The Peter Attia Drive - #369 ‒ Rethinking protein needs for performance, muscle preservation, and longevity, and the mental and physical benefits of creatine supplementation and sauna use

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

00:00:16.540 my website, and my weekly newsletter all focus on the goal of translating the science of longevity

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00:00:53.200 of the subscription. If you want to learn more about the benefits of our premium membership,

00:00:58.020 head over to peteratiyahmd.com forward slash subscribe. My guest this week is Rhonda Patrick.

00:01:06.640 Rhonda, returning for her third conversation on the Drive, is a scientist, health educator,

00:01:11.620 and host of Found My Fitness podcast. Her work focuses on the intersection of nutrition,

00:01:17.520 aging, and disease prevention, and she is widely recognized for bringing clarity to complex topics

00:01:23.240 in health science. This is part two of a deep dive on protein, but we expand into other topics like

00:01:30.080 creatine supplementation and sauna use. In this episode, we discuss why the RDA for protein is too

00:01:35.980 low and why a new minimum, at least 50% more than the RDA, is needed to avoid negative protein balance.

00:01:43.300 The distinction between minimum, optimal, and high protein intake, and how activity level and aging

00:01:49.280 can affect requirements. Anabolic resistance, what it is, why inactivity drives it, and how resistance

00:01:55.840 training restores sensitivity. The role of protein in preventing frailty and sarcopenia,

00:02:02.000 and the quality of life implications in aging. Evidence on protein intake during pregnancy,

00:02:07.300 adolescence, weight loss, and while using GLP-1 agonists. Addressing the concerns about mTOR,

00:02:15.180 cancer risk, and reconciling protein intake with longevity research. The case for creatine,

00:02:21.900 how it enhances strength and endurance performance, its overlooked benefits for cognition and brain health,

00:02:27.820 and why dosing above 5 grams per day may be necessary. Practical guidelines on dosing,

00:02:34.420 formulation, and the populations who may benefit most. For example, vegetarians, older adults,

00:02:41.220 young athletes, older athletes. The science of sauna use, revisiting the mechanisms, especially as

00:02:48.200 they pertain to cardiovascular adaptations and heat shock proteins, dementia risk and cardiovascular

00:02:53.180 disease reduction, and best practices for temperature, duration, and frequency. How to weigh infrared

00:03:00.240 versus traditional dry saunas, and why going hotter isn't always better. I really enjoyed this

00:03:06.900 discussion with Rhonda, and I'm truly hopeful that this is the last time I need to do a podcast in a

00:03:12.480 very long time that addresses some of the controversy surrounding protein intake. So without further delay,

00:03:20.240 please enjoy my conversation with Rhonda Patrick.

00:03:28.500 Rhonda, so great to see you. And I didn't realize until a few minutes ago that the last time we spoke,

00:03:32.960 it was virtual. Yeah, good to see you. We go back a long way. You're still in our same former

00:03:38.760 neighborhood in San Diego. I know. And I'm thinking that you found the same feeling here in Austin.

00:03:44.260 Yeah, we did. All right. Well, there's a lot we want to chat about today. And I'm a little hesitant

00:03:50.140 to say this, but I do feel like reluctantly, we need to have one more discussion about a particular

00:03:56.800 macronutrient that seems to get a lot of attention lately. And I don't necessarily want to talk about

00:04:02.080 this because I think it's especially interesting, or even to which there's some new study that we need

00:04:06.940 to shed light on. But it does seem to remain somewhat surrounded in some controversy, which I

00:04:14.840 will refrain from publicly speculating on why said controversy exists. Although privately, I'm very

00:04:20.180 happy to speculate on all the reasons for it. So with that said, let's talk about protein.

00:04:25.880 Let's do it. I do think it's an important topic. You and I have probably talked to all the world's

00:04:31.820 experts on protein. And we were chatting a moment ago about this recommended daily allowance for

00:04:41.580 protein, the so-called RDA. And really what it should be called is the minimal daily allowance.

00:04:49.760 Recommended almost sounds like optimal in a way. Like I think people confuse that with the optimal

00:04:54.480 amount of protein, right? So it's kind of tricky. And I think that's an important place to start because

00:05:00.200 of that reason where this amount, which is 0.8 grams per kilogram body weight per day,

00:05:07.720 is the RDA for protein. And I know that you've probably had countless experts on talking about

00:05:14.640 this. I've had experts on talking about this, Stu Phillips being one. There's so many different

00:05:19.600 publications that, I mean, people can start off by reading one of them here by Stu Phillips.

00:05:24.160 Perspective, protein requirements and optimal intakes in aging. Are we ready to recommend more

00:05:29.120 than the recommended daily allowance? And there's several of these out there. This is just one.

00:05:35.100 And essentially, if you have the time and the willingness to go into the scientific literature

00:05:40.160 and actually read something for yourself or listen to The Drive or listen to my podcast and the actual

00:05:45.080 experts talking about it, what you will hear or what you will learn is that a lot of the studies that

00:05:51.100 were done to determine this RDA were flawed. They were called nitrogen balance studies. And for many

00:05:58.740 reasons, they're flawed. I don't want to get into all the technical reasons, but for one, what they

00:06:03.000 are doing is measuring the amount of nitrogen that is excreted in urine after you are metabolizing

00:06:09.120 protein. And some of the flaws that are, I would say, the most important here are that different types

00:06:15.120 of foods that have protein in them have different nitrogen to protein ratios. They're collecting

00:06:21.680 urine in which the case is that it's an incomplete collection. I mean, like when you pee in one of

00:06:25.940 those cups, you don't get all the urine. It's incomplete collection.

00:06:29.520 And we lose nitrogen through other means that is not just urine.

00:06:32.580 Yes, exactly. We lose nitrogen through other means. And so essentially, the signal to noise ratio is

00:06:36.640 pretty low. Ultimately, what countless experts have now agreed upon is that the protein for the RDA

00:06:43.640 has been underestimated because of those reasons. And there have been new studies that have been done.

00:06:49.080 These have been like more stable isotope studies. The major isotope that's used is the L13 carbon

00:06:55.180 labeling phenylalanine, in which case these studies take a small cohort of people, give them a known

00:07:02.620 amount of protein with that isotope tracer. And then that tracer is oxidized when it's metabolized,

00:07:10.000 and that's measured through breath, the oxidation of phenylalanine. And so now you're getting a

00:07:15.420 quantification that's much more accurate in terms of your protein steady state and turnover.

00:07:22.440 And so the whole point here is that you're trying to figure out the minimal amount of protein you need

00:07:27.580 to take in every day to make sure that you're not in a negative protein balance. Why is that important?

00:07:33.320 Well, that's important because we don't store amino acids. We don't store amino acids like we store

00:07:38.400 fatty acids as triglycerides, or we store glucose as glycogen. The major source of our amino acid

00:07:45.080 storage tank, so to speak, is our muscle, skeletal muscle tissue. And you don't want to be pulling

00:07:50.140 from that skeletal muscle tissue to get amino acids every day. Why do we need amino acids every day?

00:07:55.300 Because everything in our body requires proteins. Proteins are doing all the work in our body,

00:08:00.960 and proteins are made up of amino acids. And so we have to be giving ourselves an intake,

00:08:05.880 daily intake of amino acids to make sure we're able to do all those functions.

00:08:09.820 I just want to state that again, because I do think there's a very important and fundamental

00:08:12.480 point here that is glossed over when we talk about it, because we take it for granted. Like if we

00:08:17.660 studied biochemistry and anybody who's studied biochemistry will know this, but we can store

00:08:22.660 fat in unlimited quantities. So if you deprive a person of fat calories for a period of time,

00:08:30.500 they have a long reservoir that they can dig into. Not indefinitely, but they can.

00:08:35.300 We can store carbohydrates. Now, we can't store them quite as much, because we only have so much

00:08:40.080 glycogen we can store in the muscle and in the liver. But when we break down fat, we keep making

00:08:44.920 the substrate to actually make glucose, so we get into a nice little rhythm. But to your point,

00:08:49.820 the only place that an amino acid sits in residence in our body is in the muscle. Therefore, if we even

00:08:59.960 get near the edge where we are not getting sufficient intake of amino acids, we don't have a buffer.

00:09:06.460 We don't have a rainy day fund that we can dip into. We immediately start to catabolize or break down

00:09:13.140 muscle. Now, I don't think we have to make the case that that's a bad idea, but for the sake of

00:09:19.180 completeness, we should state there is not really a single scenario I can think of that is clinically

00:09:24.580 relevant where it would be desirable to give up muscle mass. Maybe if you're Mr. Olympia, you can

00:09:31.120 sacrifice muscle mass. But for you and me, and I think everybody listening to us, giving up muscle

00:09:37.580 mass because we are falling short on our protein intake would be a strategic error and an unforced error.

00:09:44.080 Exactly. For short-term and long-term health, I think that's pretty clear.

00:09:48.540 And that's where this RDA not being enough is a very important point. So let me go back to this

00:09:54.860 isotope tracer studies. Multiple studies, okay? Multiple studies, as you know, have shown...

00:10:00.380 And we'll link to these in the show notes, by the way, just so that people can go and actually look

00:10:04.820 at the papers as opposed to reading about it on social media.

00:10:08.000 Right. Sounds good. Multiple of these papers have shown that really going up to more like 1.2 grams

00:10:14.840 per kilogram body weight per day is what is needed to prevent people, us, adults, from being in this

00:10:21.920 negative protein balance. That's quite a bit more than the 0.8 grams per kilogram.

00:10:26.160 50% more.

00:10:26.600 Right. It's 50% more. So like most of the studies done, isotope tracer studies are between 30% to 50%

00:10:31.000 more. So that's really important because if we look at the actual protein intakes of adults,

00:10:38.220 these are nutritional surveys that are done. Of course, they're all flawed. We can talk about it. I mean,

00:10:42.160 we all know the flaws of questionnaires, but let's just talk about what we think people are actually

00:10:46.940 taking in. Adults are mostly taking in, all adults are taking in about 0.9 grams per kilogram

00:10:53.300 body weight per day of protein. So pretty close to what that RDA is, not what it should be. Older

00:11:00.120 adults, if we look at the gender, male versus female, males are taking in about 0.9 grams per kilogram

00:11:05.100 body weight. Females are taking in 0.8. They're really just hitting that, what we call RDA, which now we

00:11:10.500 have established is not enough. The RDA is not enough to basically be in a net protein balance.

00:11:16.760 So that's really important. And that's essentially telling us that most adults are walking around

00:11:21.760 without being in steady state protein balance.

00:11:25.560 So here's an interesting question, Rhonda. So we know the rates at which muscle mass,

00:11:30.440 skeletal mass are declining by decade in an aging population. Is there any way we can estimate,

00:11:37.520 I'm guessing the answer is no, but on the off chance you would know. So anyway, we can estimate

00:11:41.940 what percent of that decay is simply being driven by insufficient amino acid consumption versus

00:11:49.100 other factors. Other factors would be anabolic resistance associated with aging. Other factors

00:11:54.560 would be anabolic resistance associated with sedentary behavior. Other factors would be lack of

00:12:00.580 sufficient resistance training. Like there are many factors that explain clearly the fact that

00:12:05.280 as a person goes from 50 to 60 to 70, on average, they're losing muscle mass. But it would be

00:12:11.020 interesting to consider how much of that is explained by the fact that they are also barely

00:12:17.280 skirting the minimum amount of nitrogen that they need, and in many cases falling below it.

00:12:22.340 Right. So to answer your question, I don't know that there's a direct way to do that,

00:12:26.040 but I do know that there are studies that have shown that when older adults, so older adults

00:12:31.880 that are really more susceptible to the things that you were saying, like anabolic resistance,

00:12:35.920 where your muscle tissue is not as sensitive to amino acids, mostly because of physical inactivity,

00:12:40.460 which increases with age. But when older adults take in 1.2 grams per kilogram body weight per day

00:12:46.940 of protein, it nearly eliminates some of the age-related muscle loss that happens. So I think that is some

00:12:54.820 evidence to support what you were saying in that if you just increase your protein intake,

00:12:59.960 by 50% to this minimum, what the RDA should be, 1.2 grams per kilogram body weight per day. I think

00:13:06.400 that's pretty much what most all the experts agree. It's time to change that RDA to that number,

00:13:12.240 the minimal amount that you need per day. If older adults just do that, they're actually preventing a

00:13:16.540 lot of the age-related loss in muscle that occurs. And we also know that older women, if they take in

00:13:21.960 that amount of 1.2 grams per kilogram body weight per day, they're 30% less likely to have frailty

00:13:27.640 in old age, which is also very important. So I think that's pretty good evidence that it's clear

00:13:33.800 that just increasing your protein intake by 50% is really important for aging, for our muscle health,

00:13:39.380 and also is getting us out of that net negative state that we're in.

00:13:43.600 So step one is we should move the floor from 0.8 to 1.2.

00:13:47.980 Yes. I think the floor being the minimal amount of protein that we need to take in per day.

00:13:52.720 This is not optimal. We're going to get into optimal, right? This is just the new RDA. And as

00:13:58.200 you mentioned, so you kind of hit on this anabolic resistance. And I think that's also a really,

00:14:02.520 really important point because it does compound with the fact that we're already not getting

00:14:08.300 enough protein to be in a positive state of protein balance. And then you compound that with

00:14:13.940 anabolic resistance. Now, anabolic resistance is when your muscle tissue becomes less sensitive to

00:14:19.720 amino acids. And so you're not making as much muscle protein synthesis isn't occurring as much

00:14:24.920 as it does when you're younger. I think it's pretty consensus now that a lot of anabolic

00:14:29.880 resistance is not necessarily aging, the aging process per se, so much as inactivity.

00:14:37.440 Yeah. And the experiment that Luke Von Loon shared when he was on the podcast, I think was a very

00:14:41.260 elegant way to do this, which is they took young subjects. I don't remember if they were in their

00:14:45.460 20s, but it was thereabouts, maybe in their 30s. So very young subjects. And they put a cast on one

00:14:50.600 leg, no cast on the other. And they left them in this state for a period of time. Again, the details

00:14:55.720 have now completely escaped me, but the point is, has not escaped me, which is after whatever period

00:15:00.860 of time, the individuals were casted on one leg, not casted on the other. Let's just say it was two

00:15:05.280 weeks, four weeks, something to that effect. They removed the cast. Of course, while the person was

00:15:10.200 casted, the casted leg did nothing. The other leg continued to go through exercises. They were

00:15:14.820 doing just single leg, leg extensions, leg curls, things like that. They then ran the stable isotope

00:15:19.780 experiment in these individuals and looked at muscle protein synthesis rates. And lo and behold,

00:15:25.240 the leg that was uncasted, perfectly normal, the other one, significant anabolic resistance.

