Transcript of #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.

Hey, everyone. Welcome to be talking about how to get to the next episode of The Drive podcast. I'm your host, Peter Atia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to petereatea. Md. Com. Com/subscribe. My guest this week is Rhonda Patrick. Rhonda, returning for her third conversation on The Drive, is a scientist, health educator, and host of Found My Fitness podcast. Her work focuses on the intersection of nutrition, aging, and disease prevention, and she is widely recognized for bringing clarity to complex topics in health science.

This is part two of a deep dive on protein, but we expand into other topics like creatine supplementation and sauna use. In this episode, we discuss why the RDA for protein is too low and why a new minimum at least 50% more than the RDA is needed to avoid negative protein balance. The distinction between minimum optimal and high protein intake and how activity level and aging can affect requirements. Anabolic resistance, what it is, why inactivity drives it, and how resistance training restores sensitivity. The role of protein in preventing frailty and sarcopenia, and the quality of life implications in aging. Evidence on protein intake during pregnancy, adolescence, weight loss, and while using GLP-1 agonists. Addressing the concerns about MTOR, cancer risk, and reconciling protein intake with longevity research. The case for creatine, how it enhances strength and endurance performance, its overlooked benefits for cognition and brain health, and why dosing above 5 grams per day may be necessary. Practical guidelines on dosing, formulation, and the populations who may benefit most, for example, vegetarians, older adults, young athletes, older athletes. The science of sauna use, revisiting the mechanisms, especially as they pertain to cardiovascular adaptations and heat shock proteins, dementia risk and cardiovascular disease reduction, and best practices for temperature, duration, and frequency, how to weigh infrared versus traditional dry saunas, and why going hotter isn't always better.

I really enjoyed this discussion with Rhonda, and I'm truly hopeful that this is the last time I need to do a podcast in a very long time that addresses some of the controversy surrounding protein intake. So without further delay, please enjoy my conversation with Rhonda Patrick.

Rhonda, so great to see I didn't realize until a few minutes ago that the last time we spoke, it was virtual. Yeah, good to see you. We go back a long way.

You're still in our same former neighborhood in San Diego.

I know. I'm thinking that you found the same feeling here in Austin.

Yeah, we did. All right. Well, there's a lot we want to chat about today, and I'm a little hesitant to say this, but I do feel like reluctantly we need to have one more discussion about a particular macronutrient that seems to get a lot of attention lately. I don't necessarily want to talk about this because I think it's especially interesting or even to which there's some new study that we need to shed light on. But it does seem to remain somewhat surrounded in some controversy, which I will refrain from publicly speculating on why said controversy exists, although privately, I'm very happy to speculate on all the reasons for it. With that said, let's talk about protein.

Let's do it. I do think it's an important topic. You and I have probably We talked to all the world's experts on protein, and we were chatting a moment ago about this recommended daily allowance for protein, the so-called RDA. Really what it should be called is the minimal daily allowance. Recommend it almost sounds like optimal in a way. I think people confuse that with the optimal amount of protein, right? It's tricky. I think that's an important place to start because of that reason where this amount, which is 0. 8 grams per kilogram body weight per day, is the RDA for protein. I know that you've probably had countless experts on talking about this I've had experts on talking about the stew Phillips being one. There's so many different publications. People can start off by reading one of them here by Stu Phillips. Perspective: Protein requirements and optimal intakes in aging. Are we ready to recommend more than the recommended daily allowance. There's several of these out there. This is just one. Essentially, if you have the time and the willingness to go into the scientific literature and actually read something for yourself or listen to The Drive or listen to my podcast and the actual experts talking about it, what you will hear or what you will learn is that a lot of the studies that were done to determine this RDA were flawed.

They were called nitrogen Balanced Studies. For many reasons, they're flawed. I don't want to get into all the technical reasons, but for one, what they are doing is measuring the amount of nitrogen that is excreted in urine after you are metabolizing protein. Some of the flaws that I would say the most important here are that different types of foods that have protein in them have different nitrogen to protein ratios. They're collecting urine, in which the case is that it's an incomplete collection. When you pee in one of those cups, you don't get all the urine. It's incomplete collection.

We lose We lose the nitrogen through other means. Exactly. That is not just urine.

Yes, exactly. We lose the nitrogen through other means. Essentially, the signal to noise ratio is pretty low. Ultimately, what countless experts have now agreed upon is that the protein for the RDA has been underestimated because of those reasons. There have been new studies that have been done. These have been more stable isotope studies. The major isotope that's used is the L13 carbon labeling phenalalanine, in which case these studies take a small cohort of people, give them a known amount of protein with that isotope tracer, and then that tracer is oxidized when it's metabolized, and that's measured through breath, the oxidation of phenalalanine. Now you're getting a quantification that's much more accurate in terms of your protein steady-state and turnover. The whole point here is that you're trying to figure out the minimal amount of protein you need to take in every day to make sure that you're not a negative protein balance. Why is that important? Well, that's important because we don't store amino acids. We don't store amino acids like we store fatty acids as triglycerides or we store glucose as glycogen. The major source of our amino acid storage tank, so to speak, is our muscle, skeletal muscle tissue.

You don't want to be pulling from that skeletal muscle tissue to get amino acids every day. Why do we need amino acids every day? Because everything in our body requires proteins. Proteins are doing all the work on our body, and proteins are made up of amino acids. We have to be giving ourselves an intake, daily intake of amino acids to make sure we're able to do all those functions.

I just want to state that again, because I do think there's a very important and fundamental point here that is glossed over When we talk about it, because we take it for granted. If we studied biochemistry, and anybody who's studied biochemistry will know this, but we can store fat in unlimited quantities. If you deprive a person of fat calories for a period of time, they have a long reservoir that they can dig into. Not indefinitely, but they can. We can store carbohydrates. Now, we can't store them quite as much because we only have so much glycaogen we can store in the muscle and in the liver. But when we break down fat, we keep making the substrate to actually make glucose, so we get into a nice little rhythm. But to your point, the only place that an amino acid sits in residence in our body is in the muscle. Therefore, if we even When we can get near the edge where we are not getting sufficient intake of amino acids, we don't have a buffer. We don't have a rainy day fund that we can dip into. We immediately start to catabolize or break down muscle.

Now, I don't think we have to make the case that that's a bad idea, but for the sake of completeness, we should state there is not really a single scenario I can think of that is clinically relevant, where it would be desirable to give up muscle mass. Maybe if you're Mr. Olympia, you can sacrifice muscle mass. But for you and me, and I think everybody listening to us, giving up muscle mass because we are falling short on our protein intake would be a strategic error and an enforced error.

Exactly. For short-term and long-term health. I think that's pretty clear. That's where this RDA not being enough is a very important point. Let me go back to this isotope tracer studies. Multiple studies, multiple studies, as you know, have shown- We'll link to these in the show notes, by the way, just so that people can go and actually look at the papers as opposed to reading about it on social media. Sounds good. Multiple of these papers have shown that really going up to more like 1. 2 grams per kilogram body weight per day is what is needed to prevent people, us, adults, from being in this negative protein balance. That's quite a bit more than the 0. 8 grams. It's 50% more. It's 50% more. Most of the studies done, isotope tracer studies They're between 30 to 50% more. That's really important because if we look at the actual protein intakes of adults, these are nutritional surveys that are done. Of course, they're all flawed. We can talk about it. We all know the flaws of questionnaires, but let's just talk When we talk about what we think people are actually taking in. Adults are mostly taking in, all adults are taking in about 0.

9 grams per kilogram body weight per day of protein. So pretty close to what that RDA is, not what it should be. Old Those are adults. If we look at the gender, male versus female, males are taking in about 0. 9 grams per kilo on body weight. Females are taking in 0. 8. They're really just hitting that, what we call RDA, which now we have established is not enough. The RDA is not enough to basically be in a net protein balance. That's really important. That's essentially telling us that most adults are walking around without being in steady-state protein balance.

Here's an interesting question, Rhonda. We know the rates at which muscle mass, skeletal mass, are declining by decade in an aging population. Is there any way we can estimate... I'm guessing the answer is no, but on the off chance, you would know. Is there any way we can estimate what % of that decay is simply being driven by insufficient amino acid consumption versus other factors. Other factors would be anabolic resistance associated with aging. Other factors would be anabolic resistance associated with sedentary behavior. Other factors would be lack of sufficient resistance training. There are many factors that explain clearly the fact that as a person goes from 50 to 60 to 70, on average, they're losing muscle mass. But it would be interesting to consider how much of that is explained by the fact that they are also barely skirting the minimum amount of nitrogen that they need, and in many cases, falling below it.

Right. To answer your question, I don't know that there's a direct way to do that, but I do know that there are studies that have shown that when older adults, so older adults that are really more susceptible to the things that you were saying, like anabolic resistance, where your muscle tissue is not as sensitive to amino acids, mostly because of physical inactivity, which increases with age. But when older adults take in 1. 2 grams per kilogram body weight per day of protein, it nearly eliminates some of the age-related muscle loss that happens. I think that is some evidence to support what you were saying in that if you just increase your protein intake, Take by 50% to this minimum, what the RDA should be, 1. 2 grams per kilogram bodyweight per day. I think that's pretty much what most all the experts agree. It's time to change that RDA to that number, the minimal amount that you need per day. If elder adults just do that, they're actually preventing a lot of the age-related loss in muscle that occurs. We also know that older women, if they take in that amount of 1. 2 grams per kilogram bodyweight per day, they're 30% less likely to have frailty in old age, which is also very important.

I think that's pretty good evidence that it's clear that just increasing your protein intake by 50% is really important for aging, for our muscle health, and also is getting us out of that net negative state that we're in.

Step one is we should move the floor from 0. 8 to 1. 2. Yes.

I think the floor being the minimal amount of protein that we need to take in per day. This is not optimal. We're going to get into optimal. This is just the new RDA. As you mentioned, so you hit on this anabolic resistance. I think that's also a really, really important point because it does compound with the fact that we're already not getting enough protein to be in a positive state of protein balance. Then you compound that with anabolic resistance. Now, anabolic resistance is when your muscle tissue becomes less sensitive to amino acids, and so you're not making as much muscle protein synthesis isn't occurring as much as it does when you're younger. I think it's pretty consensus now that a lot of anabolic resistance is not necessarily aging, the aging process per se, so much as- Inactivity.

Inactivity. Yeah. The experiment that Luc von Luhn shared when he was on the podcast, I think, was a very elegant way to do this, which is they took young subjects. I don't remember if they were in their 20s, but it was thereabouts, maybe in their 30s. So very young subjects. And they put a cast on one leg, no cast on the other, and they left them in this state for a period of time. Again, the details have now completely escaped me, but the point has not escaped me, which is after whatever period of time the individuals were casted on one leg, not casted on the other, let's just say it was two weeks, four weeks, something to that effect, they removed the cast. Of course, while the person was casted, the casted leg did nothing. The other leg continued to go through exercises. They were doing not just single leg, leg extensions, leg curves, things like that. They then ran the stable isotope experiment in these individuals and looked at muscle protein synthesis rates. And lo and behold, the leg that was uncasted, perfectly normal, the other one, significant anabolic resistance. So to me, that's the clearest demonstration that inactivity is the main culprit.

