#076 Building Muscle with Resistance Exercise and Reassessing Protein Intake | Stuart Phillips, PhD

Sarcopenia accelerates during disuse events - older adults lose muscle faster and recover slower

Muscle loss from disuse is far worse in older adults who can't bounce back like younger people. Resistance training builds a buffer.

"But it must speak then to the quality of the muscle you have and your brain's ability to be able to talk to muscle and get you to do things. So as much as we can do to try and slow that, that would be beneficial as we get into our older age, for sure. Yeah. And I definitely want to get into all that stuff, you know, how we can counter sarcopenia and loss of muscle mass. Building up of the muscle reserves, not like that's something I've heard you talk about, or, you know, it's something that's common knowledge to some degree. What does that mean? And, like, is it, you know, really important to do that before a certain age? And if you don't do that, can you still start later in life? Yeah. Yeah, great question. I mean, I think the parallel that most people are most familiar with that we can sort of pick on and say, you know, women in particular are told that we can build bone mass up until probably about 30. Men, it's about the same. That when women head towards the menopausal transition, that they're definitely going to lose bone mass. You want to start at a higher level as possible. I mean, everybody after the menopausal transition loses bone at about the same rate. So you really would like to be on a higher plateau before you get there. I think the concept is entirely similar with muscle. The good news is that probably even past your 30s into your 40s, 60s, probably even into your 70s, we can still gain a little bit of muscle. We can definitely gain strength by concerted resistance exercise usually. So you probably have a much bigger window to accumulate the muscle that you have, but it's the same concept. You'd like to go into older age when you're beginning to lose muscle at a higher level because then you're starting to decline from a higher plateau. So it's a similar concept. I don't know that we know exactly how much and when, but there are even studies in nonagenarians, you know, people in their 90s lifting weights, and they can get stronger. Now, gaining muscle, not so much, but they get function back. So there's some adaptability left in the system in a muscle sense that isn't there with bones, for example. And at the end of the day, as you're mentioning, you know, being able to get up out of your chair and, like, these sorts of important little, like, everyday activities that we take for granted when we're younger can make a difference when you're older and you, like, fall and break a hip and then you kind of go into this downward spiral. So strength does make a difference with that, right? Like just having, even if you're not gaining muscle mass, like being able to have the strength to do that. Yeah, absolutely. I mean, I think that that's maybe a little bit overstated with the importance of muscle mass. Not that it's not important, but the function and the outcome, so the strength and the power is really the key point. Even something as simple as walking speed, or what we call normal gait speed. And the example I like to give is to say, you're standing at an intersection, the walk signal comes on, and there's a certain distance you've got to cross in a certain amount of time, so you need a certain gait speed. And not that the motorist hopefully wouldn't stop, but you're under pressure to make it across an intersection, let's say. It's important. And we know fully that once you get to a certain level of strength, your gait speed drops. It becomes more difficult to do activities of daily living. And then you're looking at full-time institutionalized care. Right. Quality of life going down. And it kind of goes back to that concept of improving health span, right? You know, basically being able to delay the onset of these age-related diseases and diseases that hit us later in life in any possible way that we can, even if we don't necessarily live much, much longer. But in some cases, delaying those diseases, you might get a year or two, right? I mean... Yeah. I mean, I think it's not trite to say, but, you know, everybody said, well, what's exercise going to give you? And we do have, and again, it's observational data, of course, that, you know, once you hit that sort of 150 minutes of moderate to vigorous, which are, okay, that's the guidelines. And I think you maintain your strength. And so make sure you do those two days of strengthening exercises a week. We get, let's say, we get on average when you look at population data, about four extra years of life. So I think most people would take that. If that were a pill, we, you know, I wouldn't be sitting here. I'd be Skyping in from Tahiti or something. And most people obviously realize then that your health span that's associated with that is longer as well. So it's, it's time in your life that's longer, but it's time in your life that is spent in good health. And for most people, that's a better quality of life. Absolutely. So let's talk about some of the major signals and inputs that regulate muscle protein synthesis, which I guess we can talk about how much that correlates with muscle mass and strength. So you've published...I mean, let's first talk about recommended daily allowances for protein intake for adults in the United States and Canada. It's about 0.8 grams of