00:15:32.380 So to me, that's the clearest demonstration that inactivity is the main culprit. There's probably

00:15:38.440 an all things equal age-related component as well, but I suspect that inactivity is playing a larger

00:15:45.480 role than aging per se. I totally agreed. Yeah. I think there's also another study that was done

00:15:51.200 in older adults. Can we explain what anabolic resistance is? I think it's worth people

00:15:54.560 understanding why this idea matters. Yeah. Anabolic resistance, when we eat protein,

00:15:59.060 we're breaking down amino acids and the primary amino acid that is anabolic is leucine. Glucine are

00:16:06.420 getting into the muscle tissue and that is instigating, it's a signal to increase muscle

00:16:11.280 protein synthesis. So you're making more protein in your muscle and that in turn increases muscle

00:16:16.640 hypertrophy. The other major signal to do that is mechanical force. So that would be the resistance

00:16:21.660 training working of the muscles. So as we get older, our muscles do become less sensitive to those

00:16:28.900 amino acids, the leucine transporter being one of the major ways, but I think there's others as well.

00:16:34.480 And so what happens is, is that for the same amount protein dose, and the study has been done,

00:16:40.060 and if you compare younger adults and older adults, 65 years age and older, you give them the same exact

00:16:45.400 protein dose. The younger adults have twice as much muscle protein synthesis. And for the older adults

00:16:51.580 to get the same amount of muscle protein synthesis, they had to double their amount of protein to get

00:16:56.680 the same amount of muscle protein synthesis as the younger adults. That's a lot, double that amount of

00:17:02.300 protein. That's because, again, you need, it's just your muscle tissue is not as sensitive to the

00:17:06.380 amino acids. And so to get more of them in, you have to increase your intake of the protein. Now,

00:17:11.800 to your point about physical activity being the major driver here, I think that's 100%, I agree. I think

00:17:16.940 it's totally true. And there's so much evidence out there to prove that, Luke Van Loon's study being one,

00:17:21.300 but also older adults that do engage in resistance training have the same anabolic response to the same

00:17:28.180 amount of protein as younger adults. So in other words... The activity makes up for it.

00:17:32.300 It does. As you're aging, if you're a 65, 70-year-old male listening to this episode and you're

00:17:39.560 engaging resistance training, you're likely not experiencing much anabolic resistance, maybe a

00:17:44.840 little, but not much. And so you don't necessarily have to experience it if you are physically active

00:17:51.200 in training. And that's really the bottom line here. That's the most important thing.

00:17:54.540 If there's a public health message in this episode, it really is you should be training.

00:18:00.080 Yeah. And think about the impact that physical training has on insulin resistance as well.

00:18:04.680 Completely different mechanism of action probably ties in more to fatty acid accumulation within

00:18:10.100 muscles and all sorts of other things that lead to it. But again, the most effective remedy

00:18:14.900 is physical activity. It's been demonstrated so conclusively that actually nobody really talks

00:18:20.180 about it. It's just taken for granted.

00:18:21.400 It's a good point. So the anabolic resistance, if we're talking about general population,

00:18:26.700 again, we're going back to these surveys that are done looking at how physically active are people,

00:18:30.820 because those numbers are out there, right? We know that generally speaking, adults,

00:18:36.200 including young and old adults, about 32% of them engage in resistance training.

00:18:40.520 How much?

00:18:41.000 32, both young and old. If you just look at older adults, it's 22% of the population.

00:18:47.080 So essentially, most older adults, most people are not engaging in resistance training. They're not

00:18:54.340 doing resistance training. Physical activity kind of mirrors a little bit those numbers. But I think

00:19:00.120 the bottom line here is that putting in the effort, it's harder for people. Putting in the effort is

00:19:05.500 harder. It's easier for them to just increase putting something in their mouth. That's why pills are

00:19:10.420 so popular. People always gravitate towards the easier thing to do, which is, I'm going to eat

00:19:15.680 something. I'm going to put something in my mouth versus putting in the effort. It's unfortunate,

00:19:19.700 but it's a reality. And so I think that even just going back to this RDA being too low,

00:19:25.040 it's just so important. It's so important because people are out there thinking they're getting enough

00:19:30.340 protein. Older adults, younger adults, it's really more important with older adults. You have a little

00:19:34.780 bit of wiggle room when you're younger. And then on top of that, first of all, it's not enough protein.

00:19:40.000 And then this anabolic resistance is setting in and most people are not being active. They're not

00:19:44.400 engaging in resistance training. So there's all these compounding factors that's really just

00:19:48.280 digging into their muscle. It's taking away this insidious sort of taking away each year,

00:19:53.560 each year. And then the next thing you know, you're frail, you have sarcopenia.

00:19:57.000 My patients are obviously indoctrinated into this, but I'm a bit surprised that there aren't

00:20:03.860 more people that talk about this. You do a lot, but the medical system doesn't seem to talk enough

00:20:09.600 about frailty and sarcopenia. And I worry that even when I wrote Outlive, I didn't do enough of

00:20:16.180 a job emphasizing it. I mean, I certainly talked about it, but when I talked about Four Horsemen,

00:20:21.960 I talked about cardiovascular and cerebrovascular disease, cancer, neurodegenerative and dementing

00:20:27.960 diseases, and metabolic disease. Because of course, those are the things that are the main

00:20:31.940 assault on your lifespan. And relative to those, frailty is not as big an assault on lifespan.

00:20:38.900 It is, as you know, the risk of falls are enormous and the mortality is very high once you're north of

00:20:44.940 75. But relative to those four, I had to pick four horsemen, I didn't want to go with five.

00:20:49.840 But when you think about quality of life, which most people care about at least as much,

00:20:56.400 if not slightly more than length of life, I think frailty just kind of wins the day.

00:21:00.940 I think along with cognitive health and minimizing too much cognitive decline,

00:21:06.260 frailty is the thing that seems to determine the quality of your final decade on this earth.

00:21:11.780 Here we have lots of great tools, both in terms of training and nutrition, that can offset that.

00:21:18.120 And yet it is surprising that despite the fact that most people have witnessed it,

00:21:21.980 that's the part that's amazing to me. It's not like the people who are suffering from frailty and

00:21:26.200 sarcopenia are out of sight because they're our parents and our grandparents. We've watched it.

00:21:30.940 We've been to the movie over and over and over again. We see how it goes. And yet somehow we

00:21:35.660 either don't think it's going to happen to us or it somehow still seems abstract because it's so

00:21:40.080 many years off. I mean, what's your take on this overall challenge?

00:21:42.600 For one, I completely agree with the frailty risk being as important, if not more. And

00:21:48.180 witnessing it with like family members, what I think it is, is that it's like this incremental

00:21:52.860 thing where something happens. Maybe there's a fall or maybe there's just a surgery, a planned

00:21:57.820 surgery or a hip replacement or a knee replacement. Your parents or your grandparents are inactive for

00:22:02.640 many weeks and they lose a lot of muscle mass. So this happens. If this is a younger person,

00:22:09.100 it's much easier to gain back that muscle mass. It's not the same with an older adult. It's just

00:22:13.420 not the same. Even if you're engaging in resistance training after, you're not going to get the same

00:22:17.660 amount of muscle mass back as you've lost. And these sorts of events happen in periods of time.

00:22:24.040 There's a planned surgery and there's a fall and maybe there's another surgery or maybe there's

00:22:27.500 COVID or the flu or whatever it is. They keep hitting and you reach this what's called disability

00:22:33.120 threshold where all of a sudden your parents, they just can't walk much at all anymore. And it's

00:22:38.900 like, all of a sudden it's like, when did this happen? Well, the evidence was mounting over the

00:22:43.360 last five years when they had these points of inactivity that were occurring. And so I think

00:22:49.420 people just don't follow the timeline where it's like they see what's leading up to it before this

00:22:55.340 catabolic crisis occurs, where then they reach this point now where they've just lost so much muscle

00:23:00.320 mass from these several events that have occurred where they're just not mobile. And then of course,

00:23:05.620 anabolic resistance is kicking in even more and more and more and everything is just compounding.

00:23:10.580 And I don't think they've observed the timeline and said, oh, A plus B plus C is getting me to this

00:23:15.740 point. And so I think that's kind of what happens. Whereas with Alzheimer's disease, I don't know,

00:23:20.240 it's just like this disease that everyone knows about. And it's like, yeah, this one thing causes the

00:23:24.060 problem. Yeah. Luke Van Loon made a really good point when we spoke, which was when we draw the curve

00:23:30.720 for how people lose strength and how people lose muscle mass, we draw it in a curved smooth line,

00:23:38.960 which gives us the incorrect impression that this is a gradual and imperceptible changing

00:23:46.100 physiologic process. But he goes, that's because it's averaging everything. If you zoom in and look

00:23:52.100 at it at the individual level, it looks like this exactly as you described discrete periods of loss

00:23:58.060 from which there is no recovery. Because at the later points in life, it becomes very difficult

00:24:04.000 to make those recoveries. All of this, of course, points back to where we're going today, which is

00:24:09.500 when you are young and young is 40, 50, even 60, you have to build up as much physiologic headroom

00:24:17.680 as possible. You have to prepare for the rainy day because the rainy day is coming. It's not a question

00:24:24.200 of if. It's simply a question of when and exactly in what fashion it will be delivered. But you must

00:24:29.880 prepare for this. You must steel yourself for what is coming. And you must build up as much muscle mass

00:24:36.360 and strength and cardiovascular fitness as you can muster because the longer you can ride it out,

00:24:43.620 the better you're going to be. The cliff is coming for sure. I mean, it's like your retirement fund.

00:24:47.880 You have to put money in because one day you will retire. And if you don't put any money in that

00:24:53.700 fund, you're going to be screwed. And so with the muscle mass, you're right. You have to bank as much

00:24:58.640 as you can while you're young. And we haven't even talked about optimal. We've just talked about

00:25:03.000 not going backwards, right? Yeah. We've talked about not going backwards, which is what most people are

00:25:07.000 doing because this RDA is too low for one. I think that's the big problem. But optimal is a whole other

00:25:13.800 story. And that's, again, where it's hard to kind of wrap your head around why there's controversy

00:25:20.020 around this. Although coming from the field of aging, I do have somewhat of a, I think there's

00:25:26.640 been a little bit of a nuanced approach to looking at how protein affects the way we age. And I think

00:25:31.700 some of that data has biased researchers and people to think that protein is bad. I think some of it's

00:25:38.000 coming from that evidence, which we can talk about. That's an interesting point. Yep. Yep.

00:25:41.060 Again, aside from that, it's really hard to understand why someone would be so opposed

00:25:46.760 to increasing protein intake when there's really just no evidence that it's harmful,

00:25:52.480 at least in healthy adults. Yeah. I mean, I'd like to talk about harm down the line as we get

00:25:56.960 further up the chain because we've now just, I like the way we're talking about this, where we're

00:26:00.560 going from sort of the 0.8 up to 1.2. And now let's talk about going from 1.2 to 1.6 and 1.6 to 2.

00:26:07.220 And as you continue this journey, let's say you look at the data of which there are some studies

00:26:12.920 looking at three grams per kilogram per day, which I think anybody who looks at the data would argue

00:26:18.360 you're not really getting a benefit at three grams per day that you aren't getting at two grams per

00:26:23.580 day. The curve is saturating. You're hitting an asymptote of muscle protein synthesis at that point.

00:26:29.800 So there may be other reasons a person would choose to consume that much protein, satiety,

00:26:33.420 and things of that nature. But from a purely anabolic reason under normal conditions, let's

00:26:39.320 leave bodybuilding out of it. You're sort of hit the saturation curve, but can't seem to find the

00:26:43.820 evidence that it's causing any harm. This is experimental evidence, even epidemiologic evidence,

00:26:49.200 just no evidence. But that said, let's not get ahead of ourselves. Let's go back to,

00:26:53.240 we've established a new floor. There is nobody that should be consuming less than 1.2 grams

00:26:57.880 of protein per kilogram per day. What happens as we start to increase that from 1.2 to 1.6?

00:27:05.780 This again is where I turn to the experts like Stu Phillips. In fact, he did a really great meta

00:27:10.920 analysis looking at about 49 different studies in adults that were undergoing controlled trials,

00:27:17.980 resistance training alone or resistance training plus supplemental protein. And the supplemental

00:27:25.320 protein went up to 1.6. Well, actually it went up above that. But what was really found in that study

00:27:32.580 was that even going from like 1.2 grams per kilogram body weight per day, obviously, to 1.6 grams per

00:27:41.300 kilogram body weight, people gained about 27% more lean body mass and 10% more muscle strength compared to

00:27:49.160 just training alone. Same training, just adding the protein. That's pretty big.

00:27:53.600 I was going to say that is bigger than I would expect, especially on the strength side.

00:27:57.940 In the strength side. So the protein itself, but if you think about it in a way,

00:28:02.140 we're talking about supply and demand. So now we're talking about more optimal, a little more

00:28:06.840 optimal. We're talking about people that are training. That's number one. You need to be

00:28:10.620 training. If we're talking about optimal protein intake, you need to be training. And then what's

00:28:15.540 happening when you're training is you're breaking down muscle. You need protein to support the repair of

00:28:19.780 that muscle and the rebuilding of it. And so that makes sense in a way. But yeah, I was surprised

00:28:24.860 by the strength as well. Really, once you went above 1.6 grams, there was still increases in

00:28:32.380 muscle protein synthesis.

00:28:32.880 Yeah, but the curve is slowing down.

00:28:34.540 I like the analogy that Stu Phillips uses. He says like, if you have like a wet washcloth,

00:28:39.840 you squeeze it to get all the water out. Most of that water is coming out at 1.6 grams per

00:28:44.220 kilogram body weight. But you can keep squeezing a little and you're still getting some water

00:28:48.080 out. It's just marginal. It's like most people don't care about that difference. Some people do.

00:28:54.460 Now, let's say you're someone that's obsessed with banking muscle mass. You're going to care

00:28:58.940 about that. Let's say you're a high level athlete, definitely going to have to go above 1.6. That's

00:29:05.180 when you get into the more 2, 2.2 grams per kilogram body weight. So people that are doing a high level

00:29:10.140 of training, whether that's endurance or strength training, resistance training, because endurance

00:29:14.600 athletes, I mean, you are battling being catabolic. I think the evidence for more optimal, you're

00:29:20.600 talking about 1.6 grams per kilogram body weight. You can get marginal benefits above that, up to like

00:29:27.400 2, 2.2 grams per kilogram body weight. But again, that's people that are really training.