There's probably an all things equal age-related component as well. But I suspect that inactivity is playing a larger role than aging per se.

I totally agreed. Yeah, I think there's also another study that was done in older adults.

Can we explain what anabolic resistance is? I think it's worth people understanding why this idea matters. Yeah.

Anabolic resistance. When we eat protein, we're breaking amino acids, and the primary amino acid that is anabolic is leucine. Gleucine are getting into the muscle tissue, and that is instigating. It's a signal to increase muscle protein synthesis. You're making more protein in your muscle, and that in turn increases muscle hypertrophy. The other major signal to do that is mechanical force. That would be the resistance training working of the muscles. As we get older, our muscles do become less sensitive to those amino acids, the leucine transporter being one of the major ways, but I think there's others as well. What happens is that for the same amount protein dose, and this study has been done, and if you compare younger adults and older adults, 65 years, age and older, you give them the same exact protein dose. The younger adults have twice as much muscle protein synthesis. For the older adults to get the same amount of muscle protein synthesis, they had to double their amount of protein to get the same amount of muscle protein synthesis as the younger adults. That's a lot. Double that amount of protein. That's because, again, it's just your muscle tissue is not as sensitive to the amino acids.

To get more of them in, you have to increase your intake of the protein. Now, to your point about physical activity being the major driver here I think that's 100% agree. I think it's totally true, and there's so much evidence out there to prove that. Luc Van Luhne's study being one, but also older adults that do engage in resistance training have the same anabolic response to the same amount of protein as younger adults.

In other words- The activity makes up for it. It does.

As you're aging, if you're a 65, 70-year-old male listening to this episode and you're engaging resistance training, you're likely not experiencing much anabolic resistance, maybe a little, but not much. You don't necessarily have to experience it if you are physically active in training. That's really the bottom line here. That's the most important thing. If there's a public health message in this episode, it really is you should be training.

Yeah. And think about the impact that physical training has on insulin resistance as well. Completely different mechanism of action, probably ties in more to fatty acid accumulation within muscles and all sorts of other things that lead to it. But again, the most effective remedy is physical activity. It's been demonstrated so conclusively that actually nobody really talks about it. It's just taken for granted.

It's a good point. So the anabolic resistance, if we're talking about general population, again, we're going back to these surveys that are done looking at how physically active are people because those numbers are out there. We know that, generally speaking, adults, including young and old adults, about 32% of them engage in resistance training. How much? 32, both young and old. If you just look at older adults, it's 22% of the population. Essentially, most older adults, most people, are not engaging resistance training. They're not doing resistance training. Physical activity mirrors a little bit those numbers. But I I think the bottom line here is that putting in the effort, it's harder for people. Putting in the effort is harder. It's easier for them to just increase putting something in their mouth. That's why pills are so popular. People always gravitate towards the easier thing to do, Which is I'm going to eat something. I'm going to put something in my mouth, versus putting in the effort. It's unfortunate, but it's a reality. I think that even just going back to this RDA being too low, it's just so important. It's so important because people are out there thinking they're getting enough protein.

Older adults, younger adults. It's really more important with older adults. You have a little bit of wiggle room when you're younger. Then on top of that, first of all, it's not enough protein. Then this anabolic resistance is setting in, and most people are not being active. They're not engaging in resistance training. There's all these compounding factors that's really just digging into their muscle. It's taking away this insidious taking away each year, each year. Then the next thing you know, you're frail, you have sarcopenia.

My patients are obviously indoctrinated into this, but I'm a bit surprised that there aren't more people that talk about this. You do a lot, but the medical system doesn't seem to talk enough about frailty and sarcopenia. I worry that even when I wrote Outlive, I didn't do enough of a job emphasizing it. I mean, I certainly talked about it, but when I talked about Four Horsemen, I talked about cardiovascular and cerebrovascular disease, cancer, neurodegenerative and dementing diseases, and metabolic disease. Because, of course, those are the things that are the main assault on your lifespan. And relative to those, frailty is not as big an assault on lifespan. It is, as you know, the risk of falls are enormous and the mortality is very high once you're north of 75. But relative to those four, I had to pick four horsemen. I didn't want to go with five. But when you think about quality of life, which most people care about at least as much, if not slightly more than length of life, I think frailty just wins the day. I think along with cognitive health and minimizing too much cognitive decline, frailty is the thing that seems to determine the quality of your final decade on this Earth.

Here we have lots of great tools both in terms of training and nutrition that can offset that. And yet it is surprising that despite the fact that most people have witnessed it, that's the part that's amazing to me. It's not like the people who are suffering from frailty and sarcopenia are out of sight because they're our parents and our grandparents. We've watched it. We've been to the movie over and over and over again. We see how it goes. And yet somehow we either don't think it's going to happen to us or it somehow still seems abstract because it's so many years off. What's your take on this overall challenge?

For one, I completely agree with the frailty risk being as important, if not more. And witnessing it with family members, what I think it is, is that it's this incremental thing where something happens. Maybe there's a fall or maybe there's just a surgery, a planned surgery or a hip replacement or a knee replacement. If your parents or your grandparents are inactive for many weeks, and they lose a lot of muscle mass. So this happens. If this is a younger person, it's much easier to gain back that muscle mass. It's not the same with an older adult. It's just not the same. Even if you're engaging in resistance training after, you're not going to get the same amount of muscle mass back as you've lost. And these sorts of events happen in periods of time. There's a planned surgery, then there's a fall, and maybe there's another surgery, or maybe there's COVID, or the flu, whatever it is. They They keep hitting, and you reach this what's called disability threshold, where all of a sudden, your parents, they just can't walk much at all anymore. It's all of a sudden, it's like, When did this happen?

Well, the evidence was mounting over the last five years when They had these points of inactivity that were occurring. I think people just don't follow the timeline where it's like they see what's leading up to it before this catabolic crisis occurs, where then they reach this point now where they've just lost so muscle mass from these several events that have occurred where they're just not mobile. Then, of course, anabolic resistance is kicking in even more and more and more, and everything is just compounding. I don't think they've observed the timeline and said, Oh, A plus B plus C is getting me to this point. I think that's what happens, whereas with Alzheimer's disease, I don't know, it's just this disease everyone knows about, and it's like, Yeah, this one thing causes the problem.

Yeah. Luke Van Luhne made a really good point when we spoke, which was when we draw the curve for how people lose strength and how people lose muscle mass, we draw it in a curved smooth line, which gives us the incorrect impression that this is a gradual and imperceptible changing physiologic process. But he goes, That's because it's averaging everything. If you zoom in and look at it at the individual level, it looks like this, exactly as you described, discrete periods of loss from which there is no recovery recovery, because at the later points in life, it becomes very difficult to make those recoveries. All of this, of course, points back to where we're going today, which is when you are young, and young is 40, 50, even 60, you have to build up as much physiologic headroom as possible. You have to prepare for the rainy day because the rainy day is coming. It's not a question of if, it's simply a question of when and exactly in what fashion it will be delivered. But you must prepare for this. You must steal your sofa what is coming, and you must build up as much muscle mass and strength and cardiovascular fitness as you can muster, because the longer you can ride it out, the better you're going to be.

The cliff is coming for sure. I mean, it's like your retirement fund. You have to put money in because one day you will retire. If you don't put any money in that fund, you're going to be screwed. With the muscle mass, you're right. You have to bank as much as you can while you're We haven't even talked about optimal. We've just talked about-Not going backwards, right?

Yeah.

We've talked about not going backwards, which is what most people are doing because this RDA is too low for one. I think that's the big problem. But optimal is a whole other story. That's, again, where it's hard to wrap your head around why there's controversy around this. Although coming from the field of aging, I do have somewhat of a... I think there's been a little bit of a nuanced approach to looking at protein affects the way we age. I think some of that data has biased researchers and people to think that protein is bad. I think some of it's coming from that evidence, which we can talk about.

That's an interesting point.

Again, aside from that, it's really hard to understand why someone would be so opposed to increasing protein intake when there's really just no evidence that it's harmful, at least in healthy adults.

Yeah. I mean, I'd like to talk about harm down the line as we get further up the chain, because we've now just... I like the way we're talking We're talking about this, where we're going from 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. And as you continue this journey, let's say you look at the data, of which there are some studies, looking at three grams per kilogram. Per day, which I think anybody who looks at the data would argue, you're not really getting a benefit at three grams per day that you aren't getting at two grams per day. The curve is saturating. You're hitting an asymptote of muscle protein synthesis at that point. So There may be other reasons a person would choose to consume that much protein, satiety, and things of that nature. But from a purely anabolic reason, under normal conditions, let's leave bodybuilding out of it, you hit the saturation curve, but can't seem to find the evidence that is causing any harm. This is experimental evidence, even epidemiologic evidence, just no evidence. But that said, let's not get ahead of ourselves.

Let's go back to, we've established a new floor. There is nobody that should be consuming less than 1. 2 grams of protein per kilogram per day. What happens as we start to increase that from 1. 2 to 1. 6?

This, again, is where I turn to the experts like Stu Phillips. In fact, he did a really great meta-analysis, looking at about 49 different studies in adults that were undergoing controlled trials, resistance training alone or resistance training plus supplemental protein. The supplemental protein went up to 1. 6. Well, actually, it went up above that. But But what was really found in that study was that even going from 1. 2 grams per kilogram bodyweight per day, obviously, to 1. 6 grams per kilogram bodyweight, people gained about 27% more lean body mass and 10% more muscle strength compared to just training alone. Same training, just adding the protein. That's pretty big.

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

In the strength side. The protein itself, but if you think about it in a way, we're talking about supply and demand. Now we're talking about more optimal, a little more optimal. We're talking about people that are training. That's number one. You need to be training. If we're talking about optimal protein intake, you need to be training. Then what's happening when you're training is you're breaking down muscle. You need protein to support the repair of that muscle and the rebuilding of it. That makes sense in a way. But yeah, I was surprised by the strength as well. Really, once you went above 1. 6 grams, there were still increases in muscle protein synthesis.

Yeah, but the curve is slowing down.

I like the analogy that Steve Phillips uses. He says, If you have a wet washcloth, you squeeze it to get all the water out, most of that water is coming out at 1. 6 grams per kilogram body weight. But you can keep squeezing a little and you're still getting some water out. It's just marginal. It's like most people don't care about that difference. Some people do. Now, let's say you're someone that's obsessed with banking muscle mass. You're going to care about that. Let's say you're a high-level athlete, definitely going to have to go above 1. 6. That's when you get into the more 2, 2. 2 grams per kilo on body weight. So people that are doing a high level of training, whether that's endurance or strength training, resistance training, because endurance athletes, you are battling being catabolic. I think the evidence for more optimal, you're talking about 1. 6 grams per kilogram bodyweight, you can get marginal benefits above that up to 2, 2. 2 grams per kilogram bodyweight. But Again, that's people that are really training.

