Rhonda Patrick: Hey everyone, I'm super excited to be sitting across the table from Dr. Andy Galpin, who is the director of the Human Performance Center at Parker University. Andy and I have been corresponding for at least the last 10 years. I'm pretty pumped to have this conversation. He is an expert in muscle physiology, but also has published a wide range of, I would say, exercise physiology-related topics from, you know, muscle health to nutrition to recovery. He also coaches athletes, Olympians, MMA fighters, just all around got a lot of experience and the science behind it. So I'm really excited to have this conversation with you today, Andy. I mean, you and I have talked about, you know, a lot of things via, you know, X and Twitter at the time. I think email as well. So thank you so much for coming on the show.

Andy Galpin: It's just, I can't even explain how much of an honor and a pleasure this is. I've been telling you for a long time now how stoked I am about this, and my wife is tired of hearing of it, so I'm finally excited to get here and do it.

Rhonda Patrick: Well, today it's kind of interesting because, you know, you've got this vast publication history in muscle biology and exercise physiology, but I'm kind of taking you in a direction where you've also published and you have a lot of knowledge regarding nutrition, supplements, recovery. I'm super interested in the role of those in helping people sort of meet their fitness goals. And when it comes to nutrition, I mean, this is obviously a field that's constantly, you know, there's no agreement ever, whether we're talking about performance or longevity.

Andy Galpin: Sure.

Rhonda Patrick: But, you know, there's a growing number of athletes and people that are like myself, which are, I would say, committed exercisers, that I'm very interested in health, not as much in performance, although I'm becoming a lot more interested in performance these days. But I'm interested in longevity, for sure. I mean, that's my primary interest. And so there's people kind of trying to figure out what kind of diet they could, you know, what kind of diet they could eat to sort of meet their performance and longevity goals, if that's even possible. Is that something that you've thought about?

Andy Galpin: Yeah, I get the question of performance versus longevity or health or nutrition a lot. And I think, as you've done so well over your career, there are tenets that are going to agree and then there's going to be distension. And so I think it's easiest maybe to frame this as what are the flags we can put on both sides of this equation? Known obvious yeses and obvious noes, right? So if you want to live your longest, healthiest life, number one, we're all going to agree on probably five, seven, maybe eight different things. And if you were to look... I'll just do it this way. If I said, okay, great, because we deal with these clients. I deal with high-performance athletes, as you mentioned, and we have a lot of our clients that are like you. They're not athletes, never were, do not care, but they're wanting to live their longest, healthiest life. And if I threw their diets in front of you, I'd be stunned if you could tell me which one was for which person. I don't think you'd have any chance, right? So you'd say, what's that going to look like? We're going to center around protein, right? You've talked about that endlessly. It's going to be high and high quality. We're going to have a lot of variety of foods. We're going to have a lot of variety of colors. Turns out micronutrients, vitamins, and minerals are pretty important, right? Like your entire career. We're going to have some attention paid to fiber. Caloric intake will be managed. We're going to distribute carbohydrates and fat in some way that helps them hit their needs and goals and personal preferences. We could go down the list. But the easiest way to think about it is, how much overlap is there? Almost all. What are the small differences between these performance and longevity goals? Well, depends on what type of performance. So we're talking about a lot of caloric expenditure. Are we talking about a power event? Then, yeah, we're going to find some differences. And we can chop that up all day if you want to know exact numbers and hours. But the reality of it is, both of those people, performance, longevity, you have to manage calories one way or the other. You have to do all the other things. It's not that different. You can make some arguments of maybe you can get away with certain things. If you're not interested in performance, you can do some different things with food timing, food frequency. You can play with some different stuff where you wouldn't want to do that with a high-performance athlete. So there's a lot of fun differences with those things. But at the highest level for the average person, if you're eating like a high-performance athlete, for the most part, you're also eating for longevity. Only big fundamental difference there might be caloric balance. That's the top layer. But other than that, it's pretty similar.

Rhonda Patrick: I was kind of thinking that was going to be your answer. I'm very interested in the intermittent fasting, time-restricted eating, training while you're fasted, depending on the type of training, because it's something that I do for certain types of training. You like to train fasted.

Andy Galpin: Well, I like to train fasted if I'm going for a 30-minute run, zone 2 kind of run. And the reason I do that is because, I mean, this was years ago, I read a meta-analysis, and maybe I would love to hear your updates on the literature because I know that you've been keeping up with it. But there was a meta-analysis looking at people that were training fasted, and if they were doing endurance type of aerobic exercise training, and they trained, they were training, it was like less than 60 minutes. It was like less than an hour, right? And this is like a zone 2 kind of below the lactate threshold type of training. Then they had better adaptations in mitochondria, mitochondrial enzymes, obviously like fatty acids being oxidized. So whereas if they trained when they were fed, again, it was less than an hour, some of those adaptations were blunted somewhat. And for me, it was like, oh, well, I kind of want those adaptations. So I do like to train a little bit fasted. Now, I don't do hour-long runs anymore. That was like a thing of my past for me. I do my strength training. I do not like to do fasted at all. I have to have like something like a banana. I have to have some glucose or something. So I'd love to get your take on training while fasted.

Rhonda Patrick: Right after that, I'm also dealing with a guy preparing for a 900 mile hike. So that context is important because as I'm answering questions like this, all these avatars are in my head, and I'm thinking, what is true for person one, two, and three, and what is true for the other person who doesn't exercise at all? If something is not consistent across those four, then I have to modify and contextualize the answer. So when it comes to training fasted, great. If you are going for an event like you're talking about, and you feel better when you do it, that matters to me in that particular context more than the physiological benefit, because the physiological benefit is not fake, it's just not huge. So is it more beneficial for your mitochondria? Yes, potentially, but if you look at the amount, it's not that much. Now, if you liked it or didn't care, fine. But if you're like, I hate it, my performance is worse, I don't like it, I don't feel good, then we actually don't do it. And so my first layer answer to all that is, number one, what are you actually performing best in? What are your personal preferences? Are you training in the morning? Are you training in the evening? All these other factors that are now, again, contextualized are my true answer. And I hate to be wishy-washy on that, but that's the most honest answer because I deal with a lot of people with different goals and different scenarios. So the science can lead us in one direction, but the actual layering on top of what would I really recommend a human do, that in this scenario matters more. So if you look at the research very specifically on fasting exercise, always depends on the type of exercise. You mentioned you were really careful about saying, I'm under 60 minutes, right? I'm under 60 minutes. I know you're aware that answer will change. What am I optimizing for? Performance? Am I optimizing for feeling better that day, more focused that day? There's so many different reasons why one would exercise that you have to answer all those questions and figure out, well, what lever am I trying to pull here? So do we ever take somebody and say, hey, you need to start doing your endurance work in the morning, fasted? I can't think of many times we've ever done that. But if somebody shows up with that, we don't have any reason. We're not going to pull them off it either.

Rhonda Patrick: What if someone says, I'm interested in fat adaptation, I'm interested in mitochondrial health, and I'm not an endurance athlete. I'm just, you know, these are my recovery days, I do strength training on other days, these are my recovery days, so to speak, in a way. Then would you still kind of, what are your thoughts on that? So you mentioned mito adaptations aren't, it's not, it's a subtle difference. But what about lipolysis? Like what about, you know,

Andy Galpin: Yeah, so the way that we would frame this is we need more information on them to determine whether or not that's going to actually matter for them. So if they're saying, okay, I want to enhance fat burning, I want to enhance oxidative capacity, great. Well, we actually need to look at their capacity for metabolic flexibility. We need to test that. I need to see that number, right? If you're just saying you want more, I'm going to say more from where? Like, where are you currently at? I don't know. Well, then we don't know if we have anything to actually gain here. So we could do that intervention, and I don't know if it would do anything for you. If you're already pegged on that, if your mitochondria are already functioning very high, if your ability to utilize fuel independent of food is strong, then we're not going to get anything from that. If you're really weak in that area, then we would get something from it. So our first answer is data, right? We have to run some objective tests. If you don't want to do that or can't do that, you want to give that a try, sure. Like, fine, it's probably not going to hurt much in the short term. So go ahead and do that. So my answer to somebody who asks that question, I want to optimize mitochondria, okay, great. Starting off with fasted cardio is not the place we would go, but we might use it eventually if you can do a whole bunch of stuff, and we could do this objectively. Okay, when you go out and train, how do you feel if you don't eat before? Oh, I feel terrible. Then that's an easy litmus test. There's way more we get into in detail. I wouldn't only ask that question, but that's how we'd actually think about it. So it could be everything from yes to I'm not super worried about it. If they're really, really stoked to do it, I'm probably going to say yes just for that fact alone. But I don't necessarily think you have to do that to have healthy mitochondria, if that's another way to answer the question.

Rhonda Patrick: What about people that are doing strength training, resistance training first thing in the morning, and they don't have a lot of time? They're getting their kids ready for school, it's like they want to feel with something. What's the best option?

Andy Galpin: Personal preference in terms of feeding or not feeding. The literature would be fairly clear here, and I'd say our personal experience would match that. Some people are fine, some people are not. If you want to go just practical recommendations, a banana and a protein shake is super easy, a little bit of yogurt maybe and granola. We have a lot of our athletes that will train in the morning, and that's a really common thing. Some granola, yogurt, maybe honey, maybe some berries, small six to eight ounces, right, really small servings, 300 calories, maybe 50 grams of carbohydrate, some protein, 10 to 30 grams, depending on their physical size. Remember, some of our athletes are 115 pounds, some of them are 350 pounds, so numbers vary. So personal preference, but yeah, the recommendations would be things like that. We don't have too many athletes or clients that we'll intentionally ask them to not eat before they train, like we sort of talked about, but the easy, quick, just get out the door stuff, that's what we're going to lean on, very simple, easy digesting, small amounts of food, probably not as much as your full breakfast, but those things will tend to work pretty well.

Rhonda Patrick: I think athletes are less interested in that, and people that are more interested in body recomposition, they're wanting to lose fat, gain muscle, are more interested in, okay, well, perhaps they're that kind of person that their liver glycogen takes more hours before it depletes, and then it's like, well, if I then eat before my run, then I didn't fully deplete the liver glycogen, so they're not going to be perhaps undergoing lipolysis and oxidizing fatty acids for energy. So what about people that are interested in, that are fit, they're not really athletes, but they're exercisers, they're interested in just sort of fat loss, body recomposition?