protein per kilogram body weight. Correct. And I don't know what people are actually consuming. Maybe you can shed some light onto that, what they're actually consuming. But also, like, what you're...I know you have thoughts, because you've published them, on whether or not it's scientifically sound, that number specifically. Yeah, yeah. So I mean, one of the things that precursors like to start off with is to say, people say, you know, how is protein different than everything else that we eat, and what does it do? And so I often explain to people that carbohydrates and fats, that's fuel. You put that in and you burn it or we store it. And unfortunately, we're really good at doing that. But protein is something that when you ingest it, your body has to use it. And there's not like a little sort of place that you can store away the building blocks of protein, which are amino acids, and kind of use them for later. Although your muscle is sort of a reservoir of that. So it does turn over a little bit. And then so when we think about it from a daily recommended intake or what we call the recommended dietary allowance, it's the amount of protein that you need to ingest to replace all of the protein and amino acids that your body loses. And most of it is lost in urine as urea. And I say to people is I've stopped trying to fight too much against this because I would actually be happy if they just changed the name from recommended dietary allowance to minimal dietary intake. So first, I don't think it should be recommended because it's too low. And I think you should be allowed to eat more. So 0.8, I think, is to me, that's the sort of bottom level buy-in. That's where you need to start and then build up from there. So most of the data that we have, and it's not ours, there's lots of other people have contributed to this as well, suggest that a minimum might be closer to about 1.2 grams per kilogram of body weight per day. And, you know, athletes and even older people could probably benefit even from going up from that level up to about 1.6. At a certain point, I don't think you can put too much protein back into the system and the system would hang on to it. So every species has evolved a way of getting rid of extra protein. Fish, it's ammonia. Birds, it's uric acid. Mammals, it's urea. So there's an upward limit. But most people, depending on what surveys you look at, when they're younger and even middle-aged are probably doing okay in terms of protein. So I'll put hand on heart and say probably not a big issue. When you get a little older, people's appetite goes down. People tend to gravitate towards different ways of eating. And protein actually becomes a much smaller percentage of their diet. So at the time when I think you need more protein and you want to support muscle mass and lean mass as you age, most people's protein intake is actually going down to levels where it becomes limiting to the amount of muscle that they can hang on to. So that I think is an important sort of distinction between let's aim at the minimum and let's go into what we call a more optimal protein intake range. And I don't know where and at what age that begins, but I think it's an important consideration as most of us, myself included, transition towards, you know, I'm looking at the rest of my life and thinking I want to be in as better as best health as I can. And so I have to be a little bit more cognizant about the protein that I eat. What went into your determining 1.2 grams per kilogram body weight? So you're saying most young adults are consuming that probably. And then also, like, you know, I guess, you know, talking about the audience, like, are we talking about, like, to people that are in, you know, a big caloric excess? Well, they're probably already getting that protein, right? I mean, like, if they're in a huge excess of, you know, eating more calories, they're probably getting more protein and everything else. But, you know, so, like, is it relevant for, you know, every age or maybe people that are really physically active, like you said, go up a little more? So why 1.2? What was the science behind that? Dr. Yeah. So the original studies that led to the derivation of the recommended dietary allowance are what we call nitrogen balance. And as the name implies, it's measuring all the nitrogen or protein that goes into our body and collecting everything that comes out. So wonderful, delightful studies to do. Those studies we've known for a long time are problematic because of incomplete collection, overestimation, et cetera, of losses. So one of the things that we do know is that the closer you get to your requirement, your body actually gets much more efficient at utilizing protein. And that's not really taken into account in the way people have modeled that data. So without going too deep into the weeds, let's just say that there are alternative approaches using stable isotopes that have consistently shown that people actually need, when I say need, to maintain the balance that we talk about higher intakes. And so that's the 1.2. So it's not that 0.8 really does it for a lot of people. We need to come up to 1.2. And then from 1.2 and above, we're talking about optimal intakes. And I think the example, the one that people can maybe relate to a little bit is that up until probably about 20, 25 years ago, we aimed at a vitamin C intake that prevented scurvy. And that was good because who wants scurvy, right? But then we've done some science and not me, but obviously lots of other