00:29:31.480 Yeah, to me, there's an analogy here with ApoB and cardiovascular disease. So if you look at the

00:29:38.620 three bodies of evidence, so if you look at all of the epidemiologic data, if you look at all of the

00:29:42.900 clinical trial data, and if you look at all of the Mendelian randomization data, and you plot every

00:29:48.200 single one of them on a graph, and there's a beautiful graph, which we'll include in the show

00:29:51.940 notes, that does this. So on the x-axis, and it's done in LDL-C. Again, LDL-C, ApoB, easy to view them

00:29:58.780 together. So on the x-axis, you have LDL-C going down. So from 160, 140, 120, 100, 80, 60. So descending

00:30:07.340 LDL-C, and on the y-axis, you have mortality, cardiovascular mortality. So not surprisingly,

00:30:14.360 all of these point down. As LDL-C goes lower, cardiovascular mortality goes lower. What's

00:30:20.560 interesting, though, is you can see that there are different points in the curve at which it starts

00:30:27.340 to matter more. And at some point, it flattens out. You don't get as much benefit from reduction.

00:30:32.060 And so we could use the same argument of, well, what is optimal? Because we're doing the reverse

00:30:36.480 here. Here, lower is better as opposed to going up on protein. But Peter Libby has done an analysis

00:30:42.760 that has demonstrated that you will continue to see a meaningful reduction in cardiovascular disease

00:30:47.760 as ApoB heads towards 30 milligrams per deciliter. 30 milligrams per deciliter is really low by most

00:30:53.800 people's standards. For context, 60 milligrams per deciliter is about the fifth percentile at the

00:30:59.860 population level. 30 milligrams per deciliter is about what a child is. So we're born with relatively

00:31:04.840 low levels of ApoB. And as we age, they just keep going up and up and up. Which, of course,

00:31:09.340 is one of the things that's driving cardiovascular disease is this rise in ApoB. So the question then

00:31:14.780 becomes, how low do you need to go? Should everybody be walking around at 30 milligrams per deciliter?

00:31:20.660 Is that the solution to eliminating ASCVD? And the answer is probably not. It probably depends on your

00:31:25.800 previous exposure, though. So if I have a patient who's already had two stents placed and has a

00:31:32.020 significant burden of disease, you bet your bottom line they're at 30 milligrams per deciliter of ApoB,

00:31:38.060 even if we have to put three drugs on them to make sure that's the case, because their burden of

00:31:42.480 disease and their lifetime exposure to ApoB has been so high. But if I have an individual who's 40

00:31:48.740 years old, who has perfectly pristine coronary arteries and is walking around with an ApoB of 60

00:31:53.980 milligrams per deciliter, I don't think you need to do a thing. I think they're just fine. And again,

00:31:59.120 it's the inability, I think, for people to understand that level of nuance and understanding

00:32:03.140 when it's worth the second squeeze versus when just the sloppy squeeze is good enough.

00:32:09.100 It's very frustrating for a person like me who craves nuance.

00:32:12.480 Agreed. I love that analogy. I think it's perfect because I do think most people that are training

00:32:18.320 probably are getting a great amount of benefit from 1.6 grams per kilogram body weight. But that

00:32:23.520 doesn't mean you can't go above that and still get a little more benefit. Certainly, when you start to

00:32:28.600 get into that energy deficit phase as well. So we were talking about elite endurance athletes,

00:32:34.980 that's one way to be in an energy deficit. But there's also people that are actively trying to

00:32:40.400 lose fat, gain muscle. If you want to lose fat and gain muscle at the same time,

00:32:45.020 you're going to have to take in a lot of protein.

00:32:47.580 Yeah. So that's another very important point. Another point I want to make is

00:32:50.180 you're still dealing with an asymmetric target. We tell our patients to be closer to two. Now,

00:32:56.940 I know that's just going to get a whole bunch of people on the anti-protein train,

00:33:00.660 just losing their mind. I can just see the phosphorylation going off right now as they're

00:33:05.720 watching this clip. How is this guy so irresponsible to tell his patients to eat two

00:33:12.500 grams of protein per kilogram of body weight? Didn't he just hear what Rhonda said? 1.6 is good

00:33:18.620 enough for most people. Well, my patients unfortunately don't live in labs. Unfortunately,

00:33:23.740 Rhonda, my patients live in this place. It's called the real world. And in the real world,

00:33:27.960 you can't always hit your targets. Some days you do, some days you don't. Some days you're traveling,

00:33:32.980 some days you're not. Some days you can figure it out, some days you can't. So if I'm telling

00:33:38.600 somebody to hit 1.6 and one day they're at 1.2, another day they're at 1.7, another day they're at

00:33:43.920 1.5, another day they're at 1.9, on average, they might hit 1.6. But how many days were they below

00:33:50.720 versus how many days were they above? Let's just say it's an equal split. But we've just established

00:33:55.340 the shape of this curve is like this. So that means every day you're below, the downside is

00:34:02.880 much greater than the upside of being above. In other words, all the days you're above are not

00:34:08.500 making up for all the days you're below. So what I'd really like to do is shift the range so that

00:34:15.200 your low day is 1.6 and your high day is maybe 2.2. And then guess what? You don't have days

00:34:23.640 where you are ever, ever amino acid restricted. And this is the difference between people who

00:34:30.880 take care of people in the real world and bozos who write on Substack who don't know the first thing

00:34:37.780 about clinical medicine when it comes to managing athletes and people who have to fend for themselves

00:34:43.780 every day with every meal. And this is why I'm so tired of talking about this, but I feel we need

00:34:49.740 to talk about it. If you're sitting there listening to this and you're confused and you're asking,

00:34:53.560 oh my God, should I be eating two grams per day? Yeah, more or less. And that way, if you fall short

00:34:58.380 at 1.6, you can be confident that you're okay. But if you're aiming at 1.6 and you have a bad day

00:35:04.340 and you will, when you hit 1.2, you might be taking a step backwards and you won't make up for it the

00:35:09.080 next day. I can just tell you from personal experience, it's actually smarter to aim higher

00:35:13.560 because I'm constantly not meeting the 1.6. I am not. This is the thing. People look at me like

00:35:18.580 I'm a protein eating machine, which first of all, I'm not. But secondly, I have a hard time hitting

00:35:23.700 my goals too. I'm busy. I miss meals. Sometimes we just have a low protein meal. Like for whatever

00:35:30.420 reason, my kids want to have pasta for dinner. We literally have pasta and sauce. There's no fricking

00:35:35.280 protein in this anyway. So it's very difficult if you don't have a chef preparing your every meal.

00:35:41.600 And I never have a chef preparing any of my meals unless I'm out at a restaurant

00:35:45.620 to hit these targets every day.

00:35:47.620 Right. I was thinking about this because we mentioned the 1.2 being the sort of the minimum

00:35:51.680 buy-in. The 1.6 grams per kilogram body isn't necessarily just for people training a little

00:35:57.640 bit. It's also older adults that are not training because we talked about the anabolic resistance.

00:36:02.400 I'm needing twice as much protein as well. And so what you're talking about here is going up to two

00:36:07.780 so that you can really have an average at least of 1.6. You're getting that average.

00:36:12.880 I never want to fall below that. That's really the point is I know I'm training every single day.

00:36:18.060 Now, am I training like a madman? No. But seven days a week, I'm either doing some form of cardio

00:36:23.060 or something in the gym. So it's just, I know that I'm going to take steps backwards if I'm below 1.6.

00:36:29.240 So I'm going to overshoot so that my down day is 1.6. And if my up day is 2.5 once in a while,

00:36:37.100 who cares? Because that gets to the next point. Show me the data. Show me the data that eating 2.5

00:36:44.040 grams of protein per kilogram per day is even remotely harmful. I'm still waiting for it.

00:36:49.660 I'm still waiting for the data. David Allison wrote a piece on LinkedIn recently where it was

00:36:54.300 a call to anyone. Just show me the data that meet these criteria. Human clinical trial of this

00:37:01.040 duration, da-da-da-da-da. Nothing but crickets. Yeah. I mean, I haven't seen any human data

00:37:06.820 either, for sure. The most negative data I saw recently was a study that looked at total

00:37:12.800 parenteral nutrition in ICU patients where the question was, hey, should we be ramming high amounts

00:37:18.300 of protein in these people? And the most negative thing you could say is it had no benefit. And that's

00:37:22.480 interesting. So maybe we shouldn't be ramming high protein, total parenteral nutrition into the

00:37:27.080 central veins of critically ill ICU patients. But it didn't harm them. And if anybody's going to be

00:37:32.280 harmed, I would think it's the people that are in renal failure. Yeah, exactly. I haven't seen that

00:37:37.420 data either. We haven't spoken specifically about pregnancy or adolescence. What do we know about

00:37:43.680 protein requirements? Because there are clearly women listening to us right now who are pregnant or who

00:37:47.740 will be pregnant. And I don't think there are any adolescents listening to us, but I bet there are

00:37:51.240 parents of adolescents. So what kind of guidance would we want to give these folks?

00:37:55.240 It goes up with pregnancy and also adolescence. I mean, so- Are there formal recommendations?

00:38:00.840 I don't remember. Again, it's all about like going a little bit above what's the RDA. And we've

00:38:05.860 already established that's not enough. So, I mean, honestly, I think if people are listening to this

00:38:10.860 episode, just knowing that 0.8 grams per kilogram body weight per day is just not enough.

00:38:16.360 So if we accomplish nothing else, that's the single most important take-home message here.

00:38:20.080 I really think it is because everyone looks at those guidelines.

00:38:23.620 Yeah, it's really funny. The other day I was eating something and I forget how much protein

00:38:28.200 it had in it, but it had percent of daily requirement, but it was obviously baked to a

00:38:32.840 very low number. Because I remember my son was looking at it with me and he goes, I forget what

00:38:36.780 the number was. Is that really like 40% of your daily protein requirement? And it was a relatively,

00:38:40.660 and I said, no, but I just didn't have the energy to explain the RDA to him. So I was like,

00:38:46.560 no, this is just wrong. You can ignore this.

00:38:49.100 Growing is also an important time for protein, right? Because these amino acids and the essential

00:38:54.940 amino acids are activating IGF-1 growth hormone, and that's really important for growth. I know

00:39:00.420 there were studies done in like infants and toddlers that were given egg versus milk versus

00:39:07.140 some kind of vegan protein. And it was clear that the egg was the winner here. Giving protein with more

00:39:13.520 essential amino acids was important for growing taller. And that's always something that I, as a

00:39:18.580 mom, think about, right? I'm always trying to get protein in my son. Plus, the kids are more active.

00:39:23.200 Kids are more physically active. They're doing sports and things like that, adolescents. So it's really

00:39:28.400 important to get the protein requirements. I haven't dug into all the nuance of that data. The way I look

00:39:34.900 at it is it's got to be like a 1.2, even though that's in the adult, it's more like a 1.2 gram per

00:39:40.180 kilogram for an adolescent who's pretty close in body size to an adult. Generally speaking,

00:39:45.640 they start growing pretty tall. Yeah. I mean, I would think for kids, it should be at least

00:39:49.320 the 1.2 to 1.6. Just look at the activity level of my kids is they make me look sedentary. Okay.

00:39:56.040 Anything else we want to say on the topic of protein to help with some of the confusion that

00:40:02.580 is out there? I think we should talk a little bit about some of the misconstrued understanding of

00:40:07.620 mechanisms of action around mTOR, cancer, and stuff like that.

00:40:11.840 I would say the other thing would be the calorie restriction, people doing intermittent fasting,

00:40:16.780 people doing anything if they want to do body recomposition, the gaining of muscle and losing

00:40:22.120 fat. I think that is a very specific group of a population of people where the high protein

00:40:29.060 intake is critical. Because if you're in a caloric deficit, you really are battling

00:40:34.800 your body pulling from your muscle reserve. If you're resistance training, that helps somewhat,

00:40:39.960 but you're certainly not going to gain muscle. And we just talked about wanting to bank as much

00:40:43.980 muscle as possible as we're younger while we can, right? Because we need that reserve because

00:40:49.340 we're going to start pulling from it eventually. And so I think that that's where you start to get

00:40:54.040 really high numbers, 2.2, even higher. You can find studies out there, it's like three grams per

00:40:58.820 kilogram per body weight. Going above the 1.6 in this scenario seems to be key as well. You're

00:41:04.540 getting up to that 2.2 grams per kilogram body weight per day because it does give you a little

00:41:09.600 bit more edge over gaining muscle, muscle protein synthesis in combination with resistance training,

00:41:14.940 as well as it's like you mentioned, it's satiating, a little bit thermogenic. I don't know that that's

00:41:19.900 the big mechanism here, but I think the big mechanism here is just you're really wanting to prevent this

00:41:25.080 catabolism. So I think that's just another important point because there are a lot of people

00:41:29.420 that do intermittent fasting, time-restricted eating. They're trying to do body recomp,

00:41:33.660 gain muscle, lose fat. I think a lot of people are interested in that.

00:41:36.960 There was one period of my life when over the course of a year, I made a very dedicated goal to

00:41:42.440 lose body weight and gain muscle. So I wanted to see like, could this be done? And it did require

00:41:49.440 quite a bit of intermittent fasting or time-restricted eating, I suppose, to be more accurate.

00:41:54.000 But the amount of attention I had to pay to protein intake was pretty incredible. And what I did that

00:42:02.120 seems counterintuitive because I wasn't intermittent fasting because I believed that a fasted state was

00:42:07.620 producing some benefit. There's some people who think that, well, if I don't eat breakfast, I'm

00:42:11.240 kicking off some autophagy or something. No, no, it was purely a caloric restriction ploy.

00:42:16.080 So my fasting window did not prevent consuming liquid protein. In other words, if I wasn't eating

00:42:23.180 breakfast or lunch, which I wasn't, I was only having a meal a day, which was dinner,

00:42:27.540 but I would still consume protein shakes outside of those windows. Otherwise I could never hit the

00:42:32.260 protein target. So I was in a caloric deficit, but an amino acid excess. And again, you can actually do

00:42:40.320 that with liquid protein pretty easily because basically all you're getting is getting relatively

00:42:44.940 few calories because you're just consuming whey protein.

00:42:47.720 Did you have any like GI problems consuming so many shakes?

00:42:51.140 No, but I did a lot of experimentation. So ultimately I settled on a brand. I'm blanking

00:42:55.760 on the name of it now. I have no affiliation with these guys and I'm blanking on their name.

00:42:59.640 A scent maybe? Does that ring a bell? I really liked them. Again, I'll give them a shout out because

00:43:04.240 one, it was the only protein I found I could mix directly in water and not have it be lumpy. I didn't

00:43:10.340 even need a blender. This sounds silly, but the hassle of me having to like wash a blender twice a day

00:43:16.040 was sometimes an impediment to not making a shake. So just to be able to put the scoop or two scoops,

00:43:21.060 I would usually put into a glass with water and mix it with a fork and actually drink it and have it be

00:43:25.860 totally fine and not lumpy. I don't know how they do this, but it was amazing. It actually tasted fine.

00:43:32.080 I don't like sweet drinks that much, but it was not too sweet and absolutely no GI issues at all.