Andy Galpin: The acute timeframe pre-, mid-, post-exercise for those people probably doesn't matter that much. It really isn't going to have a huge impact. What will matter is the days and weeks, the total caloric expenditure throughout the day. This person, if you're training in the morning, you probably have at least 24 hours to recover, even if you're training hard every single day. Most of the time, when we get really specific about nutrient timing, it's because a lot of our clientele are training twice or more a day, that's when timing really is critical, whether you're talking about timing of fat, protein, carbohydrates, so when we hear people say things like, oh, timing doesn't matter, for the average person, it's not a huge deal, but for some, it really significantly matters. But what you just described is not. You're talking about the person who is just training once. There's a ton of recovery time. So what you have before the workout doesn't matter a huge amount. Whether you have it immediately post doesn't matter a huge amount. The total in throughout the day. The only caveat is actually what you asked a little bit before, it's personal preference, I don't feel as well. Great, that's the context, it's not the physiology or the biology that's mattering there, it's now personal preference or objective data that says we

or it makes your sleep worse, or it's better for everything. Whatever combination the answer is going to be, I don't really care. But that's the full context people have when they make dietary decisions. So that's what we did. We took people that were very well trained, and we did eight weeks of strength training with them in the lab, supervised, all that. Already, again, previously well trained, men and women, college age, as normal. We did biopsies, we did muscle imaging, we did questionnaires, we did sleep stuff, we did blood, we did a bunch of different things. And ultimately what we wanted to see was, okay, we're going to put them all at the same protein load, and we're going to put them in caloric excess. So hypercaloric, not hypocaloric. We know the answer what happens with TRE if you're trying to lose weight. What happens if somebody actively trying to gain muscle? So that's the very unique twist of this. And it was super interesting. The take-home message was it didn't matter a ton. As long as you hit your numbers, the results were basically the same across both groups. So standard four, five, six feedings a day versus TRE. Now we actually doubled down on the question because we actually made the people train in the TRE group in the morning, and then they had to wait at least an hour before they fueled afterwards. So they trained fasted. They didn't recover with protein or anything like that immediately afterwards, and they stayed in that state until the afternoon. So even despite of that, it didn't significantly compromise muscle growth or performance or really anything else. We saw some subtle differences. The TRE group actually looked like it didn't gain as much body fat because you're going to do that when you go hypercaloric, right? Especially if you're well trained, you want to add muscle, you're going to bring some fat along for the route. I don't know if it was enough of a difference, and I spent a lot of time in that data set. I don't know if that's a real finding, to be honest, or if that was just a little bit of an artifact. The counter to it was as time went on, fatigue got higher in the TRE group. Legs got heavier. Performance in the legs started to decline. Again, so much so would I suggest TRE is going to be bad? No, no, but it was like, okay, I think there's something happening here. I think potentially if we were to change the study design a little bit and give them fuel closer, that would have made it not exactly sure. We would have to run a separate study design for that. If you torture the data a little bit, you might find some subtle differences between the two groups, and they were statistically significant in effect size and all those things there. But looking at it from a real practitioner perspective, my general take-home was it didn't matter a ton. If you're trying to maximize leg strength and maximize leg growth, I probably wouldn't go to 16-8 TRE. But if you have other reasons to do it, you're still going to get gains. They still got stronger. They didn't get as strong. There are some other issues that happen, but either one of them works.

Rhonda Patrick: But do you think, again, if they were a lot, I mean, most people, after they're done strength training, they eat within an hour. Like I immediately am getting protein in me because I just, my body wants it. So do you think that maybe would negate some of the performance deficits that you found?

Andy Galpin: I think it honestly was more of a carbohydrate issue.

Rhonda Patrick: Carbohydrates.

Andy Galpin: Yeah, I think that was the bigger issue because they were going so long without carbohydrates and they were training so hard and they were doing the same workout multiple times per week. I just think over time, we were also progressing them. So they were being tested every time they came in the lab and the training got harder, right? Like traditional progressive overload. I don't think they—I wish we had actually biopsy data for their muscle glycogen levels. But if I had to suspect, I think that that was starting to leak down. And I just think the legs were getting—we would say just getting heavier over time. Like it just wasn't handling the volume because that's actually what happened too. The volume that the TRE group did started to come down at the end. They just couldn't do as much volume as the other group could do.

Rhonda Patrick: At the end of a workout, not like at the end of the eight.

Andy Galpin: No, at the end of the eight weeks. Because we tested them pre, mid, and post.

Rhonda Patrick: When were they working out? Morning or evening?

Andy Galpin: Morning. Yep, they're all working out fasted. They're doing strength training fasted. Yeah. So the bottom line—this study will be published soon, depending on when this comes out, it may already be out any day. I'm stunned it actually hasn't. You can gain muscle on a 16-8 time-restricted eating schedule, even if you're doing the training fasted. There are ways to do 16-8. You can stop eating earlier and not have to be fasted in the morning, right?

Rhonda Patrick: Congratulations. This is great. This is a great study. You sent it to me, I can't wait to read it.

Andy Galpin: Well, so actually, that's super interesting, because when I looked at this, I was like, man, I think that just is the better approach. Maybe if they would have done their fasting in the evening, afternoon—there's a bunch of other arguments we could make that that's better anyways. That would be a really cool follow-up. And I'd be willing to bet they wouldn't have had such indirect markers of fatigue over time. They just didn't have fuel for a really long time. I can also tell you these things behind—and this is like the veil of people that, when you run actual studies, you can make comments about things that aren't in the paper. The people had a really hard time with the carbohydrates. That was the complaint. And so when you had a whole bunch, because some of these people are at 600, 700 grams of carbohydrate a day, and you got to get that in an eight-hour window, GI was just destroyed. A lot of people were like, man, my stomach is just blowing up from 600 grams of carbohydrate. Could you imagine eating 200 grams of carbohydrates, a couple hours later you got another 200, another 200. It was just a lot.

Rhonda Patrick: Was it so high because you were doing this hypercaloric? Because I mean, most people aren't doing that many carbohydrates unless they're like endurance athletes.

Andy Galpin: Yeah, well, we have some big people, right? So if you're 110 kilos and you've got to be hypercaloric and you're at six grams per kilogram body weight, those numbers get high fast. So in order to get there, that stuff got there. Even the protein got a little tough as well. So we didn't see—I wish we would have had more subjective questions in those areas, but I would say it was just hard for those people to hit their numbers. Most of them got there, but they're just like, whoa, I just wish I had another hour. Give me another two hours. Could I get 50 grams of this protein a little bit earlier? That'd make my life so much easier. So I just think from a practical perspective, it was harder for them to follow, it was harder for them to hit their numbers waiting the whole day than to start and hit it in a caloric surplus. So if you're not in a caloric surplus, different equation here. If you're in a caloric deficit, different equation here. But for people that are pre-trained, pretty well-trained, and they're actively trying to get bigger and stronger, it wouldn't be the first approach I would take. But it's still plausible. Clearly it worked. They still got benefits from it. But switching the order I think would be cool.

Rhonda Patrick: Would you say that if they were, let's say they were in a slight caloric deficit, still getting their protein, meeting their protein needs, would they be still gaining muscle, you think?

Andy Galpin: I don't think it would have gained as much. It would have gained some, right? If you look at, like, again, all of Graham's work and a lot of that hypercaloric state stuff, sometimes they gain muscle. It can happen. But can they gain it at the same rate as when you add more calories? I don't think so. And I don't think so because in our particular program, the training program was really aggressive. They were training hard for really well-trained people. I don't think the recovery would be there. I just don't think it would be there.

Rhonda Patrick: When did they stop eating, and how was their sleep affected?

Andy Galpin: So we let them choose their window. So some of them came in and trained at like 7 o'clock in the morning because they want to start their eating window at 10, right? But they're college kids, so most of them trained like 10, 11, 12 o'clock in the morning. And then they would start their eating windows between 1 and 2 o'clock in the afternoon, something like that, depending on if they work or whatever. So we let them shift a little bit. The time domains had to be the same, but we didn't make them start at noon, depending on their life schedule. Sleep didn't really change that much. I wish we would have had some of our newer sleep technology. We could have really objectively looked at it at the time; we just had basic questionnaires. What we did notice is the perceived fatigue and naps increased over time in the TRE group. So again, a little inclination there of saying I think fatigue was setting in more. Some of that didn't land statistically significant, but you start to see multiple things in the same pattern, and you go, all right, if we run a follow-up study there, that might be interesting to focus on.

Rhonda Patrick: Why is it important for people to have carbohydrates before they're doing strength training?

Andy Galpin: You don't have to. If you can get away with it, you're fine. It's not the thing we're super concerned about. Depending on where you're at, if you can get through it, if your total caloric intake throughout the day is fine, if your carbohydrate intake throughout the day is fine, and depending on how often you're strength training, if you're the kind of typical person who's training the same body part on non-consecutive days, then carbohydrate pre-exercise is not a big deal. It's totally fine. You can get away with your strength training. It'd be a personal preference. Again, if you're training, though, the same muscle group on multiple days or multiple times per day, that's when the carbohydrate timing will matter most. You can have it before—generally people feel better with it, performance is usually better, but it's not always.

Rhonda Patrick: Or, or if you're someone that is on more of a hypocaloric diet, if you're trying to lose fat or perhaps maintain your weight, you're kind of really watching your calories, then perhaps you're not having a huge total caloric—totally caloric intake per day—that you might want to have carbohydrates in that.

Andy Galpin: We will generally, as just a high-level rule, try to get more of our calories around training, period, regardless of what we're doing, regardless of what type of training, regardless of the person. As a first-level thing, that's our preference. We want to either do it pre, mid, post. In your example there, if we're trying to bring calories down, we're going to go somewhere else if we can. It doesn't always work that way; people don't always like it. But that is our default position: yeah, we're going to do more calories in and around the training to support it. I want better performance. You perform better, you get better adaptations. That's generally how we look at it.

Rhonda Patrick: What about people that are more endurance-type athletes? They're out running, you know, 10, 15 or more miles, or biking, cycling, biking. What about those individuals?

Andy Galpin: Different equation now, right? So whether you talk about strength training or even endurance training, but as you said earlier, like you're talking sub-60 minutes at kind of a moderate to low intensity, carbohydrate before training for most people is not going to matter that much. Now you're talking about something different: really high-intensity exercise for a prolonged amount and/or moderate exercise for a longer amount, right? So we'll define longer by plus 60 minutes. Now you will very often see performance improvements with carbohydrates. That said, we have some of our people, some of our friends—a good friend of mine that I will never stop giving him the business on this one—Cam Haynes.

Rhonda Patrick: Oh yeah, Cam's great.

Andy Galpin: The worst performance nutrition you could just possibly dream of, right? Like, he will intentionally not eat and drink water and then go run 18 miles, right? And you're just like, what are we doing here, right? I've made the argument, like, I will PR him in every race he's ever done if he would just let me—if he would just follow what I tell him to do. But he refuses. So you can do these things. This is not a matter of it's impossible physiologically, but are you going to get your best out of it? Probably not. Carbohydrates before exercise, probably three or four hours before exercise if possible, if you're trying to maximize performance, generally looking at something in the neighborhood of 50 to 100 grams of carbohydrates. That's a huge plus/minus range there. Three or four hours before, we're generally looking at starches, slower digesting, give it time, not a big spike. Some people we will tinker with 30 minutes before, something in the neighborhood of 50, 60 grams of carbohydrates, maybe a little bit more. Some people, though, deal with a glucose double whammy if you do that, so you've got to be careful. What I mean is, if you take a whole bunch of fast-responding glucose, things that get into your bloodstream really quickly, right before you start exercising, insulin starts pulling glucose down, muscle starts pulling it as well, and so blood glucose actually dips. This is like, I had a banana and honey right before I started my race, and then I got two miles in and I felt like death. Like, okay, you had two mechanisms at the same time that are independent, that are bringing it down, and blood glucose actually dips quite a bit until the liver has a chance to kick in and bring it back to normalized. So you'll feel that response pretty often, so you've got to be really careful with easy-digesting carbohydrates right before the event and depending on how long it's going to last. But those are rough numbers to start with. In the exercise itself, the numbers you're going to see here, somewhere in the neighborhood of 60 grams up to 100 grams of carbohydrate per hour, which is—if you want to maximize performance, you'll see the data will show you like 80 plus, 80 to 100 grams.