To me, there's an analogy here with APO-B and cardiovascular disease. If you look at the three bodies of evidence, if you look at all of the epidemiologic data, if you look at all of the clinical trial data, and if you look at all of the Mendelian randomization data, and you plot every single one of them on a graph, and there's a beautiful graph, which we'll include in the show notes, that does this. On the X axis, and it's done in LDLC. Again, LDL-C, APO-B, easy to view them together. On the On the X axis, you have LDL-C going down. So from 160, 140, 120, 100, 80, 60. So descending LDLC, and on the Y axis, you have mortality, cardiovascular mortality. So not surprisingly, all of these point down. As LDLC goes lower, cardiovascular mortality goes lower. What's interesting, though, is you can see that there are different points in the curve at which it starts to matter more. At some point, it flattens out. You don't get as much benefit from reduction. We could use the same argument of, Well, what is optimal? Because we're doing the reverse here. Here, lower is better as opposed to going up on protein.

But Peter Libby has done an analysis that has demonstrated that you will continue to see a meaningful reduction in cardiovascular disease as APO-B heads towards 30 milligrams per deciliter. 30 milligrams per deciliter is really low by most people's standards. For context, 60 milligrams per deciliter is about the fifth percentile at the population level. 30 milligrams per deciliter is about what a child is. We're born with relatively low levels of APO-B, and as we age, they just keep going up and up and up, which, of course, is one of the things that's driving cardiovascular disease is this rise in APO-B. The question then becomes, how low do you need to go? Should everybody be walking around at 30 milligrams per deciliter? Is that the solution to eliminating ASCVD? The answer is probably not. It probably depends on your previous exposure, though. If I have a patient who's already had two stents placed and has a significant burden of disease, you bet your bottom line there at 30 milligrams per deciliter of APO-B, even if we have to put three drugs on them to make sure that's the case, because their burden of disease and their lifetime exposure to APO-B has been so high.

But if I have an individual who's 40 years old, who has perfectly pristine coronary arteries and is walking around with an APO B of 60 milligrams per deciliter, I don't think you need to do a thing. I think they're just fine. And again, it's the inability, I think for people to understand that level of nuance and understanding when it's worth the second squeeze versus when just the sloppy squeeze is good enough. It's very frustrating for a person like me who craves nuance.

Agreed. I love that analogy. I think it's perfect because I do think most people that are training probably are getting a great amount of benefit from 1. 6 grams per kilogram bodyweight. But that doesn't mean you can't go above that and still get a little more benefit. Certainly, when you start to get into that energy deficit phase as well. We were talking about elite endurance athletes. That's one way to be in an energy deficit. But there's also people that are actively trying to lose fat, gain muscle. If you want to lose fat and gain muscle at the same time, you're going to have to take in a lot of protein.

Yeah. So that's another very important point. Another point I want to make is you're still dealing with an asymmetric target. We tell our patients to be closer to two. Now, I know that's just going to get a whole bunch of people on the anti-protein train just losing their mind. I can just see the phosphorylation going off right now as they're watching this clip. How is this guy so irresponsible to tell his patients to eat two grams of protein per kilogram of bodyweight? Didn't he just hear what Rhonda said, 1. 6 is good enough for most people? Well, my patients, unfortunately, don't live in labs. Unfortunately, Rhonda, my patients live in this place. It's called the real world. In the real world, you can't always hit your targets. Some days you do, some days you don't. Some days you're traveling, some days you're not. Some days you can figure it out, some days you can't. If I'm telling 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 1. 5, another day they're at 1. 9. On average, they might hit 1. 6. But how many days were they below versus how many days were they above?

Let's just say it's an equal split. But we've just established the shape of this curve is like this. That means every day you're below, the downside is much greater than the upside of being above. In other words, all the days you're above are not making up for all the days you're below. What I'd really like to do is shift the range so that your low day is 1. 6, and your high day is maybe 2. 2. And then guess what? You don't have days where you are ever, ever amino acid restricted. This is the difference between people who take care of people in the real world and bozos who write on Substack who don't know the first thing about clinical medicine when it comes to managing athletes and people who have to fend for themselves every day with every meal. This is why I'm so tired of talking about this, but I feel we need to talk about it. If you're sitting there listening to this and you're confused and you're asking, Oh, my God, should I be eating two grams per day? Yeah, more or less. That way, if you fall short at 1.

6, you can confident that you're okay. But if you're aiming at 1. 6 and you have a bad day, and you will, when you hit 1. 2, you might be taking a step backwards and you won't make up for it the next day.

I can just tell you from personal experience, it's actually smarter to aim higher because I'm constantly not meeting the 1. 6.

I am not. This is the thing. People look at me like I'm a protein eating machine, which, first of all, I'm not. But secondly, I have a hard time hitting my goals, too. I'm busy. I miss meals. Sometimes we just have a low protein meal. For whatever reason, my kids want to have pasta for dinner. We literally have pasta and sauce. There's no freaking protein in this anyway. It's very difficult if you don't have a chef preparing your every meal, and I never have a chef preparing any of my meals unless I'm out at a restaurant, to hit these targets every day.

Right. I was thinking about this because we mentioned the 1. 2 being the minimum buy-in. The 1. 6 grams per kilogram bottle isn't necessarily just for people training a little bit. It's also older adults that are not training because we talked about the anabolic resistance, them needing twice as much protein as well. What you're talking about here is going up to two so that you can really have an average, at least of 1. 6. You're getting that average.

I never want to fall below that. That's really the point is I know I'm training every single day. Now, am I training like a madman? No. But seven days a week, I'm either doing some form of cardio or something in the gym. It's just I know that I'm going to take steps backwards if I'm below 1. 6. So I'm going to overshoot so that my down day is 1. 6. If my up day is 2. 5 once in a while, who cares? Because that gets to the next point. Show me the data. Show me the data that eating 2. 5 grams of protein per kilogram per day is even remotely harmful. I'm still waiting for it. I'm still waiting for the data. David Allison wrote a piece on LinkedIn recently where it was basically a call to anyone. Just show me the data that meet these criteria, human clinical trials trial of this duration, nothing but crickets.

Yeah. I haven't seen any human data either, for sure.

The most negative data I saw recently was a study that looked at total parenteral nutrition in ICU patients, where the question was, Hey, should we be ramming high amounts of protein in these people? The most negative thing you could say is it had no benefit. That's interesting. Yeah. Maybe we shouldn't be ramming high protein, total parenteral nutrition into the central veins of critically ill ICU patients. But it didn't harm them. If anybody's going to be harmed, I would think it's the people that are in renal failure.

Yeah, exactly. I haven't seen that data either.

We haven't spoken specifically about pregnancy or adolescence. What do we know about protein requirements? Because there are clearly women listening to us right now who are pregnant or who will be pregnant. I don't think there are any adolescents listening to us, but I bet there are parents of adolescents. What guidance would we want to give these folks?

It goes up with pregnancy and also adolescents.

Are there formal recommendations?

I don't remember. Again, it's all about going a little bit above what's the RDA, and we've already established that's not enough. Honestly, I think if people are listening to this episode, just knowing that 0. 8 grams per kilogram bodyweight per day is just not enough.

If we accomplish nothing else, that's the single most important take home message here.

I really think it is because everyone looks at those guidelines.

Yeah, it's really funny. The other day, I was eating something, and I forget how much protein it had in it, but it had % of daily requirement, but it was obviously baked to a very low number because I remember my son was looking at it with me and he goes, I forgot what the number was. Is that really 40% of your daily protein requirement? And it was relatively... And I said, No. But I just didn't have the energy to explain the RDA to him. So I was like, No, this is just wrong. You can ignore this.

Growing is also an important time for protein, right? Because these amino acids and the essential amino acids are activating IGF1 growth hormone, and that's really important for growth. I know there were studies done in infants and toddlers that were given egg versus milk versus some vegan protein, and it was clear that the egg was the winner here. Giving protein with more essential amino acids was important for growing taller. That's always something that I, as a mom, think about. I'm always trying to get protein in my son. Plus, the kids are more active. Kids are more physically active. They're doing sports and things like that, adolescents. It's really important to get the protein requirements. I haven't dug into all the nuance of that data. The way I look 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 kilogram for an adolescent who's pretty close in body size to an adult, generally speaking, they start growing pretty tall.

I would think for kids, it should be at least the 1. 2 to 1. 6. Just look at the activity level of my kids, they make me look sedentary. Anything else we want to say on the topic of protein to help with some of the confusion that is out there. I think we should talk a little bit about some of the misconstrued understanding of mechanisms of action around MTOR, cancer, and stuff like that.

I would say the other thing would be the calorie restriction, people doing intermittent fasting, people doing anything if they're wanting to beat body recomposition, the gaining of muscle and losing fat. I think that is a very specific group of a population of people where the high protein intake is critical because if you're in a caloric deficit, you really are battling your body, pulling from your muscle reserve. If you're resistance training, that helps somewhat, but you're certainly not going to gain muscle. We just talked about wanting to bank as much muscle as possible as we're younger while we can because we need that reserve because we're going to start pulling from it eventually. I think that that's where you start to get really high numbers, 2. 2, even higher. You can find studies out there. It's like three grams per kilogram per body weight. Going above the 1. 6 in this scenario seems to be key as well. You're getting up to that 2. 2 grams per kilogram bodyweight per day because it does give you a little bit more edge over gaining muscle, muscle protein synthesis in combination with resistance training As well as it's like you mentioned, it's satiating, a little bit thermogenic.

I don't know that that's the big mechanism here, but I think the big mechanism here is just you're really wanting to prevent this catabolism. I think that's just another important point because there are a lot of people that do intermittent fasting, time-stripted eating. They're trying to do body recomp, gain muscle, lose fat. I think a lot of people are interested in that.

There was one period in my life when over the course of a year, I made a very dedicated goal to lose body weight and gain muscle. I wanted to see, could this be done? And it did require quite a bit of intermittent fasting or time-restricted eating, I suppose, to be more accurate. But the amount of attention I had to pay to protein intake was pretty incredible. And what I did that seems counterintuitive because I wasn't intermittent fasting because I believed that a fasted state was producing some benefit. There are some people who think that, well, if I don't eat breakfast, I'm kicking off some autophagy or something. No, no, it was purely a caloric restriction employ. So my fasting window did not prevent consuming liquid protein. In other words, if I wasn't eating breakfast or lunch, which I wasn't, I was only having a meal a day, which was dinner, but I would still consume protein shakes outside of those windows. Otherwise, I could never hit the protein target. I was in a caloric deficit, but an amino acid excess. And again, you can actually do that with liquid protein pretty easily because basically all you're getting is getting relatively few calories because you're just consuming whey protein.

Did you have any GI problems consuming so many shakes?