people to show that intakes above the vitamin C intake that prevented scurvy were actually associated with health benefits. And so we make that recommendation. We haven't done that for protein. We're still aiming at the prevention of deficiency as opposed to the optimization of processes that are important. And there's still a lot of people that push back against my viewpoints, and, you know, I'll take the heat. I think what hasn't been considered is this maintenance of muscle and mobility as we age that is, in part, driven by protein intake. I mean, the other half is we can't get away without talking about exercise, right? So that's the other side of the equation. Right. Well, let's talk a little bit about...so, the protein intake, and you're talking about people giving pushback. You know, there definitely are animal studies that have looked at, you know, caloric restriction and protein restriction and its effect on how lab rodents live and how healthy they live. I just, I think that as you and I have talked off camera, there's a lot of different types of people that are in different life stages. We've got obese people, like sedentary, that could probably benefit from caloric restriction. We've got young, healthy, physically active people that are probably needing more protein intake. We've got the older people that are battling sarcopenia that probably need more protein intake. And then we have the whole fasting community. So I mean, it's like I've had a lot of fasting experts on the podcast, as you know, and I think a better job that needs to be done is basically just talking about the audience, talking about, okay, who are we speaking to here with this specific thing we're talking about? Because that's important. There's different people in different stages of life. And then I think also with some of the protein restriction as well, very similar. And I've listened to some of the things that you've talked about with extrapolating data from lab animals, specifically on caloric restriction and dietary restriction, protein restriction to humans, may be a little murky because of something called this disuse and disease that humans are just so susceptible to. So can you talk a little bit about that? Because it makes so much sense. Dr. Yeah. I mean, the writer's statement, I think, and the disclaimer right at the start is to say tremendous amount of respect for the science of the people that do the studies around caloric restriction, protein restriction, et cetera. Most of it is done, as you mentioned, in lab animals, mostly small rodents, so usually mice or rats sometimes. And I think one of the things that's important to point out is when we've compared primates head to head, so this is in caloric restriction, arguably the most robust model of survival, extending lifespan, the data is actually conflicting. It's only been done, obviously, in two different locations. And so if you were a primate in one location, you did better than primates in the other. But the net result was it actually didn't extend lifespan. So that sort of makes you think, okay, maybe it's not as clear-cut as you might think. Obviously, small rodents, they're mammals, so the extrapolation to us is often done. Drug companies do it all the time, I understand. I think the thing that I focus on the most is around there's a caged animal that lives in a very controlled environment, and there is no fluct in food. It's sort of held it here or here because it's given or taken away from the animal. So, you know, choice is taken away from the animal. The human beings are notoriously, sometimes great, sometimes not so much at making. And, you know, these animals aren't exposed to a lot of the same stressors. So one of the concepts that we, and it was something in reading, a good friend of mine, Doug Padden-Jones, who sadly passed away really early in his life, pointed out at these catabolic crises that we have. And for him, it meant a period of hospitalization. And during this event, the de facto treatment in hospital is you go into bed rest. And we've known for years that putting people in bed rest, and you can ask any clinician, it's a bad situation. You're not using your muscles. You become instantly sedentary, obviously. And it would exacerbate a lot of other issues if you went into bed rest with type 2 diabetes, you were overweight, you, et cetera, et cetera. So these events, you can appreciate bed rest and a catabolic crisis if you've got a hospital event is, yeah, that's going to be bad. I get that. So we sort of said, well, dial it back a little bit. Maybe you get flu and you're an older person. You get some respiratory distress. You go into hospital for a few days. You're on oxygen, but now you're fine to be released from the hospital, but you go home and convalesce for two weeks. So this is a disuse event, relatively speaking, but you're okay, but you sit around for two weeks. And we think as you get older, even those types of events are a disuse event that we think precipitates an issue. And I was fond of saying that, well, you know, this happens every year in, well, it happens everywhere because people get the flu. And I said, but there's maybe a uniquely, if not Canadian, but northern U.S. phenomenon that when it's freezing cold outside, you also, as an older person, you don't go outside. You don't want to shovel your snow. You could slip. You could, you know, so, and clinicians would say, yeah, but, you know, how often does that happen? Then COVID comes along. And I said, happens a lot."