Rhonda Patrick: What kind of carbohydrates? We're talking—you don't want that easy stuff, right?

Andy Galpin: No, now you want the fastest possible, because you're in a race, right? You're moving, right? This is when the goos and packs and things hit in, so you're trying to smash it in there as much as you can. I actually just had a guy named Jordy Sullivan, a dietitian in Australia. He was just on my podcast, and he actually coached a guy named Ned Brockman. And Ned did a thousand-mile race on a track, so he ran on a track for a thousand miles. I think it took him like 11 or 12 days, something like that, to finish.

Rhonda Patrick: Did he—I mean, how was—where the sleeping…what was the sleeping—

Andy Galpin: The sleeping situation?

Rhonda Patrick: Sleep on the track, right?

Andy Galpin: Yeah, he would just lay down and crash for a little bit, and then he'd get up and just run again, and he just kept going. Jordy went through the exact details, exactly what he fed him, the amounts, the concentration. And when you get into things like that, when Michael's getting ready for this 900-mile hike thing, 60 to 80 to 100 grams of carbohydrate per hour is awesome in the lab. I put you on a bike and you're in my research facility—those are the numbers that work. But when you cross over into humans, you start getting really tired of goo. You don't want to taste sugary drinks anymore. And so when you get past a couple of hours of exercise, then you actually have to start really paying attention to texture and flavor profile and mouthfeel, because that stuff starts to matter, and you can't hit those numbers. They're just not realistic. So if you're going to try to do something like this, pick your poison in terms of the carbohydrate source—this is the fastest sugars—but if you're going for more than a couple of hours, you've got to really think carefully about, are you sure you're going to like that taste of that for six hours, because you probably won't.

Rhonda Patrick: It's just incredible. I can't believe people do things like that. What about carbohydrate replenishment after a long endurance-type of workout? Do you think that's important to replenish the glycogen stores?

Andy Galpin: Depends on what you had starting with. So did you feed before, or did you not? That is automatically our context. If you fed before, then we don't have to worry about as much directly after. If you're fasted, we've got to worry about more. The other context we have to pay attention to: again, what's our total caloric intake, what's our carbohydrate intake throughout the day, and when are we going to train again? Some of our folks, again, training multiple times per day, we are going to go absolutely out of our way to get 100 grams of carbohydrate post-exercise if it's a hard training session. That's a rough number. Again, that number scales up and down with physical size and caloric expenditure, things like that. If you're going to get on a plane and drive and you're going to do something else for the next two days, carbohydrate post-exercise—the amount doesn't matter—it's not a big deal. You're up against a race of replenishment time. If that matters, you want to, again, look for 100-ish grams of carbohydrate pretty close to finishing. Unlike protein, timing matters. The faster you get that carbohydrate in, the faster you will replenish muscle and liver glycogen. Protein, as you've covered many times, timing, anabolic window, not a big deal at all. But carbohydrates are different. You've got to repeat that performance again soon, faster, more, better. If you've got a lot of time, then your recovery window is plenty; then you're going to be fine.

Rhonda Patrick: Or even if you're just training for a race, right? If you're training like every day, you're probably going to want to get that replenishment in right away.

Andy Galpin: Well, in that case, actually, that's a great point, because it's not only necessarily just about recovering for your next workout, but you actually need to train that system. One mistake people make when they do endurance events like that is they will forget to mimic the race in training. So then when they get into training, they try to do something they haven't done before, and their bodies can freak out. This is when you get a lot of GI distress, when you get a lot of your tapering, and you know, the week before, all of a sudden your performance is down, and you're like, what's going on? Well, you're doing something different now than you were doing the last eight weeks. And so yeah, I would actually strongly encourage you to treat your practice races like your real race. So do your pre-, mid-, post-fueling strategies in preparation for that, so then when you show up, your body's like, yep, this is exactly what we do. This is exactly how we handle people for the Super Bowl, for world championship events, for the Olympics. You try to make those big events where they're so incredibly important and there's so much pressure and stress, that you want to make it feel like a normal practice. This is just what we do. So while most of you aren't going to be on that stage—I get it—when you go run that first 5K, that's still going to be a really, you're going to be really excited, and it's going to feel like that. Your body is going to know, wow, this is something I care about, or you go and you finally get to surf that wave that you've been wanting to do or whatever the thing is.

You've been wanting to go after. The thing you can control the most is making your day feel like you've been training. It's a normal process. This is what we do. Your body is going to know, wow, this is something I care about. Or you go and you finally get to surf that wave that you've been wanting to do, or whatever the thing is, you go on that hunt that you've been wanting to go after. The thing you can control the most is making your day feel like you've been training. It's a normal process. This is what we do. This is

Rhonda Patrick:

Andy Galpin: Everything from, again, I tanked, I bombed, I failed out, to I had my best performance ever. To kind of go back to the original question about eating for longevity versus performance, now we're kind of talking about here. Oh man, we're on question one still.

Rhonda Patrick: Well, no, I just kind of wanted to circle back because if we are talking about someone that is racing, right? They're competing, they're trying to PR, they're, you know, all of those things. Then the carbohydrate sources that they're eating aren't going to be what I'm eating. I'm not going to be, I'm certainly not going to be chugging the goo, but like the fast, like during like intra workout, right? While you're racing or even perhaps like you were saying right before, you know, eating the quick, like the stuff that's going to spike your blood glucose quickly isn't typically stuff that people that are eating for a longevity type of, like my carbohydrate sources are typically vegetables, you know, fruits that have a food fiber matrix. Most of the time, I mean, some fruits can hit your body a little quicker than others, like grapes, for example. But, you know, most of the carbohydrate sources are more complex carbohydrates.

Andy Galpin: Yeah, so fair point. This is that small sliver difference at the end, right? So again, if we were to look at your, we actually have probably, I don't know, five females right now that we're coaching that are plus around your body size. So we'll make just equivalence to you and those individuals. We take both your diets for you and all those different girls that are in different sports. They're going to be almost identical, right? So they're going to be heavily focused on vegetables and starches and fruit and all those things. What would that difference be? Well, okay, some of them post training might do a powdered glucose source. So we might give them a carbohydrate supplement. We might use a Vitargo or something like that, where it's like a scooped carbohydrate where you're probably never having that. You're not having it throughout the day. You're not having it pre and post your workout. You don't need 60 grams of carbohydrate. That's easily that. So that would be different, right? But what are they going to have post workout? I don't know, watermelon. They're going to have things that you're probably eating too. Do we have a little more liberty with them to add some more grapes? Sure, but you could also probably eat grapes too. You would just take something else like out or move it around or you would have more protein when you have the grapes or whatever different strategies we do. It's really small the amount of goos and powders and things like that that we're doing. We're going to eat 95% of their calories as whole real food. You've got a little bit of supplements on the end and things like that, but we're not going to spend too much time with low quality foods, even for those individuals. I want them eating real whole healthy foods. So that is a really small difference, I guess. So yeah, in some of those situations, for the most part, your diet and their diets would be very identical.

Rhonda Patrick: So fat often gets overshadowed by protein and carbohydrates. Where does fat come into the equation of meeting your fitness goals, whether you're an endurance athlete or strength training or not necessarily an athlete, just someone who's interested in being healthy and exercising and looking for the longevity aspects of diet and exercise?

Andy Galpin: Yeah, so I would say, I mean, you positioned it pretty well. Most people start with protein, lock that thing in, and then you'll play with carbohydrates and fat as a way to adjust the overall caloric intake. And because we know the role of carbohydrates in exercise performance, we will usually go to that second, and then fat gets the third consideration. Like, okay, fine, whatever calories we have left, we backfill with fat. And as long as your fat isn't too low and it's too low chronically, then you're not going to really run into too many issues with having insufficient amount of intake of fat, dietary fat. That said, this is something I've changed my tune on a lot, right? Like I come from the classic exercise physiology academic background, and all those people are carbohydrates first, carbohydrates second, third, fourth, and like fat was always shunned. And I don't think I believe that as much anymore. I also, we've experienced a lot. A lot of the people we worked with, they're fine on moderate to low carbohydrates, even high exercisers, non-athletes, but they train a ton. You're talking about guys and girls running 60 miles per week, right? Like real high energy expenditures in terms of performance, and they're at 100 grams of carbohydrate a day. They're not in ketosis at all. They're not even trying to be, but they just like are fine at 150 grams a day or 200 grams of carbohydrate a day, right? For 120 to 190 pound like individuals, kind of at that, just as some frame of reference for numbers there. In that case, their fat intakes are way higher and they're fine. We're not seeing any performance decrements, they're not having a hard time recovering, their sleep isn't going down, like sex hormones are fine. So I actually have seen enough evidence now anecdotally and empirically being like, I think actually you're fine there. I think you're okay. If you're giving yourself, if your endogenous recovery is sufficient, I think you're going to be just fine there. So what we do with carbohydrates and fat for that person you're describing is we let personal preference drive us a lot, right? We also will change it just so that you can have some dietary changes. Like fat tastes delicious. It's really hard, it's really bland when you don't get to have a lot of fat in your diet. So sometimes we'll bring carbohydrate down for a while and let them have more fat if we need to manage calories. We don't generally see that much for the average person. Like we don't see that many consequences performance wise. So I don't think most people are going to have this huge like, oh my God, I'm not recovering anymore. If you're doing a normal amount of exercise, I think you're going to be just fine.

Rhonda Patrick: Some people think if they're eating a high fat diet, low carb diet, and they're doing endurance type of exercise, they're more heavily biased towards endurance training, that they're going to be more fat adapted, they're going to be more metabolically flexible, and their mitochondrial adaptations are going to be superior.

Andy Galpin: I would not support that statement. I would disagree with that. This is a great one. So the term metabolic flexibility has been hijacked. And the way that it is described now colloquially is not what that phrase ever started to be, and it's not what that is intended to be. It's so crazy because metabolic flexibility has got turned into maximizing fat burning. It's supposed to be metabolic flexibility, which means you have the ability to run the whole gamut. I get it. If you pluck the average person off the street, they're probably less likely to be good at burning fat than they are carbohydrate. So on aggregate, we probably need to get more people better at burning fat. I'm with you on that one. But metabolic flexibility is not just maximize fat burning. Those are not the same thing. And that's how people will often describe that. If you go too hard on one side of the equation, you'll see a whole host of adaptations that compromise the ability to do the other things. That's not metabolic flexibility, that is still specialization. You're just specializing in the other side of the equation. If that's what you want to do, fine. We're all for it. But we generally like to see people truly flexible on both sides. So if you want to go higher fat in your performance because you feel better, you like it, great. If you can demonstrate no issues, we're all for it. But if we're doing it for a theoretical idea and you don't actually have information behind that, then we're not going to support those ideas. So you want to go higher fat? Great. We have had some people where we've tinkered around with some number of people. Actually, we've tinkered around with different things. We try a higher fat diet, and they actually do perform better. So we stay with that, right? Even independent of any metabolic flexibility data we've got on them, great. We're going to stay on that. And then we've had others that are the opposite. So these are these really long-duration endurance folks that are out there, and they just don't do well when carbohydrates get low. And so we have to have room for both of those realities. Some people will perform better on a higher fat diet for more fat-oxidizing, lower-intensity things, and some will just do a lot better on those. And to finish up the point, I'm talking about long-duration endurance events that are both fast and slow. So if you look at, to be ridiculous, like we were talking about Cam earlier, you look at Rob, producer, these guys are under 2.5-hour marathon times. Cam's higher, but Rob's at 2.5-hour. He's fast. He's going to be burning, I don't know, I don't have metabolic data on him, but 70% to 80% carbohydrate in the marathon. So that's a long-duration endurance event, but that is not a fat-burning event. That is a carbohydrate game, right? If you want to run a marathon fast, that is a carbohydrate game. If you want to run a really, really long one and you don't care about speed, you're still going to burn a boatload of carbohydrates. But now we can afford to go slower with more fat oxidation. And so when we say endurance, there's also another level of question. It's like, okay, fast endurance or just endurance for the long term?