No, but I did a lot of experimentation. So ultimately, I settled on a brand. I'm blanking on the name of it now. I have no affiliation with these guys, and I'm blanking on their name. Ascent, maybe. Does that ring a bell? I really like them. Again, I'll give them a shout out because, one, it was the only protein I found I could mix directly in water and not have it be lumpy. I didn't even need a blender. This sounds silly, but the hassle of me having to wash a blender twice a day was sometimes an impediment to not making a shake. Just to be able to put the scoop or two scoops I would usually put into a glass with water and mix it with a fork and actually drink it and have it be totally fine and not lumpy. I don't know how they do this, but it was amazing. It actually tasted fine. I don't like sweet drinks that much, but it was not too sweet, and absolutely no GI issues at all. Whereas sometimes the pure egg proteins, I didn't like the feeling on my gut. For whatever reason, that worked for me.

But to your point, it's another level of challenge if you're trying to recomp in that way.

Or people on GLP-1, right? Receptor agonist, right? I don't know how difficult it is to eat a meal versus take a protein shake. You're satiated pretty much all the time. You don't have a real appetite, but also, digestion is slow. If you're consuming more protein, I don't know how that all affects.

We've seen in our patients, I get asked this all the time, I would say 15% to 20% of our patients are on Trizeptide. Unlike five years ago when we started using semaglutide in patients and were just watching muscle fall off these people, and frankly, my point of view five years ago was, I don't know about these drugs. I think there's some benefit in some people, but I think there's a lot of downside. I today think that virtually anybody can use these drugs safely. By safely, I don't just mean in the obvious sense of the word. I mean safely for long term muscle health as well. But it requires a ton of deliberate attention. I'm glad you brought it up. This is exactly the group of people who you want to be using easy to digest protein sources. If you're on Tersepatide, you don't really want a steak. You don't really want to have a big chicken breast. You might not want to even have an omelet. But if we have to make sure you're hitting that 1. 6, you might be doing a bunch of liquid shakes. Yeah, we can sit here and poopoo processed food and say, How disgusting is it that people have to resort to eating shakes?

Okay, fine. But if the alternative is they're not getting enough protein and they're on a drug that is making them anorexic, we also know the downside of that.

Well, the answer is clear, right? You don't want to be losing muscle mass, for sure.

My point is, we do Dexa before and after. We're not seeing the type of muscle loss we saw with our V1 approach to this.

What dose? Are they on a higher dose?

No. I think for... Trisepatide starts at 2. 5. Some people are getting enough benefit there. The other thing that I think our approach has been is that slow and steady wins the race. We've seen anecdotally some data. I've heard from others, and we've seen it as well, that yo-yoing on and off these drugs is probably a bad idea. I always tell patient, Look, I'd probably rather you were on 2. 5 milligrams until there was a new drug that we felt was even better, then you're on 10 milligrams, you lose a ton of weight, you come off, you gain, you go back on, you lose. The idea of being on a saw is probably a bad idea. I think the data suggests you're getting most of the value by about 10 milligrams. So once you go to 12. 5 and 15, which are the two highest doses, you're still getting a benefit. But it's like most drugs, you're getting most of the benefit at the lowest dose. So 5 to 7. 5 milligrams of trizepatide is probably where you're getting the majority of the benefit. I'd much rather a patient be slow and steady on it as opposed to try to go for maximum and rapid weight loss.

What do you think about some of that data on heart issues or bone loss? Does that concern you at all?

Sure. I think it all does. I think all of this stuff has to be paid attention to. I think the question, again, comes back to how much of that is occurring due to training. How much of that is happening due to the loss loss of amino acid intake and the loss of training.

Or the neuropsychiatric, that's another one, the I's. What I'm interested in is we have these GLP-1 receptors on so many different tissues. Systemically, is it beneficial Was it not beneficial? I don't know that we really know. We have data where there's obviously positive effects. You see reduced Alzheimer's disease incidents with people taking these GLP-1 receptor agonists. But how much is that due to weight loss?

We've looked into this a lot because it's funny. We did a podcast on this somewhat recently where I went through this particular question, which is, will GLP-1 receptor agonist ultimately prove to be geo-protective? I came up with a very obscure way to define that, which is, in independent of weight loss. Because obviously, at the macro level, they're going to be geo-protective, because if you apply them to people with type 2 diabetes and significant obesity, and you correct the metabolic dysfunction, you're going to live longer. So by that regard, it's a geo-protective But the real question is, if you take a person who is of normal weight, who does not have type 2 diabetes, but maybe has a higher risk for Alzheimer's disease, and you microdose them, so you're giving them 2. 5 milligrams per day, which, by the way, we are doing in some patients for obscure metabolic condition without obesity. We have patients who have diabetes but are already at very low body weight. We have two patients actually in our practice in this regard. After lots of detailed back and forth machination with Ralph Dufranza, who's a previous guest on the podcast, we realized that at least one component of the drug regimen for these patients was going to be a GLP-1 agonist.

Now, it seemed very counterintuitive to give Trizeptide to people who have a BMI of 23. But we've been able to do it without them losing weight. So again, very careful strategies around nutrition and the effect on their diabetes is profound.

They're looking more metabolically healthy.

Oh, my God. These are really interesting cases that maybe at some point, obviously in a de-identified way, it would be interesting to talk about where you have OGTTs that are unrecognizable. You simply cannot believe the degree of metabolic dysfunction in a person who otherwise looks the way they look. And in one case in particular, it was so confusing that even after all the genetic testing we did, we simply couldn't figure out an answer for this. We couldn't understand where the beta cell fatigue was coming from, absent a formal diagnosis of type 1 diabetes. Within three months of being on 2. 5 milligrams of trisepotide, this individual's OGTT had almost normalized, and I suspect by about six months it will.

That's fascinating.

We've managed to do this without any weight loss. This, to me, is the interesting question, which is when you look at some of the Alzheimer's biomarkers, which are improving, improving significantly, it begs the question, should this be part of the playbook for an individual who's at high risk? Especially given that we now, I think, really understand how to make sure people don't lose weight and don't lose lean mass, and therefore, I suspect, don't lose bone density and all these other things that matter.

Or like you said, if you're doing this microdose, maybe you're not going to be as satiated. You'll still have somewhat of an appetite because you're on such a low dose. Maybe you're going to have a little bit of an effect.

We've also seen some There are weird things anecdotally. Patients have told us that when they inject in the abdomen, the fat, the subq fat of the abdomen, basically the anorexic effects are greater than if you inject in the leg or butt. We looked into this and there was some mechanistic data to suggest that maybe you're getting vagal tone when you inject in the abdomen. Again, I just don't know if any of these things are correct. They would need to be studied. But again, that would be a very important piece of data. If there's a location you can inject this where you minimize the anorexic effect of the drug. Again, for some people, that would be a feature, not a bug. For some people, that would be a bug as opposed to a feature. You have to understand how to use the tool.

Yeah. This just reminded me of something that we should have pointed out. Talking about the protein requirements, grams per kilogram bodyweight. I do think it's important. We were just talking about obese people.

Yes, I'm glad you brought this up.

Yeah, exactly. Where it's like, most people aren't going to do a DEXA scan to see what their lean body mass is. But ultimately, I think, and I've talked to a variety of experts, Brad Schoenfield, Sue Phillips, they agree that really, if you're someone that's overweight or obese, you shouldn't be calculating it based on your actual weight because your protein is way too high. It's more like your target weight. If you empirically could measure your lean body mass, that would be better. But yeah, I just wanted to point that out.

Yeah, and I'm glad you did. That's right. For most people, probably not much of an issue. But if you're at 300 pounds right now and your ideal body weight is 220, you don't need a Dexa to figure that out. A Dexa can help, but most people who are 300 pounds remember, Gosh, at the end of high school, I was 220. That was my good weight. Or maybe at the end of high school, I was 200 pounds, which is I'll probably never get back into those genes again. But by the end of my freshman year of college, I was 220. That was a good weight for me. And then it's just gone downhill from there. You had this orthopedic. There's the story of how you got to be 300 pounds. Yeah, most people can figure out. 220 is probably my goal weight, and that's what I should be targeting. You made a great point, which is, how do we reconcile the following? So Caloric restriction as an intervention, as a geo-protective intervention, is the oldest one in the book. I'm not really aware of a non-genetic intervention that has, from a longer-standing perspective, produced a consistent outcome in terms of laboratory animals, where you restrict them in calories and they're going to live longer.

Again, to my knowledge, there are only two interventions that have extended life across all four models of organisms, from yeast worms, flies, and mammals, rodents. That is caloric restriction and rapamycin. They have something in common, which is they both result in the downregulation of MTOR. We also know that an amino acid you just mentioned a moment ago called lucine is the single most important of all the amino acids at turning up MTOR. How can we reconcile the idea that protein seems to be good for you, but MTOR going down seems to be good for you, at least in another way. Well, for one- I'm being very facetious because you know I know the answer to this question.

It's like, oh, gosh, where do we start? Because let's ignore the worm and the fly and all that because who cares? I mean, even the rodents, it's a stretch. You know what else turns on MTOR? Exercise. Physical activity, mechanical force turns it on in our muscle. We know exercise is one of the best things that we can do for our health. I think here, I think for Simplicity, the best way to think about this is that you want MTOR active in your skelet muscle. You want it active in your skelet muscle. You don't necessarily always want it active systemically. But if you are exercising, if you're moving around and you're taking your protein, it's going to your muscle. We know that for a fact. I talked about anabolic resistance and how exercise can counter that. Well, it's increasing the leucine transporter, the expression of leucine transporter. It's causing leucine and other branched chain amino acids to go up into the skeleton muscle. Multiple human studies have shown this. These are tracer studies, beautiful data, no argument. Exercise causes leucine and other branched chain amino acids to be taken up into skeletal muscle, where you want it to be so that it activates MTOR, increases muscle protein synthesis.

When it comes to deactivating MTOR, whether that's through protein restriction or rapamycin, that would be like an hour's long podcast talking about all the nuanced data there because there's all sorts of differences with sex differences in rodents. You're aware of all this data. My biggest thing here with the protein restriction, let's talk about one. I I had spent six years in grad school working with mice. I did a lot of animal studies. These mice are in a small cage. They are not physically active. They are not running around. I mean, they move a little bit.

They're not under threat.

They're not under threat. They're being fed adlibium. They're just being fed as much protein as they want.

Perfectly thermo-regulated.

They're not being exposed to influenza or COVID, whatever, viruses, anything that's going to take them out for a period of a couple of weeks. They're in a sterile environment. They're happy. They're happy, and that's it. People are not mice. We talked about earlier, as we get older, we're being exposed to infectious diseases. Things are going to make us immobile for a period of weeks. That is devastating to us, especially when you add them up and they happen this year. Then the next year, it happens again, and then you're just losing that muscle mass. Then you reach that disability threshold. You talked about Luke Van Luhne talking about those curves. It's very clear. I mean, you can see the data where there's a disability threshold. You get enough of these catabolic crisis events where you're just immobile for a certain period of time because you've had a surgery or you've had the flu or whatever has kept you inactive. That doesn't happen to these mice. Protein is much more important to humans because we, of course, need that muscle mass and we need to bank it early. We established that. I think that's a really important difference here is that we can't just look at the data in mice and go, Oh, you can restrict them from protein and they live longer and they're fine.