00:43:38.000 Whereas sometimes the pure egg proteins, I didn't like the feeling on my gut. So for whatever reason

00:43:42.580 that worked for me, but to your point, it's another level of challenge if you're trying to

00:43:47.600 recomp in that way. Or people on GLP-1, right? Receptor agonists, right? And I don't know how

00:43:53.460 difficult it is to eat a meal versus like take a protein shake. You're satiated pretty much all the

00:43:59.040 time. You don't have a real appetite, but also digestion is slowed. So if you're like consuming

00:44:03.620 more protein, I don't know how that all affects. We've seen in our patients, I get asked this all the

00:44:08.380 time. I would say 15 to 20% of our patients are on trisepatide. And unlike five years ago when we

00:44:17.280 started using semaglutide in patients and we're just watching muscle fall off these people. And

00:44:23.660 frankly, my point of view five years ago was, I don't know about these drugs. I think there's

00:44:28.040 some benefit in some people, but I think there's a lot of downside. I today think that virtually anybody

00:44:33.780 can use these drugs safely by safely. I don't just mean in the obvious sense of the word. I mean

00:44:38.380 safely for long-term muscle health as well, but it requires a ton of deliberate attention. So I'm

00:44:45.620 glad you brought it up. This is exactly the group of people who you want to be using easy to digest

00:44:50.900 protein sources. And if you're on trisepatide, you don't really want a steak. You don't really want

00:44:57.140 to have a big chicken breast. You might not want to even have an omelet, but if we have to make sure

00:45:02.060 you're hitting that 1.6, you might be doing a bunch of liquid shakes. And yeah, we can sit here

00:45:08.080 and poo-poo processed food and say, how disgusting is it that people have to resort to eating shakes?

00:45:13.600 Okay, fine. But if the alternative is they're not getting enough protein and they're on a drug that

00:45:19.380 is making them anorexic, we also know the downside of that. Well, the answer is clear, right? You don't

00:45:24.780 want to be losing muscle mass for sure. My point is we do DEXA before and after. We're not seeing the

00:45:31.040 type of muscle loss we saw with our V1 approach to this. What kind of dose? Are they on like a

00:45:36.860 higher dose? No. I mean, I think for trisepatide starts at 2.5. Some people are getting enough

00:45:42.660 benefit there. I mean, the other thing that I think our approach has been is that slow and steady wins

00:45:46.800 the race. So we've seen anecdotally some data. I've heard from others and we've seen it as well

00:45:54.500 that yo-yoing on and off these drugs is probably a bad idea. So I always tell a patient, look,

00:46:00.880 I'd probably rather you were on 2.5 milligrams until there was a new drug that we felt was even

00:46:06.340 better than you're on 10 milligrams. You lose a ton of weight. You come off, you gain, you go back on,

00:46:12.420 you lose. The idea of being on a saw is probably a bad idea. I think the data suggest you're getting

00:46:19.180 most of the value by about 10 milligrams. So once you go to 12.5 and 15, which are the two

00:46:25.000 highest doses, you're still getting a benefit, but it's like most drugs, you're getting most of

00:46:29.560 the benefit at the lowest dose. So 5 to 7.5 milligrams of trisepatide is probably where you're

00:46:34.000 getting the majority of the benefit. I'd much rather a patient be sort of slow and steady on it as

00:46:39.280 opposed to try to go for maximum and rapid weight loss. What do you think about some of that data on

00:46:44.640 like heart issues or bone loss? Does that concern you at all? Sure. I think it all does. I mean,

00:46:50.740 I think all of this stuff has to be paid attention to. And I think the question again, comes back to

00:46:54.960 how much of that is occurring due to training, how much of that is happening due to the loss of

00:47:00.520 amino acid intake and the loss of training. Or the neuropsychiatric, that's another one,

00:47:05.740 the eyes. What I'm interested in is we have these GLP-1 receptors like on so many different tissues

00:47:11.800 systemically. Like how is it beneficial? Is it not beneficial? I don't know that we really know.

00:47:17.700 We have data where there's obviously positive effects. You see like reduced Alzheimer's disease

00:47:21.980 incidents with people taking these GLP-1 receptor agonists. But how much is that? Is it due to like

00:47:26.420 weight loss? We've looked into this a lot because it's funny, we did a podcast on this somewhat

00:47:31.060 recently where I went through this particular question, which is, will GLP-1 receptor agonists

00:47:38.420 ultimately prove to be gyroprotective. I came up with a very obscure way to define that, which is

00:47:44.260 independent of weight loss. Because obviously at the macro level, they're going to be gyroprotective

00:47:49.920 because if you apply them to people with type 2 diabetes and significant obesity, and you correct

00:47:54.820 the metabolic dysfunction, you're going to live longer. So by that regard, it's a gyroprotective

00:47:59.700 agent. But the real question is, if you take a person who is of normal weight, who does not have

00:48:05.240 type 2 diabetes, but maybe has a higher risk for Alzheimer's disease, and you microdose them,

00:48:10.120 so you're giving them 2.5 milligrams per day, which by the way, we are doing in some patients

00:48:15.460 for obscure metabolic condition without obesity. So we have patients who have diabetes, but are

00:48:22.920 already at very low body weight. We have two patients actually in our practice in this regard.

00:48:27.120 After lots of detailed back and forth machination with Ralph DeFranza, who's a previous guest on

00:48:32.680 the podcast, we sort of realized that at least one component of the drug regimen for these patients

00:48:37.680 was going to be a GLP-1 agonist. Now, it seemed very counterintuitive to give trisepatide to people

00:48:43.460 who have a BMI of 23, but we've been able to do it without them losing weight. So again,

00:48:50.200 very careful strategies around nutrition and the effect on their diabetes is profound.

00:48:55.560 They're looking more metabolically healthy.

00:48:56.700 Oh my God. These are really interesting cases that maybe at some point, obviously in a de-identified

00:49:01.180 way, it would be interesting to talk about where you have OGTTs that are unrecognizable. Like you

00:49:05.760 simply cannot believe the degree of metabolic dysfunction in a person who otherwise looks the

00:49:10.540 way they look. And in one case in particular, it was so confusing that even after all the genetic

00:49:15.880 testing we did, like we simply couldn't figure out an answer for this. We couldn't understand where

00:49:20.040 the beta cell fatigue was coming from absent a formal diagnosis of type 1 diabetes. And within

00:49:25.700 three months of being on 2.5 milligrams of trisepatide, this individual's OGTT had almost

00:49:31.480 normalized. And I suspect by about six months, it will.

00:49:35.640 That's fascinating.

00:49:36.700 And we've managed to do this without any weight loss. So this to me is the interesting question,

00:49:41.440 which is when you look at some of the Alzheimer's biomarkers, which are improving,

00:49:46.220 improving significantly, it begs the question, should this be part of the playbook for an individual

00:49:51.200 who's at high risk? Especially given that we now, I think, really understand how to make sure people

00:49:55.980 don't lose weight and don't lose lean mass. And therefore, I suspect don't lose bone density and

00:50:00.720 all these other things that matter.

00:50:02.220 Or like you said, if you're doing this microdose, maybe you're not going to be as satiated. Like

00:50:08.220 you'll still have somewhat of an appetite because you're on such a low dose. Maybe you're going to

00:50:12.100 have a little bit of an effect.

00:50:14.140 We've also seen some other weird things anecdotally. Patients have told us that when they inject in the

00:50:18.900 abdomen, the fat, the sub-Q fat of the abdomen, basically the anorexic effects are greater than

00:50:24.460 if you inject in the leg or butt. And we looked into this and there was some mechanistic data to

00:50:28.660 suggest that maybe you're getting more vagal tone when you inject in the abdomen. Again,

00:50:32.840 I just don't know if any of these things are correct. They would need to be studied. But again,

00:50:35.940 that would be a very important piece of data. If there's a location, you can inject this where

00:50:39.760 you minimize the anorexic effect of the drug. Again, for some people, that would be a feature,

00:50:45.660 not a bug. For some people, that would be a bug as opposed to a feature. So you have to

00:50:48.720 understand how to use the tool.

00:50:50.580 Yeah. This just reminded me of something that we should have pointed out. Talking about the

00:50:55.180 protein requirements, grams per kilogram body weight. I do think it's important, like we were

00:50:59.980 just talking about obese people.

00:51:01.120 Yes, I'm glad you brought this up.

00:51:02.500 Yeah, exactly. Where it's like, most people aren't going to do a DEXA scan to see what their

00:51:05.920 lean body mass is. But ultimately, I think, and I've talked to a variety of experts, Brad Schoenfeld,

00:51:10.700 Sue Phillips, they agree that really, if you're someone that's overweight or obese, you shouldn't be

00:51:15.060 calculating it based on your actual weight because your protein requires way too high. It's more like

00:51:19.680 your target weight. If you empirically could measure your lean body mass, that would be better.

00:51:24.060 But yeah, I just wanted to point that out.

00:51:26.020 Yep. And I'm glad you did. So that's right. For most people, probably not much of an issue. But

00:51:31.160 if you're at 300 pounds right now, and your ideal body weight is 220, you don't need a DEXA to figure

00:51:37.880 that out. A DEXA can help. But most people who are 300 pounds remember, gosh, at the end of high

00:51:44.020 school, I was 220. That was my good weight. Or maybe, you know, at the end of high school, I was

00:51:48.320 200 pounds, which is, I'll probably never get back into those genes again. But by the end of my freshman

00:51:53.460 year of college, I was 220. That was kind of a good weight for me. And then it's just kind of gone

00:51:57.360 downhill from there. You had this orthopedic. There's the story of how you got to be 300 pounds.

00:52:02.340 Yeah, most people can figure out. 220 is probably my goal weight. Exactly. And that's what I should be

00:52:06.560 targeting. Yeah. So you made a great point, which is how do we reconcile the following? So caloric

00:52:15.520 restriction as an intervention, as a geoprotective intervention is the oldest one in the book. I'm not

00:52:22.740 really aware of an intervention where a non-genetic intervention that has, from a longer standing

00:52:28.700 perspective, produced a more consistent outcome in terms of laboratory animals, where you restrict

00:52:33.280 them of calories and they're going to live longer. So again, to my knowledge, there are only two

00:52:37.740 interventions that have extended life across all four models of organisms from yeast, worms, flies,

00:52:46.800 and mammals, rodents. And that is caloric restriction and rapamycin. And they have something in common,

00:52:53.260 which is they both result in the downregulation of mTOR. So we also know that an amino acid you just

00:53:02.260 mentioned a moment ago called leucine is the single most important of all the amino acids at turning

00:53:10.440 up mTOR. So how can we reconcile the idea that protein seems to be good for you, but mTOR going down

00:53:19.600 seems to be good for you, at least in another way? Well, for one, I'm being very facetious because you

00:53:24.960 know I know the answer to this question. And it's like, oh gosh, where do we start? Because let's ignore

00:53:31.540 the worm and the fly and all that because who cares? I mean, even the rodents, it's a stretch.

00:53:36.320 You know what else turns on mTOR? Exercise. Physical activity, mechanical force turns it on

00:53:40.880 in our muscle. And we know exercise is like one of the best things that we can do for our health.

00:53:45.780 I think here, I think for simplicity, the best way to think about this is that you want mTOR active

00:53:51.320 in your skeletal muscle. You want it active in your skeletal muscle. You don't necessarily

00:53:55.900 always want it active systemically, but if you are exercising, if you're moving around

00:54:02.760 and you're taking in your protein, it's going to your muscle. We know that for a fact. I talked

00:54:08.600 about anabolic resistance and how exercise can counter that while it's increasing the leucine

00:54:13.840 transporter, the expression of leucine transporter. It's causing leucine and other branch chain

00:54:19.060 amino acids to go up into skeletal muscle. Multiple human studies have shown this. These are

00:54:23.720 tracer studies, beautiful data, no argument. Exercise causes leucine and other branch chain

00:54:30.500 amino acids to be taken up into skeletal muscle, where you want it to be so that it activates mTOR,

00:54:36.000 increases muscle protein synthesis. When it comes to deactivating mTOR, whether that's through protein

00:54:43.200 restriction or rapamycin, that would be like an hours-long podcast talking about all the nuanced

00:54:50.280 data there because there's all sorts of differences with sex differences in rodents.

00:54:54.980 You're aware of all this data. My biggest thing here with the protein restriction, let's talk about

00:54:59.100 one. I did spend six years in grad school working with mice. I did a lot of animal studies. These

00:55:04.500 mice are in a small cage. They are not physically active. They are not running around. I mean,

00:55:10.360 they move a little bit. They're not under threat. They're not under threat. They're being fed ad libitum.

00:55:15.400 They're just being fed up as much protein as they want. Perfectly thermoregulated. They're not being

00:55:19.460 exposed to influenza or COVID, whatever viruses, anything that's going to take them out for a

00:55:25.040 period of a couple of weeks. They're in a sterile environment. They're happy. They're happy and

00:55:29.660 that's it. People are not mice. We talked about earlier, as we get older, we're being exposed to

00:55:36.100 infectious diseases. Things are going to make us immobile for a period of weeks. And that is devastating

00:55:41.740 to us, especially when you add them up and they happen this year. And then the next year, it happens

00:55:46.140 again. And then you're just losing that muscle mass. And then you reach that disability threshold.

00:55:51.360 We talked about Luke Van Loon talking about those curves. It's very clear. I mean, you can see the

00:55:55.780 data where there's a disability threshold. You get enough of these catabolic crisis events where you're

00:56:00.700 just immobile for a certain period of time because you've had a surgery or you've had the flu or whatever

00:56:05.640 has kept you inactive. That doesn't happen to these mice. So protein is much more important

00:56:11.120 to humans because we, of course, need that muscle mass and we need to bank it early. We've established

00:56:17.260 that. And I think that's a really important difference here is that we can't just look at

00:56:22.000 the data in mice and go, oh, you can restrict them from protein and they live longer and they're fine.

00:56:25.840 Well, they're not going through these catabolic crises. They're not going through these points of

00:56:30.180 not moving for a period of time for like losing all this muscle mass and then not happening and they

00:56:34.540 reach this disability threshold. And then it's very different. So I think that's first and foremost

00:56:40.340 important to point out. The second thing is, is that if we're talking about protein intake,

00:56:46.600 I think that you and I agree the optimal scenario here isn't a sedentary person just sitting there

00:56:52.940 eating as much protein as they want. No, they need to be moving physically active. That's the whole

00:56:57.700 point. You're supporting your physical activity by increasing your protein intake. And so in that

00:57:03.980 scenario, again, the amino acids that are activating mTOR are going to skeletal muscle. Like that's been

00:57:09.740 shown. Leucine is going into skeletal muscle. So who cares if you're taking in more?