Rhonda Patrick: Well, yeah, it does answer the question. It's basically like, no, you don't have to be eating a higher fat diet, isn't necessarily going to make you better at burning fat.

Andy Galpin: Oh no, definitely not. I certainly think that when it comes down to that metabolic flexibility exercise, again, when you're doing a lot of exercise, you actually are becoming more metabolically flexible through exercise, in my opinion, than anything else.

Andy Galpin: Actually, I think the one thing that's kind of interesting here that does get left, the way that we think about metabolic flexibility is more of an innate human skill rather than an exercise performance one, such that I think we all should have the ability to go for six hours and not have any food and still perform cognitively. You shouldn't be hangry and cranky because you missed lunch. Now you're not super resilient. Whether this is a metabolic flexibility issue or not, if that's happening consistently with you, I would say we have some room to grow with metabolic health likely, right? You should probably be able to go 24 hours and maintain cognitive function and maintain physical performance. If you've ever, you've done some fasting, like longer fasting stuff, right? You should be able to not eat any calories for 24 hours and still exercise, right? You will not deplete really of very much anything. If you're the person who is the like, I can't do anything, I skipped lunch or didn't get to breakfast, then I think we have some stuff to do. But this is more of like, you have probably are lacking some innate physiological skills that are going to help you in multiple ways. But past that, the metabolic flexibility thing is, again, not often packaged correctly in my opinion.

Rhonda Patrick: What do you think about, so I've had Marty Gabala on the podcast talking about high intensity interval training and how obviously when you're doing, a lot of people think when you're like doing HIIT that it's like this all, I'm only burning glucose, right? If I'm doing zone two, I'm only burning fat, I'm only oxidizing fat and using mitochondria and they don't realize there's actually a lot of gray going on. Like you're doing high intensity interval training types of exercise, you're, yeah, you're going above the lactate threshold, you're using glucose as fuel, but you're also still using your mitochondria, right?

Andy Galpin: There are many things to say about poor understanding of metabolism is how I'll say that. There is no way to fully metabolize carbohydrate without oxidation. You just can't, right? Like you can run through and we can do it, and it's probably not the most interesting thing, but you can't get very far anaerobically with even carbohydrate. You have to finish that story aerobically. Does that mean your fuel in the exercise itself is the same as the total net expenditure? No. So in the case of Marty's work and high intensity stuff, yeah, in the actual exercise bout itself, you're going to be well above anaerobic threshold. You're going to be well above an RER of 1.0, right? You're going to get really, really... In fact, we have seen many times 1.3s, 1.4s, right, for RERs or RQs. That's mathematically impossible. 1.0 means 100%. So what you mean is like the carbon dioxide expenditure is so exceeding aerobic or oxidative intake that your numbers get like astronomically high. So yes, but that said, anything you just burn there that's sitting either in lactate or in pyruvate or some other intermediate form there, it's going to be finished in the mitochondria with oxidation. You want to recover faster? And I'm talking about within the minutes to hours post-exercise as well as a couple of days. Now this is an aerobic capacity issue. That's how you handle these things. For our athletes that fight in five five-minute rounds, like in the UFC, or we do 12 rounds in boxing, whatever the case is, there is a huge aerobic component to that. Huge, despite the fact that they are going as hard as possible. They are pegged heart rate wise and other things. Getting them to recover, especially from session to session, the morning workout to the evening workout, the higher functioning aerobic capacity we have there—and I don't mean VO2 max per se there, I truly mean aerobic capacity—that is a huge component of their ability to recover and to not be completely trashed the next day. The ones that are really, really smashed anaerobically, like really high, they can't train as much. We have to back them off more. The volume has to be lower. We have to be really strategic. We run into injuries more frequently. We run into just physiologically running into the ground. Our recovery metrics get lower. The taper has to be longer. We have to just make adjustments with calories. They can't handle as much. The ones that are higher in aerobic fitness, they can handle things more. There's consequences of that too, but yeah, you can pick the highest intensity thing you could possibly do, and there's still... Anaerobic and aerobic is not two different things. It's the same gear. It's the top side and bottom side of the same gear. They're not different units. They're just the front side and the back side of that. They will always complement each other. They're not distinct things.

Rhonda Patrick: Right. No, it's true. I mean, but people like to kind of put things in bins. I think Lane explained this in a good way, how people just put things in bins, like it's this bin or this bin. It's rarely how physiology works.

Andy Galpin: It's rarely how physiology works. We have redundant systems on purpose.

Rhonda Patrick: I kind of wanted to ask you just because we were talking about the timing of... We talked about the anabolic window for carbohydrates, how there truly does seem to be an importance there with respect to at least if you're doing more endurance type of training and you want to be ready for the next day. But protein, you know, Stu Phillips has been on, Luke Van Loon, you're in agreement that really the anabolic window is more of a... It's more of the total daily protein intake, right?

Andy Galpin: Yeah, and honestly, that comes down, though, to practicality. It's just simply because I said earlier, it's just really hard to get 400 grams of protein in a day. So you just end up having to do protein like all of the... yeah. Right. Look at Mike Ormsby's work out of Florida State. He's done all that pre-bed carbohydrate stuff or protein ingestion stuff. So it's like 40 grams of protein 30 minutes before bed. Now, in all that stuff, he hasn't shown these huge massive benefits to it. He actually doesn't show any consequences either. So you don't compromise fat, you don't gain more fat, you don't reduce fat oxidation by having this big bolus of protein right before bed. And so the way he will package that is to say if you're struggling to hit your total protein numbers, this is just another window to get you there. If your protein numbers are fine, though, there's no added benefit, there's no huge win. And so that just is another example, I think, at this point, when it comes to the protein game, probably what Lane was saying, like if this is just maybe a way for you to smack in 15 more grams or 20 or 40, then great. But outside of that, there's no magic benefit.

Rhonda Patrick: Yeah, Luke Van Loon actually did a few studies. I don't know if he collaborated with the person just mentioned, but also on this pre, like pre-sleep protein loading where it's like they're giving people protein, a bolus of protein right before bed, and it does increase muscle protein synthesis while they're sleeping. And it, you know, again, I think the way he also framed it was you're, you're getting more of your total protein. You're getting more of that, you know, total protein for the day. But also it seems to make a difference for like elderly people who are just terrible at getting, making meeting that protein r

Luke Van Loon actually did a few studies. I don't know if he collaborated with the person just mentioned, but also on this pre-sleep protein loading where it's like they're giving people protein, a bowl of protein right before bed, and it does increase muscle protein synthesis while they're sleeping. And again, I think the way he also framed it was you're getting more of your total protein—you're getting more of that total protein for the day, but also it seems to make a difference for elderly people who are just terrible at meeting that protein requirement for whatever reason. I don't know. It's just hard to chew food or their appetite isn't—they don't have, their appetite hormones are kind of dysregulated, whatever the reason. So what I wanted to ask you about, because it was kind of interesting, I saw a study you were a co-author on with respect to protein, kind of on that sort of same token, people meeting—it's hard for some people to take in 1.6 grams per kilogram body weight or more, right? Tough. So they're taking protein powders, they're doing the protein powder. It's the easiest thing, right? What are your thoughts on whole foods versus powders? Now you published an interesting study on egg white powder versus the whole egg.

Andy Galpin: Yeah, yeah.

Rhonda Patrick: But I'd love to know your thoughts in general.

Andy Galpin: Yeah, that was actually a pretty cool study. Whole food is always the answer, right? That is always our default position. If we ever have to go to supplements or even supplemental food, like a protein powder or a powdered carbohydrate, that is our second choice, full stop right there. That particular paper and actually set of studies on that found basically the same thing. So whole egg versus egg white, and it turns out potentially we don't have mechanisms behind this, but potentially some of the stuff that's in the egg yolk itself was contributing to additional muscle growth, micronutrient-wise, vitamin D, right, of course, and any number of things that are in there. Absolutely, right? Whether those actually were the case—and again, we didn't have mechanism on them—it was just sort of like, "Why do you think this is happening, even when you match it for calories?" Seems to be the case nonetheless. So to back out your question, yeah, it's a whole food answer, right? If we can get there with whole food—I will say this: we have many of our professional athletes that take almost no supplements, and they definitely don't supplement protein powder. Some of them don't like it—it doesn't sit well with their GI. You don't have to have protein powder ever. I can't think of a compelling reason why, outside of practical, easier flavor, taste, whatever. So protein very specifically, whole food. Muscle growth, whole food. There are other use cases for other supplements and other strategies, but that is our answer, and I think that paper you're referring to showed the same thing.

Rhonda Patrick: Yeah, I was a little shocked, to be honest, because protein was equated, calories were equated, and they were training, and it's like the people eating the whole eggs had increases—I guess it was slight—in muscle mass.

Andy Galpin: Well, it was. Strength also, right?

Rhonda Patrick: Strength also, right. Yeah, but you would anticipate it to be slight. How much of a benefit would a couple of egg yolks a day plausibly give a healthy person? It shouldn't be much. Had those data come back and it was more than that, I would have been like, "I don't know about that." Yeah, well, it's a little interesting because you always think about, well, leucine is the major signal for protein synthesis, muscle protein synthesis, and you would think, "Well, if it's the leucine in the egg white powder, why is there a difference?" Right?

Andy Galpin: Well, again, this is what—like, it's actually funny because when the reviewers came back, it was like I knew it was going to happen. Everybody knew. And it was that, right? You're just like, "Okay, how?" We're like, "Well, I don't know. We don't have this." And so you just start making, as you mentioned, choline, and you start making, like, "Well, plausible this, plausibly that," and then plausibly that. Well, there's also some omega-3s in eggs, and you might think, well, the cell membranes—now maybe the transporters are getting more leucine in. Who knows? Totally. Who knows, right?

Rhonda Patrick: But I personally, you know, I don't like protein powders, to be honest, and it's a processed food. I mean, you look at protein powders, and it's never just protein—never. And so I have every reason to be motivated to eat my turkey burger, my homemade turkey burger, you know, versus the protein powder. But I get it. I get, like, I have these pre-made homemade turkey burgers—they're food prepped, and they're there, ready to just microwave. I'm not scared of microwaves, so easy for me to do. But there's a lot of people that it's like, "Ah, they're not going to cook something." If they don't meal prep, then it's the go-to, right? You're going, "I don't like protein bars." Same thing, where it's like, it's processed, it's all this stuff. So I kind of liked the little extra motivation to say, "Yeah, go for the whole foods. Go for the whole foods," you know.

