my approach to cycling as, um, completely illogical. Like, there's no upside in it, and there's just downside. And that says nothing about the risk of getting hit by a car and all the other stupid things that unfortunately happen. Um, but for whatever reason, it's scratching an itch within me that is giving me so much pleasure, that I'm just, uh, every year I just sort of say, "Well, one more year, one more year."

    23. TFTim Ferriss1:22:06

        [laughs]

    24. PADr. Peter Attia1:22:07

        And, and I don't know, maybe I'm waiting for that first bout of AFib and then I'm gonna be like, "I'm done," and hopefully the AFib goes away. So I think what I'd wanna reiterate is, look, it, you gotta balance your own happiness and sanity with sort of your desire to live as long as is humanly possible.

    25. TFTim Ferriss1:22:23

        Yeah.

    26. PADr. Peter Attia1:22:23

        And I think that if I couldn't ride my bike, I would just be very unhappy, no matter how much, even if it gave me an extra five years of life.

    27. TFTim Ferriss1:22:30

        Yeah.

    28. PADr. Peter Attia1:22:30

        Um, at some point that might not be true. That said, I, so, so, so for people that I take care of who are like me, I don't, I don't try to talk someone out of doing this, right? What I do though, Tim, is I, nothing breaks my heart more than seeing that person who's struggling to lose weight, who thinks that they need to be running, you know, 20 miles a week. And it's like they have no desire to do it, right? Their knees hurt, they hate it, and they're not losing weight. And I'm like, "Well, I've got great news for you. You don't ever need to run another step a day in your life."

    29. TFTim Ferriss1:23:00

        Mm-hmm.

    30. PADr. Peter Attia1:23:00

        Because there's no value in that, right? There is value in exercise, though, and I do think that the most important type of exercise, if you, especially in terms of bang for your buck, is going to be really high intensity, heavy strength training. Um, and it- it's a-
14. 1:31:13 – 2:03:34

    Rapid-fire closing: books, meditation approaches, definitions of success, and the fatty liver study pitch

    1. TFTim Ferriss1:31:13

       Mm-hmm. So a couple of, uh, I wanna ask you a couple of rapid-fire questions, then I know you have to get running. And, uh, if, if people would like to perhaps sometime here around too, definitely l- let us know, guys. Uh, I'm on Twitter, @TFerriss, T-F-E-R-I-S-S. What's your, what's your Twitter handle, uh, handle, Peter, if you have one?

    2. PADr. Peter Attia1:31:31

       Yeah, @PeterAttiaMD.

    3. TFTim Ferriss1:31:33

       That's easy. Uh, and I'll put all this in the show notes, guys. But the, the rapid-fire questions. So the first one I wanted to ask is, uh- Do you meditate, and if so, what type of meditation do you prefer?

    4. PADr. Peter Attia1:31:45

       Oh, sorry, can I not give you a rapid fire answer? [laughs]

    5. TFTim Ferriss1:31:50

       [laughs] Let me, let me start again. Let me d- let me, uh, switch the order. Yes, I'll, I've planted the seed on that one. [laughs]

    6. PADr. Peter Attia1:31:56

       [laughs]

    7. TFTim Ferriss1:31:56

       The, the, the first one is th- what book have you gifted to other people the most?

    8. PADr. Peter Attia1:32:03

       Um, probably Mistakes Were Made, But Not by Me.

    9. TFTim Ferriss1:32:07

       What is that book about?

    10. PADr. Peter Attia1:32:09

        Uh, actually, and the other one is Surely You're Joking, Mr. Feynman.

    11. TFTim Ferriss1:32:12

        Oh, great book.

    12. PADr. Peter Attia1:32:12

        Those would be a toss-up. Yeah.

    13. TFTim Ferriss1:32:13

        Great book.

    14. PADr. Peter Attia1:32:14

        Uh, so you know Surely You're Joking.

    15. TFTim Ferriss1:32:16

        Yep.

    16. PADr. Peter Attia1:32:16

        Uh, my son, by the way, which who he was born three months ago, his middle name is Feynman.

    17. TFTim Ferriss1:32:22

        Love it.

    18. PADr. Peter Attia1:32:22

        Um, which is, uh, so he's got big boots to fill.

    19. TFTim Ferriss1:32:25

        [laughs]

    20. PADr. Peter Attia1:32:25

        Um, um, so Surely You're Joking, Mr. Feynman is a ro- uh, sorry, Surely You're, uh, you know that book. Uh, Mistakes Were Made, But Not by Me is a, is a book about cognitive dissonance.

    21. TFTim Ferriss1:32:34

        Mm.

    22. PADr. Peter Attia1:32:35

        And y- you know, it's one of the few books that at the, at the moment I finished it, I not only reread it, but I, um, bought it for about 10 people. And, um, I think that the authors, uh, one of whom I've become very close friends with, and she is now actually an advisor to Nusi as well, her name is Carol Tavris. Um, one of the things the authors do such a great job of is really getting at the psychology of why it is that we are simply not wired to, uh, acknowledge mistakes when we make them, um, look for, you know, weaknesses in our, you know, in our thinking. And I just think that, you know, h- how do I make sure I go through life without becoming too, too sure of myself? Because, you know, on some levels, I am sure of myself, but at other levels, I have to realize, like, what, what can I do to make sure I'm not missing something that, um, that could allow me to do a better job, right?

    23. TFTim Ferriss1:33:30

        Right.

    24. PADr. Peter Attia1:33:30

        And, and so anyway, the, I think it's a fantastic book.

    25. TFTim Ferriss1:33:33

        Very cool. And, uh, that author's name is Carol Tavris, T-A-V-R-I-S, and, um-

    26. PADr. Peter Attia1:33:38

        Correct

    27. TFTim Ferriss1:33:39

        ... the other author is Elliot Aronson, for people interested. I'll put this in the show notes as well. Okay. So meditation. You don't have to give a rapid fire response. Uh, that's why it's called Rapid Fire Questions. You could take a half hour to answer. [laughs]

    28. PADr. Peter Attia1:33:52

        [laughs] Um, so, so when I think about the pillars of longevity, what are the things, what are the things that you've got at, what are the levers you have to pull to live the longest, most productive, high-performing life imaginable? It involves fixing your nutrition. We've talked about that. Changing your exercise. We've talked about that. Fixing your sleep. We have not talked about that, but that's important.

    29. TFTim Ferriss1:34:14

        Mm-hmm.

    30. PADr. Peter Attia1:34:15

        Um, using the right supplements. We've not talked about that. Modulating hormones as necessary. We've not really talked about that. Fixing anything that needs to be fixed on top of that pharmacologically, and I'm a huge proponent of pharmacotherapy under the right setting. The final component is managing your stress. So as a, as a guy who's thinking about this, I became really interested after actually reading Dan Harris's book. Um, which the title is blanking on me, but it's, like, 10% Happier, actually is the title-

Episode duration: 2:03:34