Two mTOR complexes: one responds to nutrients, the other to exercise

mTOR has two complexes: one responds to nutrients, the other to exercise. Exercise-driven mTOR uniquely drives protein synthesis.

"There are some thoughts now that there are actually two complexes of mTOR, one that's sensitive to nutrients, one that's sensitive to nutrients, one that's actually more sensitive to exercise. And one function is a little bit different than the other, but the ultimate culmination is that the downstream signals after you've stimulated mTOR are to turn on protein synthesis and all of the regenerative or anabolic processes to repair or recover from any stress that's been exposed. So yeah, it's essentially important protein. We study it a lot. We're by no means experts in it. There are people that are far better at it than I am. Yeah. So inhibiting the one like mTORC1, which is the nutrient-sensitive complex with something like rapamycin, could affect muscle protein synthesis, but not...because there's also mTORC2 activity going on, if a person is resistance training, maybe does it...is it not as big of a deal, or is it still does affect it? Yeah. I mean, I think, like I said, the benefits of the resistance training probably through mTORC2 are like this. You still get the protein synthetic response. With mTORC1, I mean, that's where the sort of thinner layer of the nutrient-added stimulation goes on top of resistance training. So as you say, one's sensitive to rapamycin, the other one actually isn't. So the more we uncover with this, the more we realize we probably, 10 years ago, we thought we had it figured out, no, we're not even close. And so now we're beginning to understand that mechanical stress from exercise is rooted through a different process than nutrient stimulation of protein synthesis. So maybe that's the underpinning mechanism why a lot of people talk about restricting protein and not wanting to turn on the overly or overly turn on the anabolic side of things because uncontrolled growth and, because uncontrolled growth and, well, you know, at cell level, that's cancer. But as I point out to people, you know, persistent exercise also activates mTOR on an almost chronic basis if you exercise every day. And now we're like, well, actually, it's signaling through a different process. So maybe that's why. It's beneficial. And this one, if it's chronically turned up, is not so good. Yeah. And it also goes back to some of the observational data we were talking about also a couple hours ago or whenever it was when you're looking at protein intake, specifically animal protein versus plant protein. And animal protein, as you pointed out, is higher in essential amino acids, including leucine. And so you look at these all-cause mortalities and these cancer-related mortalities, and there is definitely conflicting data for sure. But there is an overall...like, there's a lot of studies showing that there's a lower all-cause mortality and a lower cancer-related mortality in people that consume plant proteins. However, when you start to look at the largest observational studies that have been done, those studies that have looked for any, like, unhealthy lifestyle factors or confounding factors have found that, oh, actually, people that have no unhealthy lifestyle factors, so they're not obese, not sedentary, not smoking, not excessively drinking alcohol, they have a similar all-cause mortality as a plant-eating person. So, you know, again, it goes down to that, okay, well, maybe if someone is obese and smoking or sedentary, before you start eating a lot of protein and worrying about that, like, let's get rid of those unhealthy lifestyle factors, right? Let's get physically active. Let's lose some weight, some fat. And then, you know, then things can kind of fall into place. So... I couldn't agree more. I mean, I think in sort of the broad checklist and people say, you know, so what are you doing to age well? And I said, well, I'm trying to stay at a body weight that's, you know, not excessive. I weigh more now than I did when I was 13, 14, no kidding, more than I did when I was 23, 24, but not much more. I'm physically active. I pay attention to what I eat 80% of the time. And people say, well, what about the other 20%? I said, that's why I exercise, so I can indulge myself 20% of the time. I don't need a vegan diet. I don't need a vegetarian diet, but I eat less meat, particularly red meat than I used to. I eat more fish. I don't eat as many, you know, unrefined, or excuse me, refined carbohydrates. I don't really have a sweet tooth, so I was kind of lucky in that way, so I don't feel compelled. I'm weak in