Andy Galpin: I have had a love-hate relationship with those things as well—spent many decades smashing many scoops of protein powder a day, and then probably went a decade or more with almost no protein powder. Now I'm back on it a little bit more for other reasons, like they're getting better with some of those things. But if you're asking me what I'd rather do—have a candy bar or have, like, a piece of whole food—I'm always going to take the whole food for preference, just flavor preferences. Like, I like eating food more than I like supplements.

Rhonda Patrick: So we talked a lot about macronutrients. I think there was, you know—I didn't know if there was—going back to the fat, just before we move on to the micronutrients, is there really an optimal fat ratio or timing? I mean, or is it mostly come down to if they perform better, if that's what they want, or do you think that it's something that's just not as important as carbohydrates?

Andy Galpin: Well, I'll answer this two ways. I'll be short. I actually think it's an interesting question—I don't think people spend a lot of time studying it. I'm open to the possibility that there is way more important in different timing scenarios than we think, but that people just have not done that work. So that's an open-ended question that's never been there. The other way I'll say it is because of that, I guess, yeah—I just don't feel like at this point we have any compelling reason to think that it is a critical thing to pay attention to in terms of timing and stuff relative there. If you just think about plausibly what these different fueling sources are intending to do, it makes sense that fat is probably the thing you should be third concerned about. You have backup stores of it already, it can be mobilized when you ingest it, or you're using endogenous fat—it still happens at roughly the same rate, so on and so forth. So with all that, I think that's our answer, but I'm open. I'm open to other things.

Rhonda Patrick: What about—you mentioned earlier that you're mostly concerned if people aren't getting enough fat, and so I'd love for you to explain to people why that is, but also I'm interested in your thoughts about the quality of fat. Are some fats better than others? Do some fats hinder performance?

Andy Galpin: Yeah, this is actually a whole category of questions that are super interesting. We grew up in the same nutritional generation—right? Low-fat, low-fat, low-fat. And then we saw those consequences. Okay, if you are really low fat for a long time, there are a cataclysm of problems that can happen with that—especially if you're combining that on top of hypocalorism: endocrine disruptions, sleep disruptions, probably long-term health disruptions in many areas. It's going to be a huge issue. What does low mean? I don't think we have a great definitive number on that, but if it's less than 10% of your calories, again combined with hypocaloric for a long period of time, then you're probably running into all kinds of issues—from cell membrane, like, you don't have the basic building blocks to keep cells together, to the other ones: endocrine health, organ health, transporter health, storage health—it has so many roles in our body. So you want to stay away from those things. Now, past that, in terms of fat quality—boy, how inflamed... Your audience is probably a little bit better, but how mad do you want the internet to get about these following statements, right?

Rhonda Patrick: The truth is all that matters to me. Yeah, let's hear it.

Andy Galpin: All I know matters to you. You've been clear in your career of how you approach things, but there's just not a lot of compelling evidence that whole fat in itself can be disregarded as always healthy or always bad. So animal fat, vegetable fats, seed oils—we'll throw it out there—when managed under all proper situations, we're okay here. Like, we're really just okay. You're fine. We're going to handle these things. But you go exaggerating any one of those areas, you're going to run into problems, right? So if you're eating copious amounts of saturated fat and combining that with low physical activity, hypercalorism, you're going to have problems. Same thing with seed oils, right? You cook them, you process them, you do all those things—you're going to run into problems there too. So what does a quality fat mean? I always default back to the same thing: I don't want to eat anything that's processed. I don't care—animal, plant, you pick it. I'm trying to eat whole food versions of everything, and that is true for my carbohydrates, my proteins, and my fats. So we don't approach the fats that differently. So I don't deal with it that much because rarely are we going out of our way to give people processed foods—processed fats included. So when we're eating—for most of our people, they eat animal sources, right? So we're going to be getting fats from animals in a reasonable amount, and we're paying attention to those other factors—vegetables, protein, whole foods. So because of that, animal fat just doesn't come in huge quantities—we don't have the physical space—it comes in a normal amount, and we're okay. At the same time, we're not having to be so guarded against seed oils because we're not consuming most foods that come with seed oils—we don't have to worry about that.

Rhonda Patrick: Right, it's the company.

Andy Galpin: It's the company, right? These things are not critically—I know some people get so fired up about it.

Rhonda Patrick: What about olive oil, avocado oil, avocados, nuts? I mean, omega-3 fatty acids, fish—those are all...

Andy Galpin: If it's in a whole food, we have no issue with it, right? You have to be a little bit careful with exogenous oils, just because, as you're aware, caloric intake just gets really, really high there. But do we have our people eat nuts? Yeah. Avocados? Yes. Like, all of the above. Whole foods are almost always going to be on our list. You just be careful with additives—like, you put something into an oil in low quality, in the sunlight—fill in the blank there. Same thing with nuts, right? Those can come in low quality as well. So we always try to get those things in the appropriate standards, and then we don't have any issues past that. So I don't know how much we've successfully dodged or didn't dodge any landmines on that one, but man, I just don't have a lot of aptitude for—

Rhonda Patrick: I mean, we'd have to spend hours talking about it because it's so much nuance. That would be a whole other—

Andy Galpin: Thank you for saying that so I didn't have to say it. That's one kind way to put it, but my goodness, people.

Rhonda Patrick: Yeah, there's a lot of emotions involved in nutrition, for sure.

Andy Galpin: That's a great way to put it. There's a lot of emotions involved.

Rhonda Patrick: So micronutrients…

Andy Galpin: So micronutrients—vitamins, minerals, phytochemicals—if you're doing your job with nutrition, those things are mostly taken care of, right? If you're eating the variety of the foods, the type of foods that we've been talking about, the big basic stuff, you're in a really good spot. Now, do we need to go on top of those things and supplement particular vitamins, minerals, nutrients? Context dependent here. Magnesium is the one that jumps off, of course, as the one where if our food quality sources were—I don't want to say how they used to be or what we would like them to be—and we had adequate amounts of those in our food, then we would literally just not have to worry about supplements at all. But that's not always the case. So because of that, you can look and you'll see all kinds of numbers about things like magnesium deficiencies—whether that's clinically deficient, subclinical, or just suboptimal. I don't know, some papers 40% of people, some people 60%. Like, those numbers can get really, really high. When you look at athletes—because of caloric expenditure and because of sweat and because of how much tissue breakdown that's happening through many—then the needs are even higher with them. So I would say magnesium as a supplement comes in probably 90% of the people we work with. It's really, really, really common for us to add magnesium as a supplement. We try to add higher magnesium bioavailable foods more—that is our starting place—but we're probably going to add supplements on top of that in addition, because it's just hard to get there. You've got to be careful with this a little bit, though, because if you were to look at your magnesium levels in, like, a classic blood draw, that's a terrible place to look. The magnesium that comes on your blood work that you get is not indicative of all of what's actually happening in your body. The vast majority of it's going to be stored in bone anyways, and it's super transient. Now, there's good information you can get there, and there are other ways you can look at it—markers of it—but I always like to flag that because people get really freaked out. They go in for blood work for whatever reason, they see that, and they're like, "Oh, I'm super high, I don't need it." Like, no, no—that's not a good way to interpret your overall magnesium status. We can talk more about that, but in general, because of those things, we end up adding magnesium as one of our top-line micronutrients to pay attention to. So I'll go on for more, but I'll stop on magnesium if you want to talk more about it.

Rhonda Patrick: Yeah, for sure. I'm glad you mentioned the plasma levels magnesium, which is mostly what's being measured in a standard test, I guess you would get from, like, a routine physical or something like that. Yeah, you pull it out from your bones, and really it's kind of like this—your bones are this reservoir, and by the time someone reaches older age, like 50% of their magnesium has been taken out of their bones. I mean, it's incredible, and it plays a role in osteoporosis. A huge role, but people aren't really focused on that as much. Yeah, so about—if half the country isn't, as you mentioned—it depends on the paper that you're reading and what's being defined as magnesium insufficiency. Most of the time it's looking at what the RDA is—so for women it's about 320 milligrams per day, for men about 420 milligrams per day—and so people aren't meeting that requirement, so they're considered to be getting insufficient magnesium. And so you're talking about half the country basically, so you've got a one-in-two chance of whatever athlete that walks into your door, they might be not getting enough, right? So it's kind of—I would say that it's good insurance. But then, as you mentioned, these athletes are sweating magnesium, they're breaking down tissue, they're urinating more—I mean, there's lots of…like, it's coming out, it's coming out. And so they can require up to 10 to 20% more than the RDA, and so if they're not even meeting that RDA, it makes sense to supplement. Now, I've heard you talk about different magnesium supplements, like magnesium citrate being one that is often preferred for recovery.

Andy Galpin: Magnesium source is different. Back when we were kids, you had to be really on top of this because of ineffective forms of magnesium and because of GI distress. Most supplement companies have cleaned that up, so now you can look at bisglycinate—it's a really common one—that is fine. Citrate's fine. Obviously threonate's become more popular now. Any of those are generally okay, right? It's the old forms, the oxidates, the different ones like that that you really had to be careful of, but you're generally okay there. They've also in large part dosed these things so that GI distress is not huge anymore. So this is actually something we would pay a lot of attention to way back in the day, but for the most part, you're okay as long as your dosage is reasonable. If it is giving you problems, then you can go down a little bit, or you can try a different form. But we haven't seen huge differences between various forms—they're all basically getting to the same spot. So, like, most of our people coming in, the closest accuracy you can look at is…it's not uncommon for us to see people below 250 in terms of their intake. So like you said, 320, 400—that's not an athlete, that's the standard person. Athletes can be 20% more. So we actually have generally found our non-athlete, our normal people population is generally higher magnesium intake; our athletes tend to be lower. That's a little bit of—well, that's a lot of—selection bias: someone's coming in to work with me, they're probably pretty health conscious; the athletes are not always health conscious. So it's a little selection bias. Yeah, but really common—so much so that, to be candid, I barely look at it anymore, because I'm like, I just know, I assume you…

We will see pretty pronounced improvements in a bunch of sleep metrics though. That seems to be real. And that's all very objective. Like our sleep technology is incredibly advanced that we use. It's not just like a consumer wearable. And so we have a ton of metrics we can look at there. And that one seems to be a really clear jumping off point. And it doesn't seem to matter which form we use.

Rhonda Patrick: That was my next question. Yeah.

Andy Galpin: Not surprised. No, I mean, there's been actually probably two or three papers in the last six months on three and eight specifically. We're finally starting to get human trials, need more work. But we haven't noticed a big difference between forms. Most people aren't three and eight right now, but not a big deal for us.