Well, they're not going through these catabolic crises. They're not going through these points of not moving for a period of time for losing all this muscle mass, then that happening, and they reach this disability threshold, and then it's very different. I think that's first and foremost important to point out. The second thing is that if we're talking about protein intake, I think that you and I agree the optimal scenario here isn't a sedentary person just sitting there eating as much protein as they want. No, they need to be moving, physically active. That's the whole point. You're supporting your physical activity by increasing your protein intake. In that scenario, again, the amino acids that are activating MTOR are going to skelet muscle. That's been shown. Lucine is going into skeletal muscle. So who cares if you're taking in more I think that's such an important point, Rhonda, that I would even go one step further, which is if you told me, come up with the optimal nutrition strategy for the individual who is active, and then come up with the optimal nutrition strategy for a person who is going to be sedentary, they would be very different.

I'm going to try to talk that sedentary person into not being sedentary. But if at the end of the day, I can't, if that individual says, I don't want to do anything. I just want to sit in front of my computer. You know what? It probably makes sense to be a little bit caloric-restricted because I can't solve your metabolic challenge through activity, but what if I could at least solve it through nutrition restriction? Again, I think it's the inability of people to understand that those are very different states. You cannot treat those two people the same way.

Right. There was a study by Valtralango, of all people, years ago, came out. It was a large cohort study looking at dietary protein intake from vegetable versus meat sources. We all know that meat sources have higher levels of essential amino acids like leucine. All-cause mortality was looked at and the same statement that you've heard millions of times from other studies about, okay, vegans have a lower all-cause mortality than meat eaters. Well, it turns out when you actually start to analyze analyze the data and correct for a lot of confounding factors, meat eaters that were physically active, were not obese or overweight, didn't smoke, didn't drink excessive alcohol. In other words, they didn't have all these unhealthy lifestyle factors. They had this same mortality rate as the vegans. I think that also is a good point here where it's like, okay, if you're going to be a sedentary person that's smoking, if you have unhealthy lifestyle factors, maybe you don't need to be so obsessed. You definitely want to make sure you're at least getting the minimal amount of protein because you don't want to be in the deficit. But you don't want to necessarily just be constantly activating MTOR if you're just going to sit around and smoke and be overweight and not do anything with that protein.

Yeah. The other thing I think that is missing from this discussion, this is where I think inflammation serves as a great analogy I think most people on the surface understand that a constant on state of the inflammatory system would be bad. But of course, if you had no inflammatory response, that would be also bad. The ideal state is inflammation when you need it, otherwise off. Inflammation when you need it, otherwise off. I think that's probably the right way to think about this, which is we want MTOR on when it has a job to do, and we want it relatively silent when we don't. I think if rapamycin is geo-protective, when I say if, I mean in humans. I think it's unambiguously protective across most species, but we still don't know if the species of interest is going to benefit from this drug. We may never, by the But it's probably working by tamping down the chronic inflammatory component of what we see with MTOR activation, which, by the way, might actually involve inflammation as well as one of the many things. There's also this challenge of trying to get folks to understand the difference between chronic and acute things.

Cortisol, great example. Cortisol, vital hormone. The appropriate rhythm of cortisol is essential for life. If you took that away, you would actually be dead. That's called Edison's disease. But cortisol Well, constantly being on would also be a problem. That would be Cushing's disease. So both extremes, bad. It's, do you know when you need it and what it's supposed to do? I think the same is true with MTOR.

I'd also like to see data comparing even if it's animal data, comparing giving rapamycin or somewhat inhibiting MTOR versus physical activity, making them run on a treadmill, being physically active. Because if you look at a lot of the protective effects of rapamycin, I'm like, this is what exercise does. An exercise does it better. I'm just not convinced that someone who's already bought into how important exercise is, both cardiovascular and weight training.

Well, Eric Verdon made a very interesting comment on my podcast a while ago. Eric is in the camp that he does not believe Rapa will be geo-protective in humans. He talked about the longevity quotient. For listeners, the longevity quotient is a plot, a very famous plot that on the X axis puts body size and on the Y axis puts lifespan. And you just plot all the organisms on this thing. And as a general rule, it rises up and to the right. The larger an animal is, the longer it lives. And it's a pretty straight line. In fact, we should find a good example of it and link to it in the show notes. But there are always animals that punch above and below their weight. So there are animals that fall off that line, either too high. So these are animals that live much longer than you would expect based on their body size. And there are animals that punch well below their body weight. They live much shorter than they should based on their body weight. Well, it turns out two interesting examples are mice and humans. Mice live on average two years. I forget the exact number.

They should be living close to four or five years, I think, based on the longevity quotient line. They are punching well below their weight. And humans, we live 80 years. We should probably be 40, according to the data. By the way, we did live 40 years until modern medicine came along. So maybe we were totally on the curve correctly until medicine 2. 0 came around at the turn of the last century, and basically over five generations doubled our lifespan. Eric argues, I think this is a very interesting argument, rapamycin disproportionately works well in animals that are below the longevity quotient. So that's why it works so reproducibly in mice. But he argues it might not have any effect in humans because we've already captured so much of our genetic potential in terms of lifespan now, that the idea that Rapa would give us an extra 15% of life, he feels It's just hard to imagine. Again, it's a theoretical argument. It's super interesting, but I'd never heard it in relation to the longevity quotient before, and I thought it was very much worth pondering.

Yeah. Well, that's interesting. I've also seen data with Rapa myasin given to people that were undergoing resistance training, and it blunted, obviously, some of the muscle protein synthesis, as would be expected. I don't remember the dose of rapamycin. It wasn't super high, but to me, that was enough to be like, well.

Yeah. Then the question, of course, is, is there a way around that? Is there a way where you could intermittently dose it? You just take it once, you time it so that it's not in proximity to a bout of resistance training by a couple of days or something like that. But yeah, there's a lot there. The great expression I heard recently, which is, Mice usually lie, monkeys sometimes lie, it's humans we care about. That was just fantastic.

Well, to get back to the MTOR story, I think that recent study, I don't know, it was in the last couple of years it came out. It was the animal study where they gave mice 25 grams of protein, and MTOR was activated in macrophages, and it was like this whole story was pieced together about- Twenty-five grams of protein? Sorry, maybe it was the equivalent dose. Equivalent, okay.

It was the human equivalent dose. I was like, wow, they're eating their body weight in- The human equivalent dose was 5 grams, yeah.

But it was essentially arguing that atherosclerosis was being caused by protein. I'm like, Are you kidding me? For one, we know atherosclerosis, the bigger story there, is not protein. But again, it It comes down to this whole activating MTOR in systemic circulation versus the Luzine going to the muscle because you're physically active. Keep in mind, those transporters, the Luzine transporters, they're pretty sensitive for quite a while. I mean, you're talking about at least 24 hours, maybe even longer, but definitely 24 hours.

I think the MICE atherosclerosis studies are very dangerous. We have to be very careful. They have a very different lipoprotein system than we do. They evolved in a totally different manner than we The amount of protein they require is totally different from us. I'm always really wary when I see these studies that are using the mouse model of atherosclerosis. I understand why we do it because it's much easier and cheaper than looking at primates. Obviously, we can't do these studies in humans, but you can find a lot of things in mice when it comes to atherosclerosis that don't seem to matter whatsoever in human biology. I would chalk this up to one of those examples.

Then there you have it. I mean, that's a lot of the controversy around protein being bad for you and activating MTORs coming from that study. Then there's countless studies on cancer increasing with IGF1 and MTOR. Again, same deal where IGF1 exercise is causing IGF1 to go into the brain, to go into muscle.

People also don't appreciate how short the half life of IGF-1 is. It's a staggeringly short half life molecule. Oh, really? Oh, yeah, it's insanely short half life. What's the half life? When administered systemically, it's on the order of minutes. Okay. Yeah. By the way, administering IGF systemically as a lousy way to get it to the muscle. You want to think of it almost as a paracrin thing where it has to be delivered into the muscle. Look, all roads for me still point back to this idea that, and I know you would agree with me, so it's not going to be that controversial, but exercise is the most important drug. I'm just not aware of a drug in quotes that is better than exercise. I know there's this enormous effort to figure out a way to put exercise into a pill. I just can't imagine it'll ever happen. It's not. There might be several pills that come out of it. We might figure out a way to make cloth, though. We might figure out a way to make BDNF. We might figure out a way to deliver IGF directly to muscles. There might be a whole bunch of little things.

There's like 500 molecules.

I don't know if you remember this. I'm dating myself, but I don't know if you remember Irison. Yeah. There are no shortage of these things. Right.

There's so many things going on for sure that is beneficial with exercise. To bring it back to the protein, I think that they go hand in hand. We're talking about being optimal, increasing our health span, increasing our lifespan, having a good quality of life, then you're talking about having a higher protein intake to support your physical activity, period. Athletes, they're some of the longest-lived individuals on the planet. We talked about this in our last podcast. Olympic athletes live on average five years longer than the Gen population. Same goes with a lot of these athletes playing these indoor team sports. There are several studies out there looking at elite athletes, including people in the NBA, Major League Base, a lot of these big professional sports league, they're taking in at least 2 grams per kilogram of protein per day. Clearly, protein isn't killing them. In fact, they're living longer than the general population. Again, it comes down to that Exercise is the king, right? Exercise is the most important thing, but you need a protein to support that physical activity. I don't understand why anyone's arguing about that. What's the argument?

Despite all the flak I'm taking, I'm going to just defend this one and continue. By the way, if new data emerge, I'm always happy to change my mind. I've changed my mind about so many things. It is absurd the number of things I've changed my mind on. I've changed my mind on GLP-1s, I've changed my mind on saunas. I can count the list of things I've changed my mind on over the past 10 years. If there are data that will make me change my mind, I will stand up here with a straight face, and I will eat crow, and I will tell you that I've changed my mind. But I'm going to stand by my recommendation, 2 grams per kilogram per day. And my rationale, again, I explained it earlier in the podcast, but just to restate it, if you aim for two on the day you fall short, you'll still be at 1. 6. If you aim for 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 next day because the downside is asymmetric compared to the upside. So that's our recommendation clinically, and that's how we work with real people in the real world, not on our Substack pages, to try to help them live a longer life.

Yeah. Is there anything else with the protein?

No, let's never talk about this again. Pending new data that fundamentally changed the way we think about it. All right, I want to pivot to another topic, which you may be single-handedly more responsible for the buzz on this topic than anybody else I can think of, and that is creatine. Should we start with... Well, first of all, just tell me, what got you interested in this topic? You're not the typical demographic, no offense intended by that, but when I was in high school, and I'm probably 15 years older than you, we, as young boys in high school in the '80s, were mainlining creatine like it was our day job. But here's the thing, I don't remember why.

It must have been because your friends were doing it.