the presence of chocolate, you know, so, but maybe that's my one indulgence, but I don't smoke, never have. I don't drink as much as I used to, you know, all of those things, and you're going check, check, check, check, and then people go, well, what about intermittent fasting? And I'm like, you know what, and again, it's my, this is the analogy. I love this is to, you dip the water or you dip the cloth in the water and you, you know, the first ring is like, you get a lot of water out. I'm like, that's maintaining your, your, your body weight. I'm like, the second one is physical activity. The third one is watch what you eat. The fourth one is, you know, and then you could add subtle nuance things more on that. But now you're, you know, it's only little drops that are coming out of the cloth. That's where I think a lot of the finer details, the vegan versus omnivorous diet, if you're judicious about how you plan your omnivorous diet, can make a difference. Yeah, if you're a smoker, that's a great thing to give up because that's a bona fide, a shortened lifespan, poor quality of life, etc. But I understand the power of addiction, and particularly if you started early, which is when most people take it up, man, it's a tough one to break. So... Lose the weight, physically active. I think what you said is pretty fair. Yeah, the most important thing is... Some broad strokes. And then the little drops that can come out. Hormones. Growth hormone, testosterone, getting into the sex hormones. I was quite surprised by, you know, some of the data coming out of your lab that showed... Maybe you can explain it, because you'll explain it better than I do, but, you know, looking at what effect, for example, growth hormone has on muscle protein synthesis. Yeah, yeah. So this started in, you know, to give you the origins or the genesis of this story. I was early in my faculty appointment, and we were doing these studies where we were infusing people with labeled amino acids to measure the rate of muscle protein synthesis. We were measuring the incorporation of these amino acids, and we had people exercising. These were mostly young men. Freely admit that. We're making a push to do younger women and older women and middle-aged women, perimenopausal women. So stay tuned. It's coming. And we would send it in for publication. And they said, you haven't measured testosterone growth hormone or insulin-like growth factor. And they go up after exercise. And they're driving this protein synthetic response. And my training is as a biochemist. I'm not an exercise physio. I'm a varsity athlete, so pairing the two seemed logical to me. And I'd actually worked with some people that were pretty good with steroid biochemistry. And my understanding was that steroid hormones, testosterone, that sort of thing, slid across membranes, bound to a receptor. Receptor went into the nucleus, modified the expression of genes. And that takes a long time. That's not a transitory, you know, testosterone's up, they do this, and 15 minutes later, it's back down. And growth hormone, the same thing. So we thought, you know, we need to test this. We either need to show that those hormones are important or they're not. And so that's why we don't think we need to measure them. And it's a journey that it's taken us, you know, 20 years, probably about four PhD students, a couple of good postdocs. So it's been a good one. Lots of people have chipped in. And we've tried very, very hard to show that those hormones have an anabolic effect. And we've never been able to see it. And we've manipulated all kinds of experimental conditions. And we just don't see an impact. And I think the most damning evidence against testosterone is a big driver of muscle protein synthesis is to say, you know, if you take men and women and agree, like, men start out with more muscle mass than women, and you resistance train them. And this is a meta-analysis now. A guy named Brandon Roberts did this one. And you resistance train them. Relative to what they started with, everybody goes up the same amount. Women get the same amount of muscle growth as men do, but they had less muscle to start with because, you know, boys and girls are like this. Puberty happens. Boys become men, man-ish."

Some inflammation is needed for muscle growth - chronic suppression with NSAIDs may backfire

Some acute inflammation is needed for muscle growth. Chronically suppressing it with NSAIDs may impair muscle adaptation in older adults.

"So if you keep chronically suppressing inflammatory responses in younger people even, I don't think you get a full adaptation. So some inflammation, good and necessary."