Rhonda Patrick: What about, so omega-3s, and I do want to talk about—we're going to get into recovery and supplements for performance as well—but omega-3s is another one. I mean, I personally, as you probably know, think that most people are not getting enough omega-3. In fact, if you look at data on the omega-3 index, people are mostly not, they're in the low range. And there's a lot of longevity reasons—cardiovascular health, inflammation—why getting up to a higher omega-3 index would be ideal. And most people—there's been studies showing that taking around 1.5 to two grams a day will get you there from a 4% omega-3 index, which is low, to an 8% omega-3 index, which is high.

Andy Galpin: The omega-3 and heart palpitations is great. If you are a cardiologist, you can treat that however you'd like. If you're concerned about it, work with your cardiologist, do whatever you want. But outside of that, there is so much other information, so much benefit, so many rational reasons for omega-3s that we use it very consistently. We always start food first, blah, blah, blah, all the things. But because of that, a moderate to low dose of omega-3, pretty safe place to go.

Rhonda Patrick: Yeah, on the AFib thing, it seems to be at a four-gram, super-high-dose range, four grams ethyl ester form. And also, the recent paper that came out, it was a correlation paper. It wasn't a randomized control trial. Bill Harris is publishing a response to that. It was, like, terrible statistics and all this stuff done. Did you see the absolute effect, by the way?

Andy Galpin: Yeah, it was extremely low. Ridiculous. So I think it was just creating a lot of anxiety. Of course, there's people that maybe have a family history or are prone, maybe shouldn't be taking five grams of ethyl ester, high Vascepa or whatever a day. Man, I got torched for that recently.

Rhonda Patrick: Really?

Andy Galpin: Yeah, I talked about it somewhere. People flew off the handle. I'm like, "My God. You have to pay attention past the top line. You do. Look at the absolute effect." Again, it's like one of those things where you're going to have to spend a little bit of time talking about all the nuance to really convey everything. You can't just do a little sound bite. People are going to have their emotional response, and that's that. There's also just—look, humans are weird. You can't pick an exercise, a supplement, a nutrition thing that we've ever done where somebody of the 7 billion of us won't throw their hand up and go, "Oh, I did that, and I had this crazy negative response."

Rhonda Patrick: Right.

Andy Galpin: Yes. Totally happens. And I believe you. I trust you. I can't explain it. Physiology is wild.

Rhonda Patrick: There's nuance here. People respond differently. Not to mention that maybe it was something else. I mean, like, you never really know. But have you—so I had a young professor on the podcast, Chris McGlory, and he's been doing some pretty pioneering and interesting work. He trained with a couple of the big guys—Stu Phillips is one he trained with—but he does work on high-dose omega-3 and disuse atrophy. And he's done a couple of randomized controlled trials showing it has to be preloading, because it's completely independent of the inflammatory effects, anti-inflammatory effects of omega-3, right, where it seems to be you have to get these people on omega-3 for at least a month, right? They're doing like four or five weeks before the trial starts, so they have to be loaded up—that's how long it takes to accumulate in cell membranes—and it's accumulating in their cell membranes, in their muscle, and people then have a disuse event. So he'll get a cast or whatever on them, and it cuts disuse atrophy like in half. And he's like, you know, trying to figure out what's going on, but it appears to be sensitizing muscle to amino acids. So it's almost like what exercise is doing.

Andy Galpin: Yeah, yeah.

Rhonda Patrick: Which is, of course, when you're having a disuse event, you're not exercising. But anyways, it's something interesting I kind of wanted to throw out there and get on your radar, because it's kind of in your world.

Andy Galpin: Yeah, look, you'll see a cornucopia of things like this. When you take people—I would assume, I don't know his population database in that trial, but I would assume it's fairly inactive, unhealthy people.

Rhonda Patrick: Women, young women.

Andy Galpin: Okay. The only reason I'm saying that is you seem to see these type of crazy things happen when you go from, like, somewhat suboptimal to poor health, and you just get them back to baseline. Wild stuff just starts happening like this. I have no idea. We could probably get a whiteboard out and start tossing up mechanisms, figure out, like, what's plausibly happening there. But you could infer just, okay, a healthier cell membrane probably then can do a bunch of things that it was trying to do but wasn't healthy enough to do, however we want to determine healthy, and now it can. Could it be a reactionary response? Could it be all these things? Yeah, awesome. That is quite different than going from already pretty healthy there. So I would imagine that case, if you take people who are already pretty healthy and do the same thing, you wouldn't see as much of a response. But that goes to the point of saying, okay, now given the fact we know most people are not already pretty healthy.

Rhonda Patrick: These were healthy women. I think that generally speaking, healthy—so we're looking at the effects of omega-3. They didn't have high levels of omega-3, right? So the idea is you take someone that's already eating fish, they're supplementing with omega-3, they're exercising, whatever, and so you put them in a disuse event where they're not moving a limb for four weeks or whatever, and healthy or not, they're going to lose muscle mass, right?

Andy Galpin: Yeah, yeah.

Rhonda Patrick: So it's kind of interesting that—you take something like omega-3s, which are known to affect transporters, receptors, anything embedded in the cell membrane, and makes it better. It makes it functional. So when you have a deficiency of it, they're not as optimal. So it's kind of interesting because—

Andy Galpin: Super interesting.

Rhonda Patrick: For me, it's not just important for, like, elderly people and perhaps a surgery or an event—a disuse event you can plan for—but I think just injury, like in general, having these omega-3s in our cell membranes built up to that level already would be important. But also, what about recovery? Have you looked at omega-3s in recovery at all?

Andy Galpin: Not in my lab ever. Yeah, I don't think I've spent a ton of time outside of the obnoxious, again, going from deficient, super low, just back to a standard number, going from good to high. No, I don't think I have anything super interesting to say on that stuff.

Rhonda Patrick: Well, to be determined some other time. I do want to get into some of these performance enhancers, and this is kind of—you know, it's an area that I'm interested in myself. As we were chatting earlier off camera, I had recently had Darren Cando on the podcast, and he's done a lot of research in the creatine world. And so I'm kind of curious. I take creatine now, but I wanted to ask you about, you know, the top sort of performance-enhancing supplements, and then we can kind of get into some of those, just kind of what your thoughts—I'm sure creatine's at the top of the list.

Andy Galpin: Yeah, of course, right? Like, how is that not going to be on the top of everyone's one? The way that we would think about supplements in general is, number one, remove, reduce, try to eliminate any physiological insufficiency, whether that is coming because of caloric restriction. So we have dealt with a lot of people, whether this is, again, as our athletes or non-athletes, where caloric restriction is a thing. And I'm saying that because that's why supplements tend to be helpful. I would prefer you to get all your stuff from food, but when food is limited for a bunch of different reasons, now we can use supplements to backfill vitamins, nutrients, minerals, and a bunch of other stuff. That is our top-line performance enhancement. When your physiology is in a healthier spot, it will perform better. So we can get into beta-alanine and other things for sure, but that's really important for me to state because that is where we have actually seen by far the most enhancements in performance and recovery and sleep and cognitive function, you name it. It's by just making sure—we call them performance anchors—you don't have any anchor behind you. Nothing's just dragging your physiology down. We get that thing solved, get it up back to normal, and then for the most part, I want to step away. I want to let your physiology just run how it wants to run. But if we have big holes, we plug them first. Whether you want to pick your metric as, again, recovery, muscle growth, testosterone levels—pick your thing that's going to get your brain most excited—that's where we see the most impact, like by a landslide. If your house is cleaned up there, now we can get into creatine, beta-alanines, you can get into fatigue blockers, you can get into stimulants, you can do a whole bunch of things like that, adaptogens. There's a whole host of things we could cover there. But that part of the equation is where most all of you will most likely see your biggest benefits.

Rhonda Patrick: Right. So pretty much the things we've been talking about. You want to make sure you're optimizing your diet, making sure you're getting your micronutrients, your magnesium, vitamin D, I'm sure.

Andy Galpin: Yeah, we do this actually quite differently. We spend a lot of time on a bunch of biomarkers. So we take a ton of blood, a ton of urine, stool, and saliva, and we get really precise with vitamin, mineral, nutrient recommendations. It's hard to get into that on a podcast without exact examples, but that's where we get. So yeah, we can start off with general recommendations, but being precise to physiology, we're able to paint pretty good molecular portraits of people and figure out what's happening with them over time and then get really specific.

Rhonda Patrick: Some people are really into measuring and trying to quantify their deficiencies and their sufficiencies and see what's best. But not everyone—not everyone's going to do that, right?

Andy Galpin: Yeah.

Rhonda Patrick: So some people, you kind of put them in that bucket of, okay, 50% of the country's not getting enough magnesium. Most people are not getting omega-3s. And the vitamin D, again, more than half the country's not getting enough because we're spending all our time indoors. And so you kind of go for the biggest ones that you're like, probably going to help, right?

Andy Galpin: Yep.

Rhonda Patrick: It's always better to measure things though, right? Especially with things like vitamin D, where you can measure it—it's a simple test—and most doctors will do it.

Andy Galpin: Yep. And vitamin D is a good example. It's also one where I feel pretty good with you just taking vitamin D without a test. I ain't tripping if you're just like, "Hey, I want to take vitamin D." Like, all right, I'm probably cool. What's the worst that's going to happen? Not much. Very limited downside, strong likelihood you're low, even if you're not low, very little harm here. So most of the things we've talked about, you don't need any test at all to go do. Some things, I'm going to say, "Hey, we want to see actual markers on this before we start tinkering with that." We said minerals in particular—be really careful with. You have big downsides with them. But yes, most people, the big stuff, we're going to put you in a better spot, and that's what to pay attention to.

Rhonda Patrick: So the minerals that are sort of not as risky would be the magnesium. Now, iron, you said—iron is something that probably is more focused on with females that are menstruating, right?

Andy Galpin: Yep. Premenopausal females.

Rhonda Patrick: A lot of them can become low iron.

Andy Galpin: And reds—red's a really common thing to pay attention to. So this is a concern you have with relative energy deficiency, right? So if you're not only combining being female as well as a lot of caloric expenditure and calories are moderate to low, then we have all kinds of problems we have to pay attention to there. So there's just a whole bunch of other factors that go into that. Iron gets really complicated really fast, so maybe we can come back to that one on a different day.

Rhonda Patrick: But don't you also, like, as an athlete, you're losing your tear-down—like, red blood cells are being torn down—and so you're probably losing even more iron.

Andy Galpin: Okay, so there is a thing that we will talk about for many decades now called heel strike hemolysis. This is exactly what it sounds like. If you run a lot and your feet smash the ground, when your blood is going past the bottom of your foot—just normal blood moving through your body—and that blood is between your foot and the ground, and then you smash it, you will smash your red blood cells. We see this in our combat athletes, right? So you have physical things hitting your body; you will physically smash those red blood cells, you will smash that iron. And so, yeah, it's not just menstruation, it's not just breaking down of tissue; you will actually physically smash your own red blood cells. So it is a huge concern for not just females, but young, old—it's a whole thing. Iron is big. It's also insanely related to sleep quality. So you will see numbers go all over the board when you are having splenic contractions at night because you're having mild sleep apnea or other disturbances. So the numbers that you're paying attention to there—they really throw people for a loop when they're blood work. So you got to be really careful in paying attention to that. And as I said, that's not an innocuous supplement. You can't just smash it and be like, "I'll just take some more." Not a good idea at all.

Rhonda Patrick: So you definitely want to measure your iron, your ferritin. Like what are the main things?