Well, no, it must have come from bodybuilding magazines. I don't know where we got the information I was thinking about this the other day because I knew we were going to talk about this. I was like, Okay, there was no internet. What was our source of truth? It was muscle and fitness. There must have been something in muscle and fitness that told us this. Then you know what I realized we did? We would hang out at supplement stores. We'd literally go in, and the supplement stores always had some big bro in baggy pants that taper down to his feet, and he was barely wearing a shirt, and he was yoked, and he was explaining to us. We were at the altar of this guy, and he was telling us, there's creatine monohydrate, and then there's creatine phosphate. At the time, everyone said creatine phosphate is better, and you have to load 30 grams a day for two weeks. Then you go into your maintenance phase at five grams a day, and then you repeat the cycle every eight weeks or whatever it was. We were buying this stuff by the truckload, and this is almost easily 35, 40 years ago.

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

You just made a really important point, and I'll talk about my journey in a minute, and that is it's one of the most well-studied sports-related supplements ever. There's just decades and decades of research out there on creatine. A lot of it has to do with muscle. We'll talk about the brain, which is my interest. But it's one of the tried and true. I mean, it's safe. I don't know that there's any other sports supplement out there that's as safe as creatine. I don't think there is. That's an important point. My journey with it began with my obsession with increasing my resistance training.

Like your performance or your hypertrophy or your recovery, what specifically?

Everything that we talked about in the first half of this episode, where I realized that I was so focused on endurance training for long-term health, for brain health, that I neglected my muscle mass and thinking about how important muscle mass was for long-term health.

You've chronicled this pretty well on your social media. You've got videos of you deadlifting. You're really embracing this.

Yes. Yeah, awesome. After having a couple of experts on and just when I have an expert on, I read the literature voraciously. I just dive in. I want to be in it. It's part of the fun. I love it. I get to learn all this new material that I'm interested in. I finally realized that I wasn't doing enough. Training, resistance training. I have a personal trainer now. I'm doing resistance type training. I do a CrossFit type training for at least three hours a week. I'm doing now. It started out, I was doing 30 minutes a week. I've gone from 30 minutes to three hours. A week. Big difference. That's when I became really interested in creatine, where I was like, Okay, I know this one supplement is obviously shown to benefit people that are working out. I didn't know why everything until I got into the ledger, but That's what got my interest into creatine. Most people know creatine is stored in our skeletal muscle as creatine phosphate. It's essentially used to rapidly recycle ATP, adenosine triphosphate. This is the major energy currency in our cells. Creatine phosphate is able to help rapidly recycle that so you can make energy quicker.

Very relevant for a lot of scenarios, including high-intensity interval training, resistance training, even endurance training because it decreases recovery time because you're recycling that ATP. It's really relevant for a lot of scenarios. We do make creatine endogenously. That's another thing where it's like, this is a molecule that we make in our body. It's not like a dangerous thing that I'm really scared of. We make about one to two grams in our liver. Our liver's make about one to two grams a day. Then we can take in another, depending on how much meat we eat. Meat is the major source of dietary source of creatine. Vegetarians 100% rely only on their one to grams a day. They're probably the population that benefits the most with supplementing with creatine. There's just countless studies out there showing this because they're just not getting anything from their diet, essentially. I mean, there's negligible whatever is in plant.

Does the type of meat matter? Does fish versus beef versus chicken? I would imagine there are differences.

Yes, there are. There are differences. Like beef- Beef would be the most. Beef would be the most, yeah. It's probably why people on a carnivore diet, they just get so jacked. They're getting the creatine, they're getting protein, and they're working out, and it's this combination, right? They're just getting so much.

Do you have a sense of if you eat a 12-ounce steak, how many grams of creatine would you get in there?

People can figure that out with Google. Generally speaking, on average, people are getting in their diet Probably like 1-2 grams.

Additional. So you've got your endogenous plus- Yes.

Then you can supplement on top of that. This is where I would say for many, many, many decades, the literature was all about the effects on exercise performance. Because the muscle is a big consumer of energy, especially if you're working the muscle. I'm totally just summarizing this. I'm not going into every single detail, but generally speaking, five grams a day of creatine is enough to saturate your muscle tissue. It takes about a month, maybe three weeks to actually fully saturate it if you're doing five grams a day.

Hence the bros that were telling me to take 30 when I was 13. That might have been overkill.

It's coming from the fact that in these studies that have been done, because people haven't been taking the five grams a day for three weeks, and they're doing this short term, weeks long study, they want to quickly get their muscle saturated. That's why they do that loading phase. Most people don't have to do that unless you're doing some competition and you need right then and there. Generally speaking, it's just not necessary, and you really just increase the risk of GI distress.

Our thinking today is just take five every day, and then you should be all right.

Well, that was my thinking up until a few months ago. All right. I was taking for the last year and a half, I was taking about five grams a day. The evidence there is that the creatine is essentially improving your exercise performance in that you can do one to two more reps, or essentially the volume of training goes up because you're recycling that energy quicker, you're able to do more, and that is why you then get gains in muscle mass and strength. It's not like the creatine is acting like protein. It's not increasing muscle protein synthesis if you're just a couch potato.

You have to do the work.

You have to do the work, right. And the reason that you do increase the muscle mass and strength is because you're able to do more work. It's pretty obvious. Anyone that For me, with my crossfit, it really is useful because there's a lot of explosive training, a lot of hit. For me, it was pretty obvious that it was having an effect. Of course, there's probably a mixture of placebo in there as well. I'll definitely admit that. But then I I started getting interested in some of these brain studies. As you know, I'm very interested in brain health, neurodegenerative disease risk, anything that can improve cognitive function in a safe way, like any safe neutropic. That's where I really started to get interested. This has built up over years where I was getting interested in the brain effects, even though I hadn't been supplementing with it. I had been keeping an eye on the literature. Finally, when I started using it, I got pushed over. I'm like, Okay, I'm all in. I want to get into this.

You felt like you got all in because you felt a difference, or you were like, Well, look, I'm already taking it for these muscle purposes. Let me really now go deeper on the cognitive science?

Yes. I was already like, first of all, the literature was clear with the muscle. There's a lot of literature. You can't deny it. You just can't.

It is a little odd. There aren't that many things that show up where the consistency of the studies is always in the same direction. Really, what you're basically looking at is the magnitude or the effect size, but you're always on the same side of the tornado plot.

Exactly, right. When we're talking about 40 years or whatever of research, that's a lot of data. With the brain, so for one, your brain does make a little bit of creatine as well. Something I don't remember. I think it's somewhere between one to three grams a day. But the data on the effects of supplemental creatine on the brain isn't dating back as far. You do have to take the data with someone of a grain of salt because there's a lot of small studies, and they're not like, you can't hang your head on it. This is the end all be all.

Let's talk about some of the measurements. I think one of the advantages of studying the effects of creatine on physical performance is we have really good objective measurements that you can demonstrate in a short period of time. You could do a 12-week study, and in just 12 weeks, you could objectively, unambiguously, determine if there was hypertrophy and if there was an increase in performance. How do we do that on the cognitive side? What are the data that you've been looking at that have given you an increasing level of confidence?

Okay, well, first, let's talk about dose because that's important. I think that that was where initially, when researchers were looking into the effects of creatine on the brain, the five grams a day didn't seem to be doing anything in terms of getting creatine into the brain.

Creatine is crossing the blood-brain barrier. That's established?

It is. However, the muscles are greedy as hell.

Those lovely greedy muscles.

Yeah, the greedy muscles. When you're taking in up to about five grams of creatine, they're consuming it. They're taking their share.

Especially if you're training.

If you're training, it's like, yeah, exactly. But even if you're not training, it's still going to muscle. But yes, especially if you're training. There was a German study that was published a few years back that did dose-dependent effect and looked at creatine levels in certain brain regions.

Naive question. Are they using an isotope? Are they labeling the creatine?

I believe they were using an isotope.

They're not using CSF levels or anything?

I believe it was an isotope. But don't hold me to it because I don't remember exactly. You need more creatine. I know. But 10 grams was where creatine was now- Was not rate limited. Yeah, exactly. Now, you were increasing levels of creatine in the brain. Pretty sure it was isotope labeled. Essentially, 10 grams- Is it double it? You have to double that. That's where I was like, okay.

Does that mean that you're going to get mixed results if you look at the cognition literature, because you're going to have some studies that were underdosed. If you have a study that was done at five and it shows no effect, you're going to come to the wrong conclusion potentially.

Bingo. Just like with any supplement and/or drug dose matters. So yes, that is the case. But also it's important to point out, just like with muscle, you have to be stressing your muscle for creatine to work. You're basically putting in the work and you're able to put in more work. And that's why you can increase muscle mass and you can increase strength. With the brain, it works in the background of stress. And what I mean by stress is sleep deprivation, psychological stress, like you have an exam, marital. I mean, whatever psychological stress, emotional stress, sleep deprivation is a big one, neurodegenerative disease, or anything that's compromising brain function. That's where creatine really shines in terms of cognitive function, and we'll get into measurements. But I think that's important to point out. This is my argument. I feel like I'm constantly under stress. I think most people are constantly under stress.

Anybody listening, if you're not under stress, I'd like to hear from you. I want to know what you're doing. Same.

Even just diving into the scientific literature, what we do every day learning, that is the stress. The brain consumes a lot of energy as well.

20% of our total caloric intake goes to an organ that weighs less than 2% of your body weight. It is the most insane statistic of the human body.

Totally, which is why it makes sense that giving your brain extra creatine, which can recycle that energy quicker, would help, particularly in the background of when you're using more of that energy. If energy is being triaged to whatever stress and the hormones and whatever is going on, fill in the blank. The studies that typically are looking at the effects of creatine on cognitive function are looking at processing speed. They're looking at a battery of tests that are typical of any fill in the blank supplement or treatment that is either going to improve cognitive function, memory being another one. Processing speed is a big one, too, I would say that creatine has been shown to improve. But again, really Really, it's in the background of stress, whether that's stress being aging, so older adults. So aging is a stress, brain aging. So older adults seem to benefit from taking exogenous creatine or supplemental creatine. And people that are sleep-deprived. That's another one. That's a really big one. In fact, there's been a few studies that have shown people that are sleep-deprived, if you give them... This was on a per kilogram body weight basis. So I think it was 20 to 25 grams of creatine that were given just based on their body weight.

But if they were sleep-deprived and given that creatine, not only did the cognitive deficits that usually occur when you're sleep-deprived not occur, but their cognitive processing speed was improved more than baseline. Now, this is a small study. If you, Peter, were to go to the study and look at this, you'd be like, This is a small study. And I agree. We can't just hang our head on this one study.

Who's doing these studies? Because there can't really be any financial incentive to do them. Creatine is ubiquitous. There's no IP around it. I want to give people some advice on how to go buy creatine, because if you go to Amazon, it's like, Which one do I buy? But who's taking the mantle on trying to understand this? Because it is an important question. And if you've got something that's insanely cheap, completely safe, has other benefits in the body anyway, and all we're really trying to figure out is, hey, should we all just be doubling our dose from 5 to 10? It'd be great to quantify the effect size and stratify patients that we need to be reaching out to, because Again, not everybody listening to us is doing this anyway. It's just one more thing to ask somebody to do, which comes at a cost. There's a psychic cost to just asking people to do more stuff, and it's one more thing you got to do. Again, this is low-hanging fruit in the world of biomedical research. It is.

Darren Kandau is someone who he's getting into the brain stuff. I think there's quite a few people that have been doing muscle research who are now... It's opening doors for them where they're collaborating and they're reaching out to people that are doing more neuroscience, and it's exploded.

This got like Dom Degasino's name written all over.

That's a really good point. It totally does.

We got to talk Dom into doing this.

There was a pilot study that came out. These are researchers that I don't know necessarily, and some of them are pretty junior. But there was one that came out with people with Alzheimer's disease, and they were given 20 grams of creatine, and it improved cognitive function in these patients with Alzheimer's disease. I think there was also placebo control as well. Then they took those same patients and then had of them exercise in an improved strength and improved lean body mass.

I'm just going to be skeptical. I still think that the name of the game is prevention, where I'm most interested. Of course, that's the hardest thing to study. But when we think about the energy crisis that is happening in a brain with Alzheimer's disease. While there are, I think you and I would agree, there are probably many paths towards AD. There are inflammatory paths, there are lipid-mediated and vascular paths, and then there are these more metabolic paths. But when you take that individual who is most susceptible to the metabolic path towards dementia, and 10 years earlier or 20 years earlier, you're giving them a substrate that is augmenting ATP creation, yeah, I get it. That's the hardest thing to study. That's also the single most important question in my mind.

Totally. Prevention is the name of the game for sure, 100%. Unfortunately, there's a lot of people's parents out there that have it right now because they missed the boat on prevention. Those people are obviously... Their kids are willing to do anything to help It's terrible, right? I think the reality here, and the point I want to make, is I think that creatine for the brain is the most interesting aspect of this area of research right now, at least for me. I certainly think that there's really no downside to doing 10 grams a day. Now, in some cases, sleep deprivation. I just got back from China about five days ago. I've been doing 20 grams a day, 15 to 20.

I remember as a kid, I never had the GI side effects with even 30 a day. But for some people, is 10 to 20?

In one dose, it would probably affect a lot of people's GI. I do five gram doses.

You'll just put the five grams into water?

I put the five grams into water or tea, and then I just take it like that. I do it mostly before noon. I don't know if this is placebo, but I don't get sleepy in the afternoon anymore. If I only get five grams, I get the sleepiness. Now, again, it could be complete bias, and who cares?

If it's not- If the placebo is working for you, take it.

Exactly, because it's physiologic, right? I mean, it's a biological mechanism that's working for me. If you listen to this episode and it works for you, that's great because there's really no downside. In fact, I think we're going to get more and more evidence out there that it's going to be beneficial, and 10 grams is going to be the new- The new baseline. 5 grams. Yeah, it's going to be the new baseline.

But if you aren't in this state of jet lag, 10 grams for a day, you do two shots of five and you're feeling great.

That's what I do, 10 grams a day.

Let's talk a little bit about brands. Are most of the companies out there that are otherwise very reputable in making making supplements, so whether that be Thorn, Momentous, I've lost track of all the names of the companies out there that make supplements. There are a handful of supplement companies that actually really seem to be credible. Do you have any difference between them? Do you always look to make sure that CreaPure is the active ingredient within it, or does it matter?

I think the most important thing is that it's creatine monohydrate. The reason people like CreaPure is because it's pure. But what I like even more than that, is NSF certification because there's rigorous testing to make sure there's no lead contamination and these heavy metals and things that hitchhike on a lot of these supplements. Personally, that's what I look for. I think CreaPure is great too, depending on whatever brand is using CreaPure.

Yeah, lots of brands are using it.

Exactly. Nsf is what I look for. I use the thorn.

There's no reason you can't have both. You could have CreaPure in an NSF-certified product. Totally, for sure. One thing I want to call out that one of the members of my team was sharing with me yesterday, apparently, there are a whole bunch of creatine gummy products out there. For the obvious reason, they're very popular, But there was a third-party test. Well, why don't you tell what they discovered?

Yeah. I mean, it was essentially there was third-party testing, looking at actually quantifying the levels of creatine monohydrate in these gummies, and there was essentially none in 95% of them. That does, I think, translate to gummies in general. I've talked to vitamin manufacturers, and they've said it is incredibly challenging to get an active ingredient into a gummy, and you're heating it There's the heat component that's degrading things. Gummies, unless you can find a third-party tested gummy that actually has the amount of creatine monohydrate in it that says on the Nutrition Facts label, I would avoid a gummy.

Yeah. Also, the thing about this whole gummy craze that drives me bananas is you have to ask the question, how many gummies do I need to eat? Look at the chalky white creatine powder. Look at what five grams looks like and ask yourself, how many gummies would I to put this into such that they would be palatable. Then the question is, do I really want that many gummy bears? What am I doing to my teeth?

Yeah, what else is in the gummy?

How much sugar do I need to eat that's totally unnecessary? If I'm going to have sugar, let it be good. Give me a nice piece of chocolate. Give me a piece of carrot cake. I'm not going to squander my sugar calories on gummy bears that are not even giving me creatine.

Don't eat the gummy. You need the powder. Thanks for bringing that because also capsules, you're going to have to take so many capsules to get. I say the 10 grams or even the five if you're just looking the muscle effects, you're just going to have to take a lot of capsules. That's also an important point. I also think that the vegan thing and vegetarian is another really important aspect.

If you take them to 10, they should be fine because they're at least offsetting the couple grams.

No, I'm just saying it'll change it. I have so many vegan friends that it has literally changed their lives. My phone blew up. I couldn't believe the magnitude of the fact that these women were experiencing was way outsized compared to what I was getting. I noticed an effect. I mean, it was like, unreal.

How long had they been vegan?

One of them, not that long, maybe two years, but the other one just- Most of her life? Yeah.

I'd be interested. The one who had been vegan for two years, when she all of a sudden got creatine back, I wonder if that was a short enough period of time that she was like, Oh, my God, this is what I used to feel like just two years ago, or there's probably too many confounding variables.

She's always calorically restricted, too. I don't know how much protein she was really eating when she wasn't. Yeah, I got it. It wasn't. Yeah, but that's a good question.

Talk to me about kids. My daughter is 17. She's really training hard. I mean, she runs across country, she does track, she's in the weight room. Is she too young? No. Should she be taking creatine?

Yes. There's studies out there on kids, children younger than 17.

My boys who are very active in sports. I'm giving it to my son. Okay, how much?

If I remember correctly, it's like 0. 1 grams per kilogram bodyweight. I give my son two and a half grams. Okay. Again, there's studies out there. It improves. Agility is a big one and speed. A lot of these studies were done more like an endurance because kids aren't lifting weights. So it improves agility and speed.

Would you, for my daughter, give her five?

Yeah, she's tall, too.

She's studying hard. Like, does she just need the full 10?

Exactly. She is almost an adult.

I think she's done growing.

If it For me, I would do 10. If it was my daughter. There's actually some studies that have been done in college students who are taking a test and stuff. And of course, you're sleep-deprived when you're studying for the test and the creatine improves test score. So I'm all in on the creatine.

My creatine budget, literally, the household creatine budget just went up by 4X.

Same happened to me six months ago or so. Again, the harm that people claim is unfounded. The kidney problems. First of all, as a physician, you know what the problem is. People are looking at creatinine. If you're supplementing with creatine, you got to tell your physician.

Well, the other thing is physicians listening to this, please make this another reason to just look at statin C, please. I'm sure the test costs an extra dollar. It's worth it. Statin C is a far more accurate way to measure and estimate GFR, and you don't have this problem of getting the confounded creatine levels increased. I know we have to get you out the door relatively soon because you were giving a talk today. But if we have a little bit more time, I want to talk something about a topic that is near and dear to both of our hearts, which is temperature. You know my journey on the sauna train. I was probably the biggest sauna skeptic for many years, not because I didn't love it. I've always loved the sauna. I just had a hard time believing that the data were causal. I was just like, There's too much healthy user bias in here. But over the last five years, as I've looked closer and closer at the data, while I can't comment on the effect size, I think it's very difficult to comment on the effect size from all the epidemiology. It's very difficult for me to believe that there isn't a positive effect in terms of at least cardiovascular disease and dementia.

Those are my priors. My priors are, I'm now in a place where I actually view sauna as an intervention that can help an individual reduce their risk And for me personally, because I don't really worry about cardiovascular disease anymore, it's so easy to manage the risk around that otherwise. But dementia is a very difficult risk to manage because there's fewer things we understand about the causal pathways to get there than we do ASCVD. So in many ways, I'm in the sauna, not just because I enjoy it, not just because it's a wonderful social opportunity to be with your spouse, if that's how you choose to do it, but because I'm also banking a little bit on, hey, I want to get some benefit to my brain. So tell us where you are currently, because you're one of the people who I think keeps up with this literature more than anybody. Tell us, if anything has changed in your mind, one way or the other, both in increasing confidence, decreasing confidence. Just update us on where you are.

Yeah. I am still a huge proponent of using deliberate heat exposure to improve your health, both cardiovascular and brain. I do think that the physiological mechanisms are somewhat, in some ways, mimicking some aspects of moderate intensity cardiovascular exercise, and that is how it is improving cardiovascular health and also an aspect of that brain health, cardiovascular fitness that's been shown. There's been not only observational data, but there's been intervention studies looking at endurance, getting someone on a stationary cycle, and then adding the sauna on top of that. And VO2 max improvements were greater in individuals that are also doing the sauna right after their training. Anything that improves cardiovascular health is going to improve brain health. But there's another aspect to the story here, and this dates back to the origins of one of my first biology experiments I did when I was actually a technician at the Salk Institute before I went to graduate school. And that has to do with the heat shock protein response. We do know that heat stress in the form of either hot baths or going into a hot sauna, infrared sauna, a little different, you'd have to stay in there a long time to get a real heat shock response.

But if you're in 163 degrees Fahrenheit sauna for 30 minutes, we know that heat shock proteins increase about 50% over baseline.

What would be the equivalent exposure in steam or water?

In the water, it's about 104 degrees for 20 minutes, shoulders down.

Twenty minutes?

Yeah, about 20 minutes.

Then presumably, if you're in a hotter dry sauna, less time is needed?

Presumably, we don't have that data. I'm just quoting the empirical data that we have.

Tell me more about the IR, because there are no questions I get asked more than, hey, are all the benefits you're talking about, which all seem to come from studies in dry sauna, are they also applicable to infrared saunas? To which the only data I can find is if you're using infrared, you actually have to rely on the change in skin temperature. Whereas in dry sauna, we can look at time and temperature and humidity. If I know the temperature of the sauna, the humidity of the sauna, and then the duration that you're in there, I know how to measure the effect size. We can't do that in IR. We looked at some data that looked at basically thermal skin change. I can't remember the numbers, so I don't want to get it wrong. It was either five or eight degree increase in skin temperature was necessary to produce similar benefits. Do you know about this?

Not that. I don't know specifically about that, but I do know most of the studies that have been done comparing, and there have not been many, maybe three or four that I can think of, they have compared a regular hot sauna to infrared sauna at the same amount of time. So In other words, the dose is the same. Obviously, the temperature difference is pretty vast. Depending on the study, the hot sauna could be 160 or it could be 175 or 180, and the infrared is 140 or something like that. A lot of variation in terms of the temperature of the saunas. If you're looking at, in fact, there's one study, the title of something like Infrared Saunas does not mimic cardiovascular effects of exercise or something like that. That's because the given dose, if you're just doing 20 or 30 minutes, it's It's not going to be the same. Your heart rate doesn't go up as much. You don't feel as hot because the temperature is not as hot. Now, you will sweat based on a different mechanism. But as far as my take of the literature, it's pretty clear to me that infrared saunas, if you want it to mimic the cardiovascular exercise response, you might have to double that.

Duration. Yeah.

Rather than spending 20 minutes in a 175-degrees, 180-degrees sauna, you're going to spend 40 minutes. You're giving up your time if that's the sauna that you either have or enjoy. Because if you do, and I've been in infrared saunas many times, if you stay in long enough, you get that. You feel hot and you feel that heart rate going up just like you do when you're in a hot sauna. It just takes a lot longer. Now, I know you've had Dr. Ashley Mason on your podcast. She's been on my podcast as well.

We collaborate. Isn't she awesome?

She's awesome. Just love her. She's awesome. We collaborate on a variety sauna studies. She wears a lot of hats. Her data, looking at... She's a psychologist by training, and she looks at depression, and she's looking at depression as an endpoint in terms of these infrared saunas. She's looking at core body temperature increases. To people, their core body temperature is going up by almost two degrees. In that case, she's got them in infrared sauna for 85 minutes. They're in there a long time. They are getting hot. She'll talk about it. She's got assistants that are cooling them down on their head because it's a head out infrared sauna. It's basically like a bed. Anyways, that's the whole other area looking at the effects on mental health. This actually stems from her mentor, Dr. Charles Raison, who I had on the podcast many years ago. He did this really phenomenal pilot study looking at... It was funny. It's called hyperthermia. You're inducing hyperthermia. It's this funny chamber where it's increasing your core body temperature. But Ashley's not using that anymore. She's established the heat bed as It's a safe way.

What do you think is the role of the head being hot? When I am in our sauna, which is a dry sauna, and I'll run it pretty hot, at least 190. Again, part of it is I don't want to be in there for more than 20 minutes because time is tight. Time is my most precious commodity. I'd rather do 190 to 200 for 20 minutes than go longer. But I will tell you, the most discomfort is in my head. Now, of course, part of that is I'm sitting on the top bench. Temperature is hottest at the top. I think my head is exposed to more heat than my torso just based on that difference. But is there harm or benefit, or do we know anything that's happening from any of these other metabolic parameters?

To answer that question, it'll take me in a whole other direction. Should I go there right now, or should I finish? No, finish because I wanted to- I'll finish and then go there. All right. Basically, the only point I was getting at was the pioneering study where people with major depressive disorder were exposed to this device where they're heating up their core body temperature by about two degrees. They had an antidepressant effect that lasted six months compared to a Sham control, which was also heating people up, not- Single treatment? Single treatment. Now, Ashley has gone out and she's done 4-8 treatments, depending on the person, whether or not they completed the whole study. She didn't have a Sham control, but she's got just phenomenal- How do you Sham control that? What he did in his study was he had the same device that just got people a little bit warm, enough where they were thinking they were getting the active treatment, but it was not- Didn't hit the threshold. Yeah, raising their core body temperature by two. It was a phenomenal study. This is, by the way, Peter, what got me interested in the sauna back in 2008, when I started doing it every day.

I lived across the street from OMCA. I was going into the sauna in the morning. It was freezing in Tennessee. I was going in the sauna in the morning before I would go into the lab to do my experiments. I was going every single morning and staying in a long time because I was like, go hard, go home, thing. I love the heat. It was incredible the effect it was having on my mental health and my ability to deal with stress and anxiety. So much that I was like, this is insane. What's going on? Nothing has changed other than I'm going to the sauna every day before I go and do all my failed experiments. That's what got me into the whole sauna was actually the effect on my mental health. It's fun to go full circle and team up with Ashley on some of this research as well. She's amazing, by the way. She's got some new studies coming out in this whole field of sauna depression. I think just she's opening the door. That said, the effect on the head. If you think about hot tubs, Jacuzis, we're all sitting with our head out as well.

We're in there, and it's a It's a good question because I agree with you. When I'm in a hot sauna and I'm also on the top and it's the same deal, I want to get out in 20 minutes, if I stay in too long, I will get a headache. I know my threshold now. I know the temperature and the duration and the amount of water I know all those variables.

Isn't it amazing how much water you can drink in a sauna? I know. I worry I'm going to get hyponatremia. I'm like, You got to slow this down.

The interesting thing is that talking about dementia risk, I talked about heat shock proteins, and I went off on this tangent. Sorry. But the heat shock proteins, what they do is they prevent proteins from misfolding and forming aggregates. Obviously, when you're getting into a hot sauna, you are denaturing some proteins. So your heat shock proteins are a stress response that's activated to help with the proper folding of those proteins that were denatured somewhat from the heat that you were exposing yourself to. Well, it turns out the heat shock proteins stay active for a long time, and so they end up having this effect where you're now just improving the folding of proteins in general, even after you're out of the hot sauna. There's a lot of animal studies that have been done. I did a lot of studies in worms many, many years ago where you can take amyloid beta 42, inject it into a worm muscle tissue, and then activate heat shock proteins, and it prevents the aggregation, and it prevents the muscle paralysis that occurs in these worms. Animal studies have been done looking at amyloid beta and heat shock proteins and Alzheimer's disease.

Again, it's having a protective effect. Now, is that the whole story We know the cardiovascular effects are also important for brain health, in my opinion. You know the data coming out of Dr. Yari Laucunin's lab showing that dementia and Alzheimer's disease risk is 66% lower in people that are using this on a 4-7 times per week versus just one time a week, of course.

That was at 179 degrees or greater for 20 minutes or greater, right?

Yeah, like 175 or 179, exactly, for 20 minutes. Now, here's where your question comes in, and that is, what about the head? There was another study out of Finland. It was not Yari's lab. It was another professor that I'm not aware of. But this study looked at sauna use and dementia risk, and then it stratified the data based on temperature. It was protective, again. People that are using the sauna, again, they're getting a protective effect against dementia. But when people were going extreme, so if they're going above 200 degrees Fahrenheit, and on average, it was like if they're getting to like 212. People do this, by the way. This is like you can go on Instagram and see it's not an uncommon thing. Their dementia risk was increased with that temperature where it was really hot. My concern is the head at that high of a temperature.

I've started wearing one of those- Sauna hats? The sauna hats. I don't know why it works. Do you? It's not logical to me why it's helping rather.

I don't know. It does seem to help. I mean, it shield probably some of the heat that you're being exposed to, right?

Yeah, I suppose. But the fact that that's a net benefit because it's also got to be preventing you from dissipating heat. Clearly, what it's preventing coming in is it exceeds with it, but it makes such a difference. I've also dialed mine down a little bit. I used to be consistently going to at least 200, and now I'm like, You know what? 185 to 190 is good enough.

I do 180.

My wife is going to be very happy if we dial it down to 180. She seems more sensitive to the heat than I am.

I'm more sensitive to the heat than my husband is as well. I wonder if there's some sex thing where, yeah, it's definitely like I'm more sensitive to it.

But this is important. You really think that we could even dial it to 180? Absolutely. And just totally get the same benefit.

The data is showing that.

Yeah, I know. You know me. More is better.

More is better. I'm not just you. It's the go hard, go home. But I do think we're talking about a type of stress here, right?

Yeah, and you have to get it hormetically correct.

Exactly. I don't know that the 212, and I hope people that are out there doing the 212 are listening to this because it's too hot. There's no need for it. There's no evidence you're getting added benefit. If anything, there's-Potential risk that you're getting. Exactly. Potential risk downside. That's just one study. But it's enough to make me go, There's no data showing we We need that, so why are we doing that?

Rhonda, I know you got to go, but I want to end with just one question and topic, which is, what year did you launch your podcast?

I launched it in-14? 2014.

Here we are. We're 11 years in. You are the Ogie in this space. You have an incredible podcast. Are you still enjoying it? And what are you most excited about?

I love doing the podcast. I don't do it every week like some people. I like to find the guests that I'm really interested in learning from. What I love the most is I've always learned more from the conversations I would have with my colleagues or professors than I would from reading a paper. Now I get to do that for a living where I'm just having these superstars on my podcast, and they get to learn so much. I read their papers first, but I also learn so much from the conversation, and people get to benefit from it. I mean, it's so rewarding. I get to scratch my own itch, and then I also get to help people.

I just want make sure that everybody listening understands your place in the podcast landscape, which is I've talked about one of my favorite podcasts, probably my favorite podcast, or one of my two favorite podcasts in the world is called Acquired. Acquired is a podcast about companies, great companies, and what makes them great. The hosts of that, Ben Gilbert and David Rosenthal, they only put out one a month on average. But the reason is the amount of work that they have to put into the preparation is insane. I've gotten to know Ben, especially. Ben is putting at least 120 hours of preparation into each podcast, and therefore, you can only do one a month. And it shows. So in many ways, I think of you as the acquired podcast version in our space, which is just the breadth and the depth of what you're doing is awesome. It's such a treat. And it's always quality over quantity. And yeah, I'm sure if you could put out one a week, you would. But the reality is you wouldn't be able to put in the quality if you were trying to bang one of these things out a week.

Anyway, I'm glad to hear you're still loving it. And it's hard to believe how fast time has gone. I remember being on your podcast podcast in 2014, so that's insane.

You were one of the first 10 guests.

I knew what a podcast was because Tim Farris had had me on his, but it was like, I didn't really understand what this was. I was like, I wonder, why does she want to talk to me? It seems random, but look at how much it's evolved.

I know. Well, thank you for the kind words, and I feel the same about your podcast. When I'm looking for information that I know I can trust, it's always like I'm like, Peter. What's Peter? Peter is someone that I've always been able to trust Just for being rigorous. Like you said, if something changes, then you change. I respect that.

Well, Rhonda, this has been super interesting. As is always the case, there were about 80% more things we were supposed to talk about today. But I'm really glad that we got to the topics we talked about. I think the protein question, the creatine question, and this nuance around temperature are all things that matter to everybody. In two of the three cases, I learned a lot. Obviously, on the protein side, it was more about you and I trying to set the record straight. This creatine stuff is new. It's going to change what I do. Also, you've already made a change to what I'm going to do in the sauna. So thanks again. This was awesome.

Thanks, Peter, for having me on. I really appreciate it.

Thank you for listening to this week's episode of The Drive. Head over to petereateiamd. Com/shownotes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram, and Twitter, all with the handle Peter Atea, MD. You can also leave us view on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional health care services, including the giving of medical advice. No Dr. Patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their health care professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit petereatea. Com/about, where I keep an up to date and active list of all disclosures.