00:57:14.900 I think that's such an important point, Rana, that I would even go one step further, which is if you

00:57:18.420 told me come up with the optimal nutrition strategy for the individual who is active and then come up

00:57:24.900 with the optimal nutrition strategy for a person who is going to be sedentary, they would be very

00:57:29.580 different. I'm going to try to talk that sedentary person into not being sedentary. But if at the end of

00:57:34.720 the day, I can't, if that individual says, I don't want to do anything, I just want to sit in front of

00:57:39.920 my computer, you know what? It probably makes sense to be a little bit caloric restricted because I

00:57:45.160 can't solve your metabolic challenge through activity. But what if I could at least solve it

00:57:50.960 through nutrition restriction? Again, I think it's the inability of people to understand that those

00:57:57.260 are very different states. You cannot treat those two people the same way.

00:58:00.700 Right. There was a study by Walter Longo, of all people, like years ago, came out. It was a large

00:58:06.260 cohort study looking at dietary protein intake from vegetable versus meat sources. And we all know

00:58:13.740 that meat sources have higher levels of essential amino acids like leucine. All-cause mortality was

00:58:19.620 looked at. And the same statement that you've heard millions of times from other studies about,

00:58:24.800 okay, vegans have a lower all-cause mortality than meat eaters. Well, it turns out when you actually

00:58:29.220 start to analyze the data and correct for a lot of confounding factors, meat eaters that were

00:58:35.000 physically active, were not obese or overweight, didn't smoke, didn't drink excessive alcohol. So

00:58:41.200 in other words, they didn't have all these unhealthy lifestyle factors. They had the same mortality rate

00:58:45.960 as the vegans. So I think that also is a good point here where it's like, okay, if you're going to be a

00:58:50.600 sedentary person that's smoking and if you have unhealthy lifestyle factors, maybe you don't need to be so

00:58:56.340 obsessed, you definitely want to make sure you're at least getting the minimal amount of protein

00:58:59.500 because you don't want to be in the deficit. But you don't want to necessarily just be constantly

00:59:03.900 activating mTOR if you're just going to sit around and smoke and be overweight and not do anything

00:59:07.900 with that protein. Yeah. And the other thing I think that is missing from this discussion,

00:59:12.240 this is where I think inflammation serves as a great analogy. So I think most people on the surface

00:59:17.680 understand that a constant on state of the inflammatory system would be bad. But of course,

00:59:24.000 if you had no inflammatory response, that would be also bad. So the ideal state is inflammation when

00:59:30.640 you need it, otherwise off. Inflammation when you need it, otherwise off. And I think that's probably

00:59:36.460 the right way to think about this, which is we want mTOR on when it has a job to do and we want it

00:59:43.620 relatively silent when we don't. And I think if rapamycin is gyroprotective, and when I say if,

00:59:51.300 I mean in humans, I think it's unambiguously protective across most species, but we still

00:59:56.100 don't know if the species of interest is going to benefit from this drug. And we may never, by the

00:59:59.780 way, but it's probably working by tamping down the chronic inflammatory component of what we see with

01:00:07.860 mTOR activation, which by the way, might actually involve inflammation as well as one of the many

01:00:11.700 things. So there's also this challenge of trying to get folks to understand the difference between

01:00:16.060 chronic and acute things. Cortisol, great example. So cortisol, vital hormone, the appropriate rhythm

01:00:23.180 of cortisol is essential for life. If you took that away, you would actually be dead. That's called

01:00:27.920 Edison's disease. But cortisol constantly being on would also be a problem. That would be Cushing's

01:00:33.480 disease. So both extremes, bad. It's do you know when you need it and what it's supposed to do? And I

01:00:40.260 think the same is true with mTOR. I'd also like to see data comparing, even if it's animal data,

01:00:46.360 comparing giving rapamycin or inhibiting, somewhat inhibiting mTOR versus physical activity, making

01:00:52.280 them run on a treadmill, being physically active. Because if you look at a lot of the protective

01:00:56.240 effects of rapamycin, I'm like, this is what exercise does. And exercise does it better. So I'm

01:01:02.080 just not convinced that someone who's already bought into like how important exercise is,

01:01:06.900 both cardiovascular and weight training. Well, Eric Verdon made a very interesting

01:01:11.220 comment on my podcast a while ago. And so Eric is in the camp that he does not believe RAPA will be

01:01:17.340 gyroprotective in humans. And he talked about the longevity quotient. So for listeners, the longevity

01:01:22.500 quotient is a plot, a very famous plot that on the x-axis puts body size and on the y-axis puts lifespan.

01:01:30.460 And you just plot all the organisms on this thing. And as a general rule, it rises up and to the right.

01:01:35.740 The larger an animal is, the longer it lives. And it's a pretty straight line. In fact,

01:01:40.620 we should find a good example of it and link to it in the show notes. But there are always

01:01:45.940 animals that punch above and below their weight. So there are animals that fall off that line,

01:01:51.760 either too high. So these are animals that live much longer than you would expect based on their

01:01:56.280 body size. And there are animals that punch well below their body weight. They live much shorter

01:02:01.000 than they should based on their body weight. Well, it turns out two interesting examples are

01:02:05.080 mice and humans. Mice live on average two years. I forget the exact number. They should be living

01:02:10.480 close to four or five years, I think, based on the longevity quotient line. So they are punching

01:02:14.980 well below their weight. And humans, we live 80 years. We should probably be 40, according to

01:02:20.860 the data. By the way, we did live 40 years until modern medicine came along. So maybe we were totally

01:02:26.700 on the curve correctly until medicine 2.0 came around at the turn of the last century. And

01:02:31.300 basically over five generations doubled our lifespan. Eric argues, I think this is a very

01:02:35.940 interesting argument, rapamycin disproportionately works well in animals that are below the longevity

01:02:41.700 quotient. So that's why it works so reproducibly in mice. But he argues it might not have any effect

01:02:48.680 in humans because we've already captured so much of our genetic potential in terms of lifespan now

01:02:54.180 that the idea that RAPA would give us an extra 15% of life, he feels is just kind of hard to

01:03:00.940 imagine. And again, there's a theoretical argument. It's super interesting, but I'd never heard it in

01:03:06.560 relation to the longevity quotient before. And I thought it was very much worth pondering.

01:03:10.400 Yeah. Well, that's interesting. I've also seen data with rapamycin given to people that were

01:03:15.060 undergoing resistance training and it like blunted, obviously, some of the muscle protein synthesis

01:03:19.580 as would be expected. I don't remember the dose of rapamycin. It wasn't super, super high.

01:03:24.460 But to me, that was like enough to be like, well.

01:03:27.660 Yeah. And then the question, of course, is, is there a way around that? Is there a way where

01:03:31.340 you could intermittently dose it? You just take it once, you time it so that it's not in proximity to

01:03:36.560 about a resistance training by a couple of days or something like that. But yeah, there's a lot there.

01:03:41.640 Great expression I heard recently, which is mice usually lie, monkeys sometimes lie. It's humans we care

01:03:48.880 about. I thought it was just fantastic.

01:03:51.680 Well, to get back to the mTOR story, I think that recent study, I don't know, it was in the last

01:03:55.520 couple of years that came out. It was the animal study where they gave mice 25 grams of protein and

01:04:00.860 mTOR was activated in macrophages. And it was like, this whole story was pieced together about-

01:04:05.820 25 grams of protein?

01:04:07.640 Sorry, maybe it was the equivalent dose.

01:04:09.040 Equivalent, okay, okay.

01:04:09.720 It was the human equivalent dose.

01:04:10.920 I was like, wow, they're eating their body weight in-

01:04:13.280 The human equivalent dose was 25 grams, yeah. But it was essentially like arguing that atherosclerosis

01:04:18.820 was being caused by protein. I'm like, are you kidding me? Like, for one, we know atherosclerosis,

01:04:26.340 the bigger story there, is not protein. But again, it comes down to this whole activating mTOR

01:04:31.980 in systemic circulation versus the leucine going to the muscle because you're physically active.

01:04:38.740 And keep in mind, those transporters, the leucine transporters, they're pretty sensitive for

01:04:44.000 quite a while. I mean, you're talking about at least 24 hours, maybe even longer, but definitely

01:04:48.700 24 hours.

01:04:50.000 I think the mice atherosclerosis studies are very dangerous. We have to be very careful.

01:04:54.860 They have a very different lipoprotein system than we do. They evolved in a totally different

01:04:59.140 manner than we did. The amount of protein they require is totally different from us. So I'm

01:05:03.780 always really wary when I see these studies that are using the mouse model of atherosclerosis.

01:05:08.740 I understand why we do it because it's much easier and cheaper than looking at primates.

01:05:13.080 And obviously, we can't do these studies in humans. But you can find a lot of things in mice when it

01:05:18.460 comes to atherosclerosis that don't seem to matter whatsoever in human biology. I would chalk this up

01:05:22.860 to one of those examples.

01:05:24.400 So then there you have it. I mean, that's a lot of the controversy around protein being bad for you

01:05:29.720 and activating mTOR is coming from that study. And then there's countless studies on cancer

01:05:34.340 increasing with IGF-1 and mTOR. And again, same deal where IGF-1 exercise is causing IGF-1 to go

01:05:41.140 into the brain, to go into muscle.

01:05:42.980 People also don't appreciate how short the half-life of IGF-1 is. It's a staggeringly

01:05:48.100 short half-life molecule.

01:05:49.720 Oh, really?

01:05:50.220 Oh, yeah. It's insanely short half-life.

01:05:51.700 What's the half-life?

01:05:52.100 When administered systemically, it's on the order of minutes.

01:05:56.780 Okay.

01:05:57.360 Yeah. And by the way, administering IGF systemically is a lousy way to get it to the muscle.

01:06:02.040 You want to think of it almost as a paracrine thing where it has to be delivered into the muscle.

01:06:07.140 So look, all roads for me still point back to this idea that, and I know you would agree with

01:06:12.780 me, so it's not going to be that controversial, but exercise is the most important drug. I'm just

01:06:17.740 not aware of a drug, in quotes, that is better than exercise. And I know there's this enormous

01:06:24.260 effort to figure out a way to put exercise into a pill. I just can't imagine it'll ever happen.

01:06:29.100 It's not.

01:06:29.520 There might be several pills that come out of it. We might figure out a way to make clotho. We

01:06:34.220 might figure out a way to make BDNF. We might figure out a way to deliver IGF directly to muscles.

01:06:39.760 There might be a whole bunch of little things.

01:06:41.620 There's like 500 molecules that change.

01:06:43.160 Yeah. I don't know if you remember this. I'm dating myself, but I don't know if you remember

01:06:46.120 irisin. Yeah. Yeah. Like, I mean, there are no shortage of these things.

01:06:50.360 Right. There's so many things going on, for sure, that is beneficial with exercise. And

01:06:54.640 just to kind of bring it back to the protein, I think that they go hand in hand. We're talking

01:06:59.220 about being optimal, increasing our health span, increasing our lifespan, having a good quality

01:07:04.100 of life, then you're talking about having a higher protein intake to support your physical

01:07:08.100 activity, period. Athletes. They're some of the longest-lived individuals on the planet.

01:07:13.460 We talked about this in our last podcast. Olympic athletes live on average five years longer

01:07:17.580 than the gen population. Same goes with a lot of these athletes playing these indoor team

01:07:21.720 sports. And there are several studies out there looking at elite athletes, including people

01:07:26.680 in the NBA, Major League Baseball, a lot of these big professional sports leagues. They're

01:07:32.780 taking in at least two grams per kilogram of protein per day. So clearly, protein isn't killing

01:07:40.040 them. In fact, they're living longer than the general population. So again, it comes

01:07:44.120 down to that. Exercise is the king, right? Exercise is the most important thing, but you

01:07:48.120 need a protein to support that physical activity. And I don't understand why anyone's arguing about

01:07:54.740 that. What's the argument?

01:07:56.460 Despite all the flack I'm taking, I'm going to just defend this one and continue. And by the

01:08:00.460 way, if new data emerge, I'm always happy to change my mind. I've changed my mind about

01:08:03.840 so many things. It is absurd the number of things I've changed my mind on. I've changed my mind

01:08:08.000 on GLP ones. I've changed my mind on saunas. I mean, I can count the list of things I've

01:08:11.780 changed my mind on over the past 10 years. If there are data that will make me change

01:08:15.360 my mind, I will stand up here with a straight face and I will eat crow and I will tell you

01:08:19.720 that I've changed my mind. But I'm going to stand by my recommendation. Two grams per kilogram

01:08:24.300 per day. And my rationale, again, I explained it earlier in the podcast, but just to restate

01:08:29.640 it, if you aim for two on the day you fall short, you'll still be at 1.6. If you aim for

01:08:35.140 1.6 on the day you fall short, you'll be 1.2. And that 1.2 won't be made up for on the

01:08:40.620 next day because the downside is asymmetric compared to the upside. So that's our recommendation

01:08:46.400 clinically. And that's how we work with real people in the real world, not on our sub stack

01:08:52.540 pages to try to help them live a longer life. Yeah. Is there anything else with the protein?

01:08:57.940 I mean, no, let's never talk about this again, pending new data that fundamentally changed the

01:09:04.360 way we think about it. All right. I want to pivot to another topic, which you may be single-handedly

01:09:10.380 more responsible for the buzz on this topic than anybody else I can think of. And that is

01:09:15.040 creatine. So should we start with, well, first of all, just tell me what got you interested in this

01:09:20.680 topic? You're not the typical demographic, no offense intended by that, but when I was in high

01:09:25.740 school, right, and I'm probably 15 years older than you, we as young boys in high school in the

01:09:31.740 eighties were mainlining creatine like it was our day job. But here's the thing. I don't remember

01:09:38.400 why it must've been. Cause your friends were doing it. Well, no, no, but it must've come from

01:09:41.760 bodybuilding magazines. Like I don't know where we got the information. I was thinking about this the

01:09:46.000 other day. Cause I knew we were going to talk about this and I was like, okay, there was no

01:09:48.520 internet. What was our source of truth? It was muscle and fitness. So there must've been something

01:09:54.920 in muscle and fitness that told us this. And then, you know what I realized we did? We would hang

01:09:58.960 out at supplement stores. We'd literally go in and the supplement stores always had some big bro in

01:10:05.100 baggy pants that tapered down to his feet and he was barely wearing a shirt and he was yoked and he

01:10:11.040 was explaining to us. And we were like at the altar of this guy and he was telling us there's creatine

01:10:15.800 monohydrate and then there's like creatine phosphate. And at the time everyone said creatine

01:10:20.180 phosphate is better. And you have to load 30 grams a day for two weeks. Then you go into your

01:10:26.140 maintenance phase at five grams a day. And then you repeat the cycle every eight weeks or whatever

01:10:30.400 it was. And we were like buying this stuff by the truckload. And this is like almost easily 35,

01:10:36.480 40 years ago. Fast forward, I don't know, a few years ago, we're paying attention to creatine again.

01:10:42.560 You just made a really important point and I'll talk about my journey in a minute. And that is,

01:10:46.040 it's one of the most well-studied sports related supplements ever. There's just decades and decades

01:10:53.740 of research out there on creatine. A lot of it has to do with muscle. We'll talk about the brain,

01:10:59.380 which is my interest, but it's one of the tried and true. I mean, it's safe. I don't know that

01:11:04.440 there's any other sports supplement out there that's as safe as creatine. I don't think there

01:11:08.220 is. That's an important point. My journey with it began with my obsession with increasing my

01:11:14.900 resistance training. Like your performance or your hypertrophy or your recovery? What specifically?

01:11:19.660 Everything that we talked about in the first half of this episode, where I realized that I was so

01:11:25.140 focused on endurance training for long-term health, for brain health, that I sort of neglected my

01:11:31.800 muscle mass and thinking about how important muscle mass was for long-term health.

01:11:36.060 You've chronicled this pretty well on your social media. You've got videos of you deadlifting,

01:11:40.200 like you're really embracing this.

01:11:42.100 Yes. Yes.

01:11:42.760 Awesome.

01:11:43.140 After having a couple of experts on and just, when I have an expert on, I read the literature

01:11:47.400 voraciously. Like I just dive in. I want to be in it. And it's part of the fun. I love it. I get to

01:11:53.160 learn all this new material that I'm interested in. And so I finally realized that I wasn't doing

01:11:58.940 enough training, resistance training. I have a personal trainer now. I'm doing resistance type

01:12:04.580 training. I do like a CrossFit type training for at least three hours a week I'm doing now.

01:12:09.380 It started out, I was doing like 30 minutes a week. So I've gone from 30 minutes to like three hours

01:12:14.960 a week. Big difference. And that's when I became really interested in creatine where I was like,

01:12:19.920 okay, I know this one supplement is obviously like shown to benefit people that are working out.

01:12:27.540 I didn't know why everything until I got into the literature, but that's kind of what got my interest

01:12:31.260 into creatine. Most people know creatine is stored in our skeletal muscle as creatine phosphate,

01:12:37.360 and it's essentially used to rapidly recycle ATP, adenosine triphosphate. This is the major energy

01:12:46.340 currency in our cells. And creatine phosphate is able to help rapidly recycle that so you can make

01:12:53.080 energy quicker. Very relevant for a lot of scenarios, including high-intensity interval training,

01:12:58.120 resistance training, even endurance training because it decreases recovery time because you're

01:13:02.700 recycling that ATP. So it's really relevant for a lot of scenarios. And we do make creatine

01:13:09.300 endogenously. That's another thing where it's like, this is a molecule that we make in our body.

01:13:13.380 It's not like a dangerous thing that I'm really scared of. We make about one to two grams in our

01:13:18.400 liver. Our livers make about one to two grams a day. And then we can take in another, depending on

01:13:22.160 how much meat we eat, meat is the major dietary source of creatine. So vegetarians 100% rely only on

01:13:29.320 their one to two grams a day. And they're probably the population that benefits the most with

01:13:34.980 supplementing with creatine. And there's just countless studies out there showing this because

01:13:39.440 they're just not getting anything from their diet, essentially. I mean, there's like negligible

01:13:43.980 whatever is in plants. Does the type of meat matter? Does fish versus beef versus chicken? I would

01:13:48.640 imagine there are differences. Yes, there are. There are differences like beef. Beef would be the most.

01:13:52.500 Yeah. It's probably why people on a carnivore diet, they just get so jacked, right? They're

01:13:58.700 getting the creatine, they're getting the protein, and they're working out. And it's like this

01:14:02.000 combination, right? They're just getting so much. And do you have a sense of if you eat a 12 ounce

01:14:05.960 steak, how many grams of creatine would you get in there? People can figure that out with Google.

01:14:11.560 Generally speaking, that like on average, people are getting in their diet probably like one to two

01:14:16.200 grams. Additional. Yeah. So you've got your endogenous plus. Yes. Yeah. And then you can supplement

01:14:21.500 on top of that. And this is where I would say for many, many, many decades, the literature was all

01:14:27.260 about the effects on exercise performance because the muscle is a big consumer of energy, especially

01:14:34.000 if you're working the muscle. And so I'm totally just summarizing this. I'm not going into every

01:14:40.580 single detail, but generally speaking, five grams a day of creatine is enough to saturate your muscle

01:14:48.620 tissue. It takes about a month, maybe three weeks to actually fully saturate it if you're doing five

01:14:54.300 grams a day. Hence the bros that were telling me to take 30 when I was 13. That might've been

01:15:00.500 overkill. Yeah. It's coming from the fact that in these studies that have been done, because people

01:15:05.540 haven't been taking the five grams a day for like three weeks and they're doing this short-term

01:15:10.180 weeks-long study, they want to like quickly get their muscle saturated. And that's why they do that

01:15:14.580 loading phase. And so most people don't have to do that unless you're like doing some competition

01:15:19.440 and you like need right then and there. Generally speaking, it's just not necessary. And you really

01:15:24.600 just increase the risk of GI distress. And our thinking today is just take five every day and

01:15:29.940 then you should be all right. Well, that was my thinking up until a few months ago. And I was

01:15:34.460 taking for the last year and a half, I was taking about five grams a day. The evidence there is that

01:15:40.940 the creatine is essentially improving your exercise performance in that you can do one to

01:15:48.200 two more reps or essentially the volume of training goes up because you're recycling that energy

01:15:53.440 quicker. You're able to do more. And that is why you then get gains in muscle mass and strength.

01:15:58.660 It's not like the creatine itself is acting like protein. It's not increasing muscle protein synthesis

01:16:03.660 if you're just a couch potato. Yep. You have to do the work. You have to do the work. Right. And the

01:16:08.620 reason that you do increase the muscle mass and strength is because you're able to do more work.

01:16:13.320 It's pretty obvious. Anyone that for me with my CrossFit, it really is useful because there's a lot

01:16:17.940 of explosive training, a lot of HIIT. So for me, it was pretty obvious that it was having an effect.

01:16:24.120 And of course, there's probably a mixture of placebo in there as well. I'll definitely admit that.

01:16:28.820 But then I started getting interested in some of these brain studies. As you know, I'm very interested

01:16:33.420 in brain health, neurodegenerative disease risk, anything that can improve cognitive function

01:16:38.000 in a safe way, like any kind of safe nootropic. And that's where I really started to get interested.

01:16:43.820 And this has built up over years where I was getting interested in the brain effects,

01:16:47.920 even though I hadn't been supplementing with it. I had been keeping an eye on the literature.

01:16:52.360 And finally, when I started using it, I got pushed over. I'm like, okay, I'm all in. I want to get into this.

01:16:57.260 You felt like you got all in because you actually felt a difference or you were like, well, look,

01:17:01.620 I'm already taking it for these muscle purposes. Let me really now go deeper on the cognitive science.

01:17:07.560 Yes. I was already like, first of all, the literature was clear with the muscle. There's a lot of literature.

01:17:12.700 You can't deny it. You just can't.

01:17:14.720 It is a little odd. There aren't that many things that show up where the consistency of the studies

01:17:19.500 is always in the same direction. And really what you're basically looking at is the magnitude or the effect size.

01:17:24.520 But you're always on the same side of the tornado plot.

01:17:27.600 Exactly. Right. And when we're talking about 40 years or whatever of research, that's a lot of data.

01:17:32.960 With the brain, so for one, your brain does make a little bit of creatine as well. Something

01:17:37.300 I don't remember. I think it's somewhere between one to three grams a day.

01:17:40.880 But the data on the effects of supplemental creatine on the brain isn't dating back as far. And so

01:17:47.440 you do have to kind of take the data with somewhat of a grain of salt because there's a lot of small

01:17:53.620 studies. And they're not like, you can't hang your hat on it. This is the end all be all.

01:17:58.360 And let's talk about some of the measurements. I think one of the advantages of studying the

01:18:02.120 effects of creatine on physical performance is we have really good objective measurements that

01:18:07.800 you can demonstrate in a short period of time. You can do a 12-week study. And in just 12 weeks,

01:18:12.520 you could objectively, unambiguously determine if there was hypertrophy and if there was an increase

01:18:18.620 in performance. How do we do that on the cognitive side? What are the data that you've been

01:18:23.020 looking at that have given you an increasing level of confidence?

01:18:26.360 Okay. Well, first let's talk about dose because that's important. And I think that that was where

01:18:31.140 initially when researchers were looking into like the effects of creatine on the brain,

01:18:35.980 the five grams a day didn't seem to be doing anything in terms of getting creatine into the

01:18:41.780 brain.

01:18:42.560 Creatine is crossing the blood-brain barrier that's established?

01:18:45.100 It is. However, the muscles are greedy as hell.

01:18:49.100 Ah, those lovely greedy muscles.

01:18:51.020 Yeah, the greedy muscles. When you're taking in up to about five grams of creatine,

01:18:56.520 they're consuming it. They're taking their share.

01:18:59.100 Especially if you're training.

01:18:59.880 If you're training, it's like, yeah, exactly. But even if you're not training,

01:19:03.260 it's still going to muscle. But yes, especially if you're training. And so there was a German study

01:19:07.560 that was published a few years back that did dose-dependent effect and looked at creatine

01:19:12.700 levels in certain brain regions.

01:19:15.360 Naive question. Are they using an isotope? Are they labeling the creatine?

01:19:18.600 I believe they were using an isotope. They're not using CSF levels or anything.

01:19:22.380 I believe it was an isotope.

01:19:23.620 Okay.

01:19:24.200 But don't hold me to it because I don't remember exactly.

01:19:26.960 You mean more creatine.

01:19:27.680 I know.

01:19:28.020 But 10 grams was where creatine was now...

01:19:32.720 Was not rate limited.

01:19:33.900 Yeah, exactly. Now you were increasing levels of creatine in the brain. I'm pretty sure it was

01:19:37.260 isotope labeled. Essentially 10 grams...

01:19:39.640 You have to double it.

01:19:40.380 You have to double that. And that's where I was like, okay.

01:19:44.520 Does that mean that you're going to get mixed results if you look at the

01:19:48.380 cognition literature because you're going to have some studies that were underdosed? And if you have

01:19:52.500 a study that was done at five and it shows no effect, you're going to come to the wrong conclusion

01:19:56.460 potentially.

01:19:57.060 Bingo. Just like with any supplement and or drug dose matters. So yes, that is the case. But also

01:20:03.600 it's important to point out, just like with muscle, you have to be stressing your muscle for creatine to

01:20:09.560 work. You're basically putting in the work and you're able to put in more work. And that's why you

01:20:15.060 can increase muscle mass and you can increase strength. With the brain, it works in the background of

01:20:20.760 stress. And what I mean by stress is sleep deprivation, psychological stress, like you have

01:20:27.280 an exam, marital. I mean, whatever psychological stress, emotional stress, sleep deprivation is a

01:20:32.600 big one, neurodegenerative disease, or anything that's compromising brain function. That's where

01:20:38.320 creatine really shines in terms of cognitive function. And we'll get into measurements. But I

01:20:43.400 think that's important to point out. This is my argument. I feel like I'm constantly under stress.

01:20:48.220 I think most people are constantly under stress.

01:20:50.960 Anybody listening, if you're not under stress, I'd like to hear from you. I want to know what

01:20:54.740 you're doing.

01:20:55.360 Same. Same. Even just like diving into the scientific literature, what we do every day,

01:21:01.440 learning, that is the stress. The brain consumes a lot of energy as well.

01:21:06.740 20% of our total caloric intake goes to an organ that weighs less than 2% of your body weight.

01:21:13.480 It is the most insane statistic of the human body.

01:21:17.220 Totally. Which is why it makes sense that giving your brain extra creatine, which can recycle that

01:21:24.760 energy quicker, would help, particularly in the background of when you're using more of that

01:21:29.560 energy. If energy is being triaged to whatever stress and the hormones and the whatever, whatever's

01:21:34.520 going on, fill in the blank. And so the studies that typically are looking at the effects of creatine on

01:21:39.660 cognitive function are looking at processing speed. They're looking at a battery of tests that are

01:21:45.440 typical of any fill in the blank supplement or treatment that is either going to improve cognitive

01:21:52.240 function, memory being another one, right? Processing speed's a big one too, I would say,

01:21:57.040 that creatine's been shown to improve. But again, really it's in the background of stress,

01:22:01.940 whether that's stress being aging. So older adults. So aging is kind of a stress, brain aging.

01:22:07.800 So older adults seem to benefit from taking exogenous creatine or supplemental creatine

01:22:13.220 and people that are sleep deprived. That's another one. That's a really big one. In fact,

01:22:18.180 there's been a few studies that have shown people that are sleep deprived, if you give them,

01:22:24.380 this was on a per kilogram body weight basis. So I think total, it was like 20 to 25 grams of creatine

01:22:32.000 that were given just based on their body weight. But if they were sleep deprived and given that creatine,

01:22:37.360 not only did the cognitive deficits that usually occur when you're sleep deprived not occur,

01:22:42.480 but their cognitive processing speed was improved more than baseline. Now, this is a small study.

01:22:47.380 If you, Peter, were to go to the study and look at this, you'd be like, this is a small study. And I

01:22:51.880 agree. We can't just hang our hat on this one study. Who's doing these studies? Because there can't

01:22:57.720 really be any financial incentive to do them. Creatine is ubiquitous. There's no IP around it.

01:23:03.240 I want to give people some advice on how to go buy creatine. Because if you go to Amazon,

01:23:07.240 it's like, which one do I buy? But who's sort of taken the mantle on trying to understand this?

01:23:11.900 Because it is an important question. And if you've got something that's insanely cheap,

01:23:15.940 completely safe, has other benefits in the body anyway, and all we're really trying to figure out

01:23:21.240 is, hey, should we all just be doubling our dose from five to 10? It'd be great to quantify the effect

01:23:26.120 size and stratify patients that we need to be reaching out to. Because again, not everybody listening to us

01:23:31.420 is doing this anyway. And it's just one more thing to ask somebody to do, which comes at a cost.

01:23:37.360 There's a psychic cost to just asking people to do more stuff. And it's one more thing you got to do.

01:23:43.320 Again, this is like low hanging fruit in the world of biomedical research.

01:23:46.860 It is. Darren Kandow is someone who he's getting into the brain stuff. I think there's quite a few

01:23:52.160 people that have been doing muscle research who are now, it's opening doors for them where they're

01:23:57.380 like collaborating and they're reaching out to like people that are doing more neuroscience and

01:24:02.980 it's kind of exploded.

01:24:03.820 This has got like Dom D'Agostino's name written all over it.

01:24:06.000 That's a really good point. It totally does.

01:24:07.300 We got to talk Dom into doing this.

01:24:09.160 So there was like a pilot study that came out. These are researchers that I don't know necessarily,

01:24:13.520 and some of them are pretty junior. But there was one that came out with people with Alzheimer's

01:24:18.220 disease and they were given 20 grams of creatine and it improved cognitive function in these

01:24:23.640 patients with Alzheimer's disease. I think there was also placebo control as well.

01:24:27.800 And then they took those same patients and then had them exercise and improved strength and

01:24:32.180 improved lean body mass.

01:24:33.800 I'm just going to be skeptical. I still think that the name of the game is prevention,

01:24:37.840 where I'm most interested. And of course, that's the hardest thing to study.

01:24:40.660 But when we think about the energy crisis that is happening in a brain with Alzheimer's disease,

01:24:47.060 and while there are, I think you and I would agree, there are probably many paths towards AD.

01:24:51.600 There are inflammatory paths, there are lipid mediated and vascular paths,

01:24:55.660 and then there are sort of these more metabolic paths. But when you take that individual who is

01:24:59.900 most susceptible to the metabolic path towards dementia, and 10 years earlier, or 20 years

01:25:06.080 earlier, you're giving them a substrate that is augmenting ATP creation. Yeah, I get it. That's the

01:25:12.320 hardest thing to study. That's also the single most important question in my mind.

01:25:16.140 Totally. Prevention is the name of the game for sure, 100%. Unfortunately, there's a lot of people's

01:25:21.080 parents out there that have it right now because they missed the boat on prevention, right? Those

01:25:26.420 people are obviously, their kids are willing to do anything to help them. It's terrible, right?

01:25:31.220 I think the reality here and the point I want to make is I think that creatine for the brain is the

01:25:36.400 most interesting aspect of this area of research right now, at least for me. I certainly think that

01:25:42.160 there's really no downside to doing 10 grams a day. Now, in some cases, sleep deprivation,

01:25:46.680 like I just got back from China about five days ago. I've been like doing 20 grams a day, 15 to 20.

01:25:52.380 I remember as a kid, I never had the GI side effects with even 30 a day. But for some people

01:25:57.060 is 10 to 20. In one dose, it would probably affect a lot of people's GI. I do five gram doses.

01:26:04.780 And you'll just put the five grams into water and... I'd put the five grams into water or like tea,

01:26:10.300 and then I just take it like that. And I do it mostly before noon. I don't know if this is placebo,

01:26:17.440 but I don't get sleepy in the afternoon anymore. If I only get five grams, I get the sleepiness.

01:26:23.380 Now, again, it could be complete bias. And who cares? If it's not...

01:26:27.100 If the placebo is working for you, take it.

01:26:28.580 Exactly. Because it's physiologic, right? I mean, it's a biological mechanism that's working for me.

01:26:34.240 And if you listen to this episode and it works for you, that's great because there's really no

01:26:37.440 downside. And in fact, I think we're going to get more and more evidence out there that it's

01:26:41.300 going to be beneficial and 10 grams is going to be the new five grams. Yeah, it's going to be the

01:26:46.380 new baseline. But if you aren't in this state of jet lag, 10 grams per day, you do two shots of

01:26:52.100 five and you're feeling great. That's what I do. 10 grams a day.

01:26:54.380 Let's talk a little bit about brands. Are most of the companies out there that are otherwise very

01:26:58.980 reputable in making supplements? So whether that be Thorne, Momentous, like I've lost track of all the

01:27:04.180 names of the companies out there that make supplements. There are a handful of supplement

01:27:07.180 companies that actually really seem to be credible. Do you have any difference between

01:27:11.200 them? Do you always look to make sure that CreaPure is the active ingredient within it or does it

01:27:15.460 matter? I think the most important thing is that it's creatine monohydrate. The reason people like

01:27:19.500 CreaPure is because it's like pure. But what I like even more than that is NSF certification because

01:27:26.020 there's rigorous testing to make sure there's no lead contamination and these heavy metals and things

01:27:31.640 that sort of hitchhike on a lot of these supplements. Personally, that's what I look for. I think

01:27:36.700 CreaPure is great too, depending on whatever brand is using CreaPure.

01:27:40.480 Yeah. Lots of brands are using it.

01:27:42.020 Exactly. So NSF is what I look for. I use the Thorne.

01:27:44.240 And there's no reason you can't have both. You could have CreaPure in an NSF certified product.

01:27:47.860 Totally. For sure.

01:27:48.640 One thing I want to call out that one of the members of my team was sharing with me yesterday,

01:27:52.280 apparently there are a whole bunch of creatine gummy products out there. And for the obvious

01:27:57.960 reason, they're very popular, but there was a third party test. Well, why don't you tell what

01:28:03.940 they discovered?

01:28:04.720 Yeah. I mean, it was essentially, there was third party testing looking at actually quantifying

01:28:09.720 the levels of creatine monohydrate in these gummies. And there was essentially none in 95%

01:28:16.440 of them. And that does, I think, translate to gummies in general. I've talked to vitamin

01:28:21.520 manufacturers and they've said it is incredibly challenging to get an active ingredient into a

01:28:28.420 gummy and you're heating it up. So there's the heat component that's degrading things.

01:28:33.000 So gummies, unless you can find a third party tested gummy that actually has the amount of

01:28:40.040 creatine monohydrate in it that says on the nutrition facts label, I would avoid a gummy.

01:28:44.540 Yeah. And also the thing about this whole gummy craze that drives me bananas is you have to ask

01:28:49.480 the question, how many gummies do I need to eat? So look at the chalky white creatine powder. Look at

01:28:55.320 what five grams looks like and ask yourself, how many gummies would I need to put this into such that

01:29:01.820 they would be palatable? And then the question is, do I really want that many gummy bears?

01:29:05.980 What am I doing to my teeth?

01:29:07.480 Yeah. What else is in the gummy?

01:29:08.700 How much sugar do I need to eat? That's totally unnecessary. Like if I'm going to have sugar,

01:29:12.800 let it be good. Give me a nice piece of chocolate. Give me a piece of carrot cake.

01:29:16.780 I'm not going to squander my sugar calories on gummy bears that are not even giving me creatine.

01:29:21.340 Don't eat the gummy. Like you need the powder. Thanks for bringing that because also capsules,

01:29:25.820 you're going to have to take so many capsules to get, I say the 10 grams or even the five,

01:29:29.280 if you're just looking for the muscle effects, you're just going to have to take a lot of

01:29:32.460 capsules. And so that's also an important point. I also think that the vegan thing and vegetarian

01:29:38.180 is another really important aspect. If you take them to 10, they should be fine because they're

01:29:42.920 at least offsetting the couple grams. No, I'm just saying it'll change.

01:29:45.320 I have so many vegan friends that it's literally changed their lives. My phone blew up. I mean,

01:29:50.500 I couldn't believe the magnitude of the fact that these women were experiencing was way outsized

01:29:55.880 compared to what I was getting. And I noticed an effect. I mean, it was like unreal.

01:30:00.160 And how long had they been vegan?

01:30:02.000 One of them, not that long, maybe like two years, but the other one just decade.

01:30:06.840 Yeah. And so I'd be interested, the one who had been vegan for two years when she all of a sudden

01:30:11.300 got creatine back, I wonder if that was a short enough period of time that she was like, oh my

01:30:14.620 God, this is what I used to feel like just two years ago, or there's probably too many confounding

01:30:18.160 variables.

01:30:18.480 You know, she's always kind of calorically restricted too. And I don't know how much protein she was

01:30:21.900 really eating when she wasn't, wasn't. Yeah. But that's a good question.

01:30:25.540 Talk to me about kids. So my daughter is 17. She's really training hard. I mean,

01:30:30.560 she runs cross country. She does track. She's in the weight room. Is she too young?

01:30:34.820 Should she be taking creatine?

01:30:36.920 Yes. There's studies out there on kids, children, like younger than 17.

01:30:41.420 My boys who are very active in sports.

01:30:44.060 Okay. How much?

01:30:45.240 If I remember correctly, it's like 0.1 grams per kilogram body weight.

01:30:48.460 I give my son two and a half grams. Again, there's studies out there. It improves agility

01:30:55.820 is a big one and speed. So a lot of these studies were done more like an endurance because kids

01:31:00.720 aren't like lifting weights. So it improves agility and speed.

01:31:03.780 And would you, for my daughter, give her five?

01:31:06.180 Yeah. She's tall too.

01:31:08.000 She's studying hard. Like, does she just need the full 10?

01:31:10.440 Exactly. Exactly. She is almost an adult.

01:31:13.880 I think she's done growing.

01:31:14.860 For me, I would do 10. If it was my daughter. There's actually some studies that have been

01:31:19.620 done in college students who are taking a test and stuff. And of course, you're sleep deprived

01:31:24.380 when you're studying for the test and the creatine improves test score. So I'm all in on the creatine.

01:31:29.760 My creatine budget, literally the household creatine budget just went up by 4X.

01:31:33.680 Same happened to me like six months ago or so. Again, the harm that people like claim is unfounded.

01:31:40.100 The kidney problems. First of all, as a physician, you know what the problem is. People are looking

01:31:43.960 at creatinine. If you're like supplementing with creatine, you got to tell your physician.

01:31:48.140 Well, the other thing is, physicians listening to this, please make this another reason to just

01:31:52.820 look at cystatin C, please. I'm sure the test costs an extra dollar. It's worth it. Cystatin C is a far

01:31:58.460 more accurate way to measure and estimate GFR. And you don't have this problem of getting the

01:32:03.320 confounded creatine levels increased. I know we have to get you out the door relatively soon because

01:32:09.340 you were giving a talk today. But if we have a little bit more time, I want to talk something

01:32:14.720 about a topic that is near and dear to both of our hearts, which is temperature.

01:32:18.800 You know my journey on the sauna train. I was probably the biggest sauna skeptic for many years,

01:32:24.000 not because I didn't love it. I've always loved a sauna. I just had a hard time believing that the

01:32:28.220 data were causal. I was just like, there's too much healthy user bias in here. But over the last five

01:32:34.100 years, as I've looked closer and closer at the data, while I can't comment on the effect size,

01:32:39.160 I think it's very difficult to comment on the effect size from all the epidemiology.

01:32:43.120 It's very difficult for me to believe that there isn't a positive effect in terms of at least

01:32:48.520 cardiovascular disease and dementia. Those are my priors. My priors are, I'm now in a place where I

01:32:53.620 actually view sauna as an intervention that can help an individual reduce their risk. And for me

01:33:00.540 personally, because I don't really worry about cardiovascular disease anymore, it's so easy to manage

01:33:04.080 the risk around that otherwise. But dementia is a very difficult risk to manage because there's

01:33:09.940 fewer things we understand about the causal pathways to get there than we do ASCVD. So in

01:33:15.280 many ways, I'm in the sauna, not just because I enjoy it, not just because it's a wonderful social

01:33:19.400 opportunity to be with your spouse, if that's how you choose to do it, but because I'm also banking a

01:33:24.260 little bit on, hey, I want to get some benefit to my brain. So tell us where you are currently,

01:33:29.200 because you're one of the people who I think keeps up with this literature more than anybody.

01:33:33.500 Tell us if anything has changed in your mind one way or the other, both in increasing confidence,

01:33:38.900 decreasing confidence. Just update us on where you are.

01:33:41.860 Yeah. I am still a huge proponent of using deliberate heat exposure to improve your health,

01:33:48.040 both cardiovascular and brain. I do think that the physiological mechanisms are somewhat, in some ways,

01:33:56.160 mimicking some aspects of moderate intensity cardiovascular exercise. And that is how it is improving

01:34:02.440 cardiovascular health and also an aspect of that brain health, cardiorespiratory fitness that's been

01:34:07.620 shown. There's been not only like observational data, but there's been intervention studies looking

01:34:12.400 at endurance, getting someone on a stationary cycle, and then adding the sauna on top of that.

01:34:18.640 And VO2 max improvements were greater in individuals that are also doing the sauna right

01:34:23.200 after their training. So anything that improves cardiovascular health is going to improve brain health.

01:34:28.300 But there's another aspect to the story here, and this kind of dates back to like the origins of one

01:34:33.340 of my first biology experiments I did when I was actually a technician at the Salk Institute before I

01:34:39.740 went to graduate school. And that has to do with the heat shock protein response. And so we do know

01:34:46.160 that heat stress in the form of either hot baths or going into a hot sauna, infrared sauna,

01:34:53.500 a little different. You'd have to stay in there a long time to get a real heat shock response. But if

01:34:59.680 you're in like 163 degree Fahrenheit sauna for 30 minutes, we know that heat shock proteins increase

01:35:05.600 about 50% over baseline. And what would be the equivalent exposure in steam or water?

01:35:11.660 In the water, it's about 104 degrees for 20 minutes, shoulders down.

01:35:17.740 20 minutes?

01:35:18.300 Yeah, about 20 minutes.

01:35:19.720 And then presumably if you're in a hotter, dry sauna, less time is needed?

01:35:24.540 Presumably. We don't have that data. I'm just quoting the empirical data that we have.

01:35:28.980 Tell me more about the IR, because there are no questions I get asked more than, hey, are all the

01:35:34.940 benefits you're talking about, which all seem to come from studies in dry sauna, are they also applicable

01:35:39.680 to infrared saunas? To which the only data I can find is if you're using infrared, you actually have

01:35:47.260 to rely on the change in skin temperature. Whereas in dry sauna, we can look at time and temperature

01:35:52.240 and humidity. If I know the temperature of the sauna, the humidity of the sauna, and then the

01:35:55.580 duration that you're in there, I know how to measure the effect size. We can't do that in IR.

01:35:59.860 So we looked at some data that looked at basically thermal skin change. And I can't remember the

01:36:03.920 number, so I don't want to get it wrong. It was either five or eight degree increase in skin

01:36:08.360 temperature was necessary to produce similar benefits. Do you know about this?

01:36:12.440 Not that. I don't know specifically about that. But I do know most of the studies that have been

01:36:17.180 done comparing, and there have not been many, maybe three or four that I can think of, they have

01:36:23.580 compared a regular hot sauna to infrared sauna at the same amount of time. So in other words, the dose

01:36:30.800 is the same. Obviously, the temperature difference is pretty vast. Depending on the study, the hot sauna

01:36:35.460 could be 160 or it could be 175 or 180. And the infrared is like 140 or something like that. So a

01:36:42.560 lot of variation in terms of the temperature of the saunas. If you're looking at, in fact, there's like

01:36:47.920 one study, like the title of something like infrared saunas does not mimic cardiovascular effects of

01:36:53.900 exercise or something like that. And that's because the given dose, if you're just doing like 20 or 30

01:36:58.540 minutes, it's not going to be the same. Your heart rate doesn't go up as much. You don't feel as hot

01:37:04.680 because the temperature is not as hot. Now, you will sweat based on a different mechanism. But

01:37:09.340 as far as my take of the literature, it's pretty clear to me that infrared saunas, if you want it

01:37:16.900 to mimic the cardiovascular exercise response, you might have to double that. Duration. Yeah. So

01:37:23.420 rather than spending 20 minutes in 175 degree, 180 degree sauna, you're going to spend 40 minutes.

01:37:30.640 So you're giving up your time if that's the kind of sauna that you either have or enjoy.

01:37:37.200 Because if you do, and I've been in infrared saunas many times, if you stay in long enough,

01:37:42.220 you get that. You feel hot and you feel that heart rate going up just like you do when you're in a hot

01:37:47.720 sauna. It just takes a lot longer. Now, I know you've had Dr. Ashley Mason on your podcast. She's

01:37:52.800 been on my podcast as well. We collaborate. Isn't she awesome? She's awesome. Just love her.

01:37:57.200 She's awesome. And we collaborate on a variety of sauna studies. She wears a lot of hats.

01:38:02.500 And her data looking at, she's a psychologist by training and she looks at depression and she's

01:38:07.620 looking at depression as an endpoint in terms of these infrared saunas. And she's looking at core

01:38:13.000 body temperature increases. So people, their core body temperature is going up by like almost two

01:38:18.040 degrees. And in that case, I mean, she's got them in infrared sauna for like 85 minutes.

01:38:25.540 They're in there a long time and they are getting hot. She'll talk about it. She's got assistants that

01:38:30.320 are cooling them down on their head because it's a head out infrared sauna. It's like basically like

01:38:34.440 a bed. Anyways, that's the whole other area looking at the effects on mental health. And this actually

01:38:40.280 stems from her mentor, Dr. Charles Rezon, who I had on the podcast many years ago. He did this really

01:38:45.380 phenomenal pilot study looking at, it was a kind of funny, it's called hyperthermia. So like you're

01:38:51.360 inducing hyperthermia and there's like this funny chamber where it's increasing your core body

01:38:56.320 temperature, but Ashley's not using that anymore. She's established the heat bed as a safe way.

01:39:00.620 And what do you think is the role of the head being hot? So when I am in our sauna, which is a dry sauna,

01:39:06.640 and I'll run it pretty hot, at least 190.

01:39:09.260 Okay.

01:39:09.800 And again, part of it is I don't want to be in there for more than 20 minutes because time is tight.

01:39:13.460 Time is my most precious commodity. I'd rather do 190 to 200 for 20 minutes than go longer. But I

01:39:19.460 will tell you the most discomfort is in my head. Now, of course, part of that is I'm sitting on the

01:39:23.840 top bench. Temperature is hottest at the top. So I think my head is exposed to more heat than my

01:39:28.940 torso, just based on that difference. But is there harm or benefit or do we know anything that's

01:39:35.440 happening from any of these other metabolic parameters?

01:39:38.220 To answer that question, it'll take me in a whole other direction. Should I go there right now

01:39:41.500 or should I finish?

01:39:43.000 No, finish because I want to go there.

01:39:44.500 I'll finish and then go there. All right. So basically, the only point I was getting at was

01:39:47.480 the pioneering study where people with major depressive disorder were exposed to this device

01:39:52.040 where they're heating up their core body temperature by about two degrees. And they

01:39:55.600 had an antidepressant effect that lasted six months compared to a sham control, which was

01:39:59.320 also heating people up, not single treatment, single treatment. Now, Ashley has gone out and

01:40:03.780 she's done four to eight treatments, depending on the person, whether or not they've completed

01:40:08.380 the whole study. And she didn't have a sham control, but she's got just phenomenal.

01:40:12.560 How do you sham control that?

01:40:13.880 So what he did in his study was he had the same device that just got people a little bit

01:40:19.180 warm enough where they were thinking they were getting the active treatment, but it was

01:40:22.460 not.

01:40:22.860 Didn't hit the threshold.

01:40:24.020 Yeah. Raising their core body temperature by two degrees. It was a phenomenal study.

01:40:27.280 And this is, by the way, Peter, what got me interested in the sauna back in like 2008 when

01:40:31.920 I started doing it like every day. I lived across the street from OYMCA. I was going into

01:40:37.320 the sauna in the morning. It was freezing in Tennessee and I was going to the sauna in

01:40:40.100 the morning before I would go into the lab to do my experiments. I was going every single

01:40:44.020 morning and staying in a long time because I was like, go hard, go home kind of thing.

01:40:47.700 And I love the heat. And it was incredible the effect it was having on my mental health

01:40:51.980 and my ability to deal with stress and anxiety. So much that I was like, this is insane.

01:40:57.300 What's going on? Nothing has changed other than I'm going to the sauna every day before

01:41:00.760 I go and do all my failed experiments. And that's kind of what got me into the whole sauna

01:41:05.360 was actually the effect on my mental health. So it's kind of fun to go full circle and

01:41:09.780 team up with Ashley on some of this research as well. And she's amazing, by the way. And

01:41:14.260 she's got some new studies coming out in this whole field of sauna depression. I think just

01:41:18.580 she's opening the door. So that said, the effect on the head, if you think about like hot

01:41:25.080 tubs, jacuzzis, we're all sitting with our head out as well. We're in there and it's a

01:41:29.800 good question because I agree with you when I'm in a hot sauna and I'm also on the top

01:41:34.960 and it's the same deal. I want to get out in 20 minutes. If I stay in too long, I will

01:41:39.280 get a headache. I know my threshold now. I know the temperature and the duration and the

01:41:44.060 amount of water. I know all those variables.

01:41:46.340 Isn't it amazing how much water you can drink in a sauna?

01:41:49.040 I know.

01:41:50.160 I worry I'm going to get hyponatremia. I'm like, you got to slow this down.

01:41:53.440 So the interesting thing is, is that talking about dementia risk, I talked about heat shock

01:41:57.800 proteins and I kind of went off on this tangent, sorry, but the heat shock proteins, what they

01:42:02.520 do is they prevent proteins from misfolding and forming aggregates. And so obviously when

01:42:08.420 you're getting into a hot sauna, you are denaturing some proteins. And so your heat shock proteins

01:42:12.800 are a stress response that's activated to help with the proper folding of those proteins that

01:42:18.200 were kind of denatured somewhat from the heat that you were exposing yourself to. Well, it turns

01:42:21.920 out the heat shock proteins stay active for a long time. And so they end up having this effect

01:42:26.240 where you're now just improving the folding of proteins in general, even after you're out

01:42:31.140 of the hot sauna. So there's a lot of animal studies that have been done. I did a lot of

01:42:35.300 studies in worms many, many years ago where you can take amyloid beta 42, inject it into

01:42:41.040 a worm muscle tissue, and then activate heat shock proteins. And it prevents the aggregation

01:42:46.280 and it prevents the muscle paralysis that occurs in these worms. Animal studies have been done

01:42:51.520 looking at amyloid beta and heat shock proteins and Alzheimer's disease. Again, it's having a

01:42:56.840 protective effect. Now, is that the whole story? No, the cardiovascular effects are also important

01:43:02.440 for brain health, in my opinion. You know, the data coming out of Dr. Yari Lauchunin's lab showing

01:43:07.360 that dementia and Alzheimer's disease risk is 66% lower in people that are using the sauna four to seven

01:43:13.900 times per week versus just one time a week, of course. And that was at 179 degrees or greater

01:43:18.560 for 20 minutes or greater, right? Yeah, like 175 or 179 exactly for 20 minutes.

01:43:22.840 Now, here's where your question comes in, and that is like, what about the head? There was another

01:43:28.220 study out of Finland. It was not Yari's lab. It was another professor that I'm not aware of. But

01:43:32.820 this study looked at sauna use and dementia risk, and then it stratified the data based on temperature.

01:43:40.000 And it was protective again. People that are using the sauna, again, they're getting a protective

01:43:43.940 effect against dementia. But when people were going extreme, so if they're going above 200 degrees

01:43:49.820 Fahrenheit, and they're on average, it was like if they're getting to like 212. People do this,

01:43:54.460 by the way. This is like, you can go on Instagram and see it's not an uncommon thing. Their dementia

01:43:59.340 risk was actually increased with that temperature where it was really hot. My concern is the head

01:44:06.640 at that high of a temperature. I've started wearing one of those sauna hats. I don't know

01:44:12.620 why it works. Do you? It's not logical to me why it's helping, rather. I don't know. It does seem

01:44:17.140 to help. I mean, it shields probably some of the heat that you're being exposed to, right? Yeah,

01:44:21.660 I suppose. But the fact that that's a net benefit, because it's also got to be preventing you from

01:44:25.760 dissipating heat. Clearly, what it's preventing coming in is exceedingly, but it makes such a

01:44:30.760 difference. I've also dialed mine down a little bit. I used to be consistently going

01:44:35.060 to at least 200, and now I'm like, you know what? 185 to 190 is good enough. I do 180.

01:44:42.860 My wife is going to be very happy if we dial it down to 180. She seems more sensitive to the heat

01:44:46.940 than I am. I'm more sensitive to the heat than my husband is as well. I wonder if there's some

01:44:50.500 kind of sex thing where, yeah, it's definitely like I'm more sensitive to it. But this is important.

01:44:54.920 So you really think that we could even dial it to 180? Absolutely. And just totally get the same

01:44:59.100 benefit. I mean, the data is showing that. Yeah, yeah, I know. I just, you know me. More is better.

01:45:02.120 More is better. I'm not just you. It's the go hard, go home. But I do think we're talking about

01:45:06.200 a type of stress here, right? Yeah. And you have to get it hormetically correct.

01:45:09.380 Exactly. Exactly. I don't know that the 212, and I hope people that are out there doing the 212 are

01:45:14.980 listening to this because it's too hot. There's no need for it. There's no evidence you're getting

01:45:20.340 added benefit. And if anything, there's... Potential risk that you're getting.

01:45:23.180 Exactly. Potential risk downside. That's just one study.

01:45:25.900 Yeah, yeah.

01:45:26.500 But it's enough to make me go, hmm, there's no data showing we need that. So why are we doing that?

01:45:31.500 Rhonda, I know you got to go, but I want to end with just one question and topic, which is,

01:45:35.860 what year did you launch your podcast?

01:45:37.800 I launched it in...

01:45:39.880 14?

01:45:40.420 2014.

01:45:41.620 So here we are. We're 11 years in. You are the OG in this space. You have an incredible podcast.

01:45:49.840 Are you still enjoying it? And what are you most excited about?

01:45:53.500 I love doing the podcast. I don't do it every week like some people. I like to find the guests that I'm

01:46:00.280 really interested in learning from. What I love the most is I've always learned more from the

01:46:07.320 conversations I would have with my colleagues or professors than I would from reading a paper.

01:46:12.840 And now I get to do that for a living where I'm just having these superstars on my podcast and they

01:46:17.660 get to learn so much. I read their papers first, but I also learn so much from the conversation and

01:46:22.840 people get to benefit from it. I mean, it's so rewarding. So I get to scratch my own itch and

01:46:27.720 then I also get to help people. I just want to make sure that everybody listening kind of

01:46:31.680 understands your place in the podcast landscape, which is I've talked about one of my favorite

01:46:35.860 podcasts, probably my favorite podcast or one of my two favorite podcasts in the world is called

01:46:39.060 Acquired. So Acquired is a podcast about companies, great companies and what makes them great.

01:46:43.920 And the hosts of that, Ben Gilbert and David Rosenthal, they only put out one a month on average.

01:46:48.800 But the reason is the amount of work that they have to put into the preparation

01:46:51.840 is insane. And I've gotten to know Ben, especially, and Ben is putting at least 120

01:46:58.060 hours of preparation into each podcast. And therefore you can only do one a month and it

01:47:03.060 shows. So in many ways, I think of you as the acquired podcast version in our space, which

01:47:09.180 is just the breadth and the depth of what you're doing is awesome. It's such a treat. And it's

01:47:15.200 just, it's always quality over quantity. And yeah, I'm sure if you could put out one a week,

01:47:20.180 you would, but the reality is you wouldn't be able to put in the quality if you were trying

01:47:23.260 to bang one of these things out a week. Anyway, I'm glad to hear you're still loving it. And it's

01:47:27.320 hard to believe how fast time has gone. I remember being on your podcast in 2014. So that's insane.

01:47:33.000 You were like one of the first 10 guests.

01:47:35.320 I sort of knew what a podcast was because Tim Ferriss had had me on his, but it was like,

01:47:40.480 I didn't really understand what this was. I was like, I wonder, why does she want to talk to me?

01:47:44.140 Like, this seems kind of random, but look at how much it's evolved.

01:47:47.640 I know. Well, thank you for the kind words. And I feel the same

01:47:49.960 about your podcast. When I'm looking for information that I know I can trust, it's

01:47:54.860 always like, I'm like Peter. What's Peter? Peter is someone that I've always been able to

01:47:59.360 trust for being rigorous. Like you said, if something changes, then you change. I respect that.

01:48:05.880 Well, Rhonda, this has been super interesting. As is always the case, there were about 80% more

01:48:11.020 things we were supposed to talk about today, but I'm really glad that we got to the topics we talked

01:48:15.500 about. I think the protein question, the creatine question, and this nuance around temperature are

01:48:22.180 all things that matter to everybody. And in two of the three cases, I learned a lot. Obviously on

01:48:27.740 the protein side, it was more about you and I trying to set the record straight. This creatine

01:48:32.140 stuff is new. It's going to change what I do. And also you've already made a change to what I'm

01:48:36.300 going to do in the sauna. So thanks again. This was awesome.

01:48:38.640 Thanks Peter for having me on. I really appreciate it.

01:48:41.700 Thank you for listening to this week's episode of The Drive. Head over to peteratiamd.com

01:48:48.020 forward slash show notes. If you want to dig deeper into this episode, you can also find me on YouTube,

01:48:54.760 Instagram, and Twitter, all with the handle peteratiamd. You can also leave us review on Apple

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01:49:23.320 on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment.

01:49:29.140 Users should not disregard or delay in obtaining medical advice from any medical condition they have,

01:49:34.260 and they should seek the assistance of their healthcare professionals for any such conditions.

01:49:39.400 Finally, I take all conflicts of interest very seriously. For all of my disclosures and the

01:49:44.480 companies I invest in or advise, please visit peteratiamd.com forward slash about where I keep an up-to-date

01:49:52.440 and active list of all disclosures.

01:49:54.680 Thank you.

01:49:54.820 Thank you.

The Peter Attia Drive - October 20, 2025

#369 ‒ Rethinking protein needs for performance, muscle preservation, and longevity, and the mental and physical benefits of creatine supplementation and sauna use ｜ Rhonda Patrick, Ph.D.

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