Andy Galpin: A bunch—yeah, I would say that there's probably at least seven markers that we would pay attention to before we're really truly understanding what's happening with your overall iron status. Everything from hematocrit to hemoglobin, ferritin, of course, but then you have even red blood cell magnesium concentrations, maybe probably closer to 10, actually, I would pay attention to. Mean corpuscular volume—there's a bunch of different things that we would look at. So yeah, but we'll come back to that one just because I'm stopping myself from going—this is going to be a 40-minute part right now.

Rhonda Patrick: Okay.

Andy Galpin: Because the reason why I don't want to do it right now is you can't get your toes deep in this without just making more confusion than not.

Rhonda Patrick: Yeah. Got it. It's one—okay, well, you mentioned stimulants, cognitive enhancers, and that's something I'm interested in. Starting with, of course, caffeine. And that's probably one of the most widely used stimulants globally. And I'm sort of—I've come across a few studies where caffeine, if used before exercise, seems to enhance fat burning, like pretty significant. And now this is not someone that's already an athlete and doing long amounts of endurance exercise, it's not going to make a difference, but someone like myself—I'm running a 30-minute, doing a 30-minute run, or I'm doing a 20-minute HIIT—I don't know. This might make a little bit more of a meaningful difference to me.

Andy Galpin: I wouldn't—I'd be skeptical on that one. Caffeine works, no question about it. It works as an ergogenic benefit. You will perform oftentimes better.

Rhonda Patrick: Boom, that's it.

Andy Galpin: So there you go, right? Like, if you burn more calories, train harder, went faster—yeah. Now, will it have a lipolytic effect? Yeah, you take it right now, you will see free fatty acids go up in your blood. That will happen. You don't do anything with it; they will be restored and placed right back in their position. So if you look at the research on even fat burners, you're not going to really significantly aid in fat loss, right? Stimulants—caffeine, combinations of them—they are an acute effect. If they are used then to train better, more frequently, more motivation, work harder—great. Sometimes they have an appetite suppressant effect as well, but that's how they're getting to any substantive fat loss, rather than the actual mechanism itself.

Rhonda Patrick: Absolutely. Yeah. So it's essentially just you're working harder, kind of like with creatine, right? You're more volume, training, performing better. And so, whatever the reason—motivation. What about the dose of the caffeine, does that…?

Andy Galpin: Yeah, I mean, typical doses, you're going to look at something like—most is 150 to 400 milligrams-ish on those things. Way back in the day, people were tinkering with 10 milligrams per kilogram, so you're getting really high dosages, and you're in these trials, and you're just sitting there, and you're like—your head is going to explode. These numbers are outrageous. Four to five is more of a standard one now, which is going to equate to, like, 200, 300, or 400 total milligrams, depending on your body size. You start crossing past, like, 500 milligrams of caffeine, and you might have an existential event. You're going to be like, "What is happening?" And I just remember sitting there with other students and stuff just being like, "I just want this to be over with." You just do not feel good at those high dosages at all.

Andy Galpin: ts, caffeine, combinations of them. They are an acute effect. If they are used then to train better, more frequently, more motivation, work harder. Great. Sometimes they have an appetite suppressing effect as well. But that's how they're getting to any substantive fat loss rather than the actual mechanism itself. Absolutely. Yeah. So it's essentially just you're working harder, kind of like with creatine, right? You're more volume training, performing better. And so whatever the reason, motivation. What about the dose of the caffeine? Does that? Yeah. I mean, typical doses you're going to look at something like most is 150 to 400 milligrams ish on those things. We, way back in the day, people were tinkering with like 10 grams per kilogram, milligrams per kilogram. So you're getting really high dosages and you're like, you're in these trials and you're just sitting there and you're like, your head is going to explode. Like these numbers are outrageous. Four to five is like more of a standard one now, which is going to equate to that, you know, like two, 300, 400 total milligrams, depending on your body size. You start crossing past like 500 milligrams of caffeine and like you might have an existential event. Like you're going to be like, what is happening? And I just remember sitting there with other students and stuff, just being like, I just want this to be over with. You just do not feel good at those high dosages at all. So the downsides would be at a higher dose, depending on the person. Some people are pretty sensitive, but how can someone know if it's actually affecting their performance? Okay. So that's actually, there's a lot of conflicting research as well on adaptation. So there used to be this idea that you want to desensitize yourself to caffeine. So even if you're a normal habitual caffeine user, let's just say an average dose of caffeine in a, say a coffee or an espresso is 200 milligrams, right? Like whatever tea is less and you get the idea. So if you say you do two of those a day and you're like a three to 400 milligram per day user, you would come off of it entirely for a day or five days or something like that. And then you would reintroduce it and you would have this like super response. You will feel that. But the question was, is that actually then doing anything for performance? People would do this in like the powerlifting, weightlifting worlds and even in the endurance world for a long time. But there's more recent data that suggests it probably doesn't matter. There doesn't seem to be a correlation. Well, it doesn't seem to be a hundred percent crossover between your perception, your personal stimulation of it and the performance benefits. Those seem to be disentangled quite a bit. So even if you're normally at 400 milligrams a day and then you take your normal 400 milligram dose and you don't feel anything different, you might still have those performance benefits. You don't have to feel like you're super stimulated to get that thing. So those data have changed over the years, right? It's gone back and forth. It has to be novel, and now it looks like it doesn't really matter that much. So that game of like, do you run a resensitize or desensitize yourself? I leave it up to people, whatever you want to do. Generally, we don't worry about it, but it seems to be the performance benefit. So how would you know if your performance is getting better? We used to have to have some objective marker of performance. Like, are you lifting? Are you running? Like, what are you doing? Are you either going more? We'll back up. The two ways that we would typically do this in the lab is like a time trial, right? Or maximum performance. Like, so you can play the game. So you can say, we're going to lock this in at 30 minutes and say, how much work can you get done in 30 minutes? Oh, you got more work done this time than you did without the caffeine. Or the opposite. We're going to run a 5k and does your time get better? Like, those are the kind of the two ways to pay attention to it.

Rhonda Patrick: So I've heard you talk a little bit about – you and Andrew Huberman talk about rhodiola rosea. Yeah. And I've been sort of interested in this as a fatigue reducer, cognitive enhancer. I'm kind of interested. How does it work? How does it compare to caffeine, dose, all those things?

Andy Galpin: Yeah, rhodiola has been around for a long time. I've probably been using it, I don't know, at least a decade or more. It was always hard to get, and you were scared of where you were going to get it from kind of thing. You don't really know. Now we have enough data on it. There's quality providers, NSF-certified places and such. More research is coming out, muscle endurance in terms of like how many repetitions can you do of 30 reps versus 35 reps, like that kind of muscular endurance. And then we're seeing benefits otherwise. Andrew talks a lot about like he feels cognitive stuff from it. I don't really personally there, but to each their own. How is it working? Nobody knows. We don't really have – outside of like stuff in yeast and I think there's some fruit fly data, there's not a lot of mechanism here. I could guess. I could spout out – Is it an adaptogen? What is it? Is it a polyphenol? Well, both, right? So you have both of those effects. But the only little bit of mechanism data is maybe cortisol, right? Maybe something HPA access, maybe dopamine, maybe serotonin, like something's happening here. What you will generally see is if you look at markers like heart rate variability, what will often happen with rhodiola is the same dose of high-intensity exercise. When you use rhodiola, will not drive HRV as much. That's why we say it's like an adaptogen. That's why it mitigates the stress response. I have not seen any evidence that rhodiola would do something like improve baseline resting HRV over time. So it's not like a recovery agent, but it seems to make harder, higher-intensity exposure things not as damaging without compromising performance.

Rhonda Patrick: Right. Okay, so it's not compromising adaptations.

Andy Galpin: Correct. In fact, some data have indicated that. But most of the research suggests actual performance enhancements from it. We're just now with the cortisol and stuff, we're speculating. Because at some point, if you actually block cortisol response, then you actually inhibit stimuli, which you don't want. So our hands are up in the air. I haven't seen anybody really do a lot of human trials in figuring out definitive mechanisms. It's hard to get funding for these sort of things.

Rhonda Patrick: It is hard. Yeah.

Andy Galpin: But yeah.

Rhonda Patrick: What dose do you need to get the performance enhancement? Is it dependent on your body weight?

Andy Galpin: Always, right? But most products are going to be something like I think 150 or so is a reasonable starting point. I haven't really seen – like we've tinkered with really high ones. Some papers I think have done like 800 milligrams, like way up there. All at once? Yeah, yeah. I'm not going to lie to you and say we haven't tried that too.

Rhonda Patrick: Does it have a caffeine effect or is it like totally different?

Andy Galpin: No, no, no. So you don't feel like wired? Yeah, no. Great question. It's not a stimulant like that. We actually haven't seen any changes in sleep or anything like that. I would always take it in the morning personally if I'm going to use it at all, and we generally recommend the morning just in case. But no, not a stimulant in that sake at all. It's generally – again, the way to think about it is you take – if I were to put you in a placebo-controlled right now and gave it to you, you wouldn't know. I don't think you'd feel like anything. If I gave you beta alanine or if I gave you caffeine, you'd be like, whoa, like you know there. But we could blind you to rhodiola almost surely, and you wouldn't know it.

Rhonda Patrick: And what about in terms of like – you say taking it in the morning just to be safe, but like if you're wanting a performance enhancement –

Andy Galpin: You can take it at night, no problem. So it's like something that's in your system for a certain amount of time. It doesn't have to be like right before you work out. Yeah, we will use it chronically. Yeah, but again, we're speculating here because we don't know where we have mechanism. We understand at least roughly how a beta alanine or sodium bicarbonate are working or caffeine. I don't actually know. So I shouldn't back up. I don't know the answer to your question. We are not super worried about it that you have it right before your workout, but I guess it's plausible that we should, but we're not.

Rhonda Patrick: Well, 150 milligrams, I guess I'm going to try that out and see. I kind of want a little performance enhancement, especially in my strength training, my CrossFit stuff.

Andy Galpin: Yeah, I think that is a pretty good place where you would likely to see some benefit there. That would be a good place to try.

Rhonda Patrick: Okay. You mentioned the beta alanine. I want to get to that in a minute, but before, because we're kind of talking about performance enhancement, there's this whole category of these blood flow enhancers. And there's like the beetroot juice, beetroot extract, and then there's the citrulline, arginine. So I'd heard of the beetroot juice and these nitric oxide boosters, but the citrulline and arginine are something that I haven't really – I mean, arginine I know about for blood pressure, but not for this performance enhancement. So I'm wondering, endurance type of exercise or high rep type of exercise, I mean, is this something that actually can make a difference in someone that's already well-trained? Is it like not well-trained people? How much? Yeah. Talk about what it's doing.

Andy Galpin: Sure. There's actually a lot of research, right? Andy Jones has done so much stuff here. He's done a ton of work on it, and there's a lot. Like you're talking about a solid decade or more in lots of populations, lots of different stuff. So it is really well-studied. It's funny you bring it up because it gets no love. Like people don't talk about it that much despite – it's not a small amount of research here. If you want to especially stack up like rhodiola to beetroot: you have a mountain to go on with beetroot juice and you have a pebble on rhodiola. We like it. We use it a lot. I've used a ton of different forms over the years. It's great because it is not a stimulant. So you can take it in the evenings and it doesn't compromise sleep at all. We will all use it a lot for our individuals who are either exercising at night or training multiple times per day, and their stimulants come in the morning, but they still have high fatigue and so they want to use it in the evening. So that is our common use case. You see it a lot in the endurance world, particularly the steady-state endurance world, so cycling, swimming, running, things like that. You're talking about nitric oxide. This is a vasodilator. You're going to open up blood flow. You will feel it. If I were to put you in that blind test right now and gave you any of those forms you mentioned, you will be like, whoa, something just happened. There's no blinding to those studies. But it sounds like if it's increasing blood flow, it should make you cognitively more sharp as well. It will. I don't like it. Now, we're talking beetroot juice or we're talking citrulline and arginine? You're going to have the same answer for basically all the above. There will be noticeable effects. There are differences between all three of those. If you were to take literally beetroot juice and concentrate it into like a three-ounce shot, you could see the same stuff here. Most of the time with like citrulline and arginine, though, you're getting really high concentrations. I don't know typical dosage of those off the top of my head, to be honest. But what you're going to normally see there is a very pronounced stimulant effect. It's not going to be caffeine, but you're going to be like whoop, especially citrulline. You're going to see that right now. You will see if you go to the gym and you take any of those forms, particularly like the arginines have fallen out of favor. They're not as popular anymore for a host of reasons. But even the beetroot stuff, you will see a pump, a physical pump. I was reading about that. Yeah, yeah, yeah. That's not fake at all.

Rhonda Patrick: What's better, beetroot juice or beetroot extract? I mean, I typically go for the low sugar, which would be the extract. But does it matter?

Andy Galpin: We use extract more. You could make a compelling argument, though, that juice is better. You could do that. So it kind of depends on multiple parts of that equation. We use the powder, though, for a bunch of different reasons. A lot of them are practical. A lot of them are travel related, right? You don't want to take a whole bunch of juice with you in your airplane and you're flying all around to different places and you're just like, all right, I can take the powder supplement. It lasts longer, shelf stable. If we're talking about like antioxidant polyphenol properties, well, we know we're losing them in the powder. Like we're probably losing some of that relative to the juice. Okay. But then we're going to backfill that with whole foods and other things there. So lots of research on both of those. I would say a lot of people would

Rhonda Patrick: We will sometimes use it hours before exercise when we have high fatigue, high motivation issues. So you're like, you start having these associations like, let's say for example, we have somebody training at like four o'clock in the afternoon. And at two o'clock, this is when we start having problems with like, am I going to train today? Am I not or whatever? All right, let's give them a little hit right there. And we don't want to go to caffeine. We don't want to go to other stimulants like that. So we'll simply use it as like an afternoon pick me up, if you will, for even on a non-exercising day, if we're trying, especially if we're trying to get caffeine out of somebody's equation or lower it in the afternoon. So we use it then as just simply like, okay, motivation's back up. I'm feeling good again. And I'm ready to go. You'll feel it. Can you use it with caffeine? In other words, like, okay. So what are the downsides? I mean, it affects blood pressure, presumably, right? I think I remember reading studies about that years ago, at least beetroot.

Andy Galpin: This is nitric oxide, right? So this is your primary health concern is going to be anything related to blood pressure, right? So you handle those equations. Our downside, GI. Like GI distress is going to 100% be there. With beetroot or with citrulline? All of the above, particularly the beetroot. So the juice there. If you eat beets and you forget, and then you go to the bathroom, like, so that's the part of you're like, oh, you can freak, people can freak out and they forget that they took it. They don't know why. So you can have things like that. But as long as you're not GI issues, very minimal concerns outside of if you have, again, medical conditions that you got to pay attention. Do you have a preference to citrulline versus beetroot? Beetroot. Why? Yeah, generally we're going to be there. The issues, issues is a strong word. The slight things we've had to consider with citrulline is power. Like it's just too powerful for some people. They're just way like, whoa, like this is too much for me. I don't like it. I don't feel it. So you can titrate those dosages down. The other, again, issues is the wrong word. Issue is too strong. But the other like little bit of like, we've had is, why can't I just get this out of something closer to whole food? Okay, so if that is your preference, then we can go back up a little bit to beet or beetroot juice. But that's not a strong argument. Yeah, what about just baking some beets? Would you get a similar effect or would it not be concentrated enough? Probably like 15 years ago, I had a friend who you know, actually you met before, who did this. And he would blend beets, like in a blender. In a smoothie or something? Like you could call it a smoothie, but he would like juice it and blend it and he would do a combination. It was probably like eight to 10 whole beets he would consume pre-workout. And he did it about three times, I think. And two of the three times, he just threw up everywhere. And then he's like red. You can. It's a dosage issue though. Will you get a small benefit? I can't, like I've never personally felt like a blood flow benefit from eating a bunch of beets. Personally, some people say that they do, but you wouldn't get the dosage. That's why they're juiced, that's why they're concentrated. Now you said arginine's fallen out of favor. Why is that? Okay, so like you're probably pretty aware of nitric oxide metabolism. You can't just consume nitric oxide. Nitrite, nitrate, like immediately, like you're toast, right? So then the argument is, can we go back up the chain? Like can we go up to arginine? Can we go back up the thing? And so the first stop on that train was arginine. And then the issue you're gonna fall out there, which is almost always the case with supplementation, was bioavailability. Like how can we just get enough of it? And that one just seemed to fail. Well, it just seemed to get better once we started going there. And then there's other concerns, cold sores and things like that that started popping up that people were like not super stoked about. And so citrulline seems to be the better approach right now. That's the short version.

Rhonda Patrick: Okay, got it. Yeah, the arginine is used for viral replication. And yet that was a kind of an interesting, I mean, I've never tried, but I was reading a little bit about the cold sore thing, and I was like, I guess if someone has herpes, cold sores or whatever, that might flare them up or something. But I'm gonna try the beetroot. It's totally worth it. I experimented with it like 10 years ago for blood pressure, and I was giving it to my mom. But I just, I couldn't, at the time I was more low carb and I couldn't find a quality source. I'm sure now it's probably, there's like great sources of it, but yeah. So now I think I'm gonna go back, circle back, and try it out again.

Andy Galpin (unlabeled at start): It's been around for a really long time. Really simple strategy with this one. So enzymes work in a certain pH range, right? If you come too acidic inside of a muscle, we have a hard time running any metabolic process. Aerobic, anaerobic, strength, it doesn't really matter, right? Contracting muscle power. We start running into acidic environment, we start running into problems. So enter then a whole cascade of supplements designed to buffer fatigue, which is a way to say, like, let's keep you within that acidic range. Now you can do this by starting off more alkaline, or you can just do this by putting intermediaries in there that say, like, we're just gonna keep you within that certain range so you don't get too high. Beta alanine was a great stop on that because we're looking at intracellular carnosine. That's what we're trying to do, right? So he's like saying, hey, this is our limiting factor, beta alanine being the amino acid limiting factor. So if we can give you more of that, you can build up more carnosine, then we can buffer more effectively. And it works. There's a good amount of research on it. It worked for the things that you would anticipate it working for. Doesn't do much for maximal strength, doesn't do much for speed or power, doesn't do a lot for long duration endurance. Though again, you can see some positive benefits there. Where it mostly works are things of really high intensity, and by that I mean cardiovascular intensity. So high intensity strength training, again, I just said not super relevant because you're doing two reps. Acidic is not the problem there. So beta alanine is something that you would take chronically. You will feel an acute effect, certainly at somewhat of a higher dose, but you need three to five weeks for this to build up intracellularly before it makes a difference. And so much like caffeine or creatine rather, unlike caffeine, this takes a while for you to dose it, so you can do a bunch of things to mitigate that, but you will see a pretty classic. CrossFit would be a great example. Like, you couldn't basically couldn't engineer a supplement better for acute or for CrossFit performance outside of beta alanine. And as I mentioned, it's been around a really long time. It's just an amino acid. It's not a stimulant. It won't affect energy. You can take it right now. And again, you wouldn't notice; you wouldn't be like, oh, I'm fired up and ready to go. You wouldn't feel anything different, but you would just feel the burn is not as bad as your training.

Rhonda Patrick: What. What would be the optimal dose?

Andy Galpin: Man, I'm blanking on doses right now, to be honest with you.

Rhonda Patrick: So we can look that up. But I. I did read that there's some kind of tingling effect.

Andy Galpin: Oh, yeah. Back in the day, we would say, like, this is an iocine dump, but that doesn't seem to be the case. There's actually a couple of papers that came out. It seems to be something to do with sensory input. So there are some sort of sensory receptors that are being clicked on and tingled, and it kind of feels like a fire. It feels like you're itching. Feels like you rolled around in grass a bunch, right? Don't tell anybody this. We would give people beta alanine a bunch, like our friends, as a joke when they're, like, not paying attention. So you, like, put some, like we were younger, and so you're, like, sitting there doing work, whatever, all of a sudden you just, like, start itching everywhere.

Rhonda Patrick: You're like, what the...

Andy Galpin: We would do this a bunch. I did this to my wife one time, actually, and she was like, what is going on. She's like, something's—yeah, but that's.

Rhonda Patrick: Like a higher dose, right?

Andy Galpin: Not even, like, a moderate dose. You'll feel that.

Rhonda Patrick: Really?

Andy Galpin: Yeah, yeah.

Rhonda Patrick: Can you just. Can you.

Andy Galpin: It'll desensitize super fast. You can also just back dosage down. You just go down a tiny bit, and you'll find that level of like, okay, I feel fine. And as soon as you start training, it typically goes away. So 30 to 45 minutes before or so you take it, you'll start feeling those itchy, crawly feels a little bit. Generally, as soon as you start training, it goes away. If that's still bothering you, just lower the dosage. What we'll do a lot of the times—because it's not an acute stimulant—is we'll just split the dosage up throughout the day: half in the morning, half at night; a couple grams in the morning, couple grams at night, like that. That is a general place that we'll go. So like if the four grams is killing you or you don't like it, or three is better, then again, split them up throughout the day, and it won't have any effect. You will develop a little bit of a tolerance to that, though. So this is one of the cases where we actually want to build that dose over time. So when we get within, like, eight weeks of competition, we will start strategically increasing that dosage to get that as high as we possibly can. Where other things, we don't have to worry about dosage going up.

Rhonda Patrick: What should you—is it like a cycling kind of thing where you cycle it?

Andy Galpin: You don't have to cycle it because there's no feedback loop here. It's just an amino acid.

Rhonda Patrick: Okay.

Andy Galpin: So there's no, like, creatine, like, you're not shutting down any endogenous process by doing it. But we will tend to bring it away just from—if we don't have a particular purpose with supplements, we don't take them. It's like, for that purpose alone, we're like, okay, great, we finished, we competed, we did something, we're pulling it back down. So for the people who are not in competitive sports, we will tend to just use it when we have a bigger priority or we're training really hard, and so we use it in six to ten weeks. And then if you want to, like, come off of it, but you don't have to cycle it. We have some people that are on it permanently, and they just don't come off of it. I haven't seen anything to suggest that you need to pull it away if you don't want. And it's pretty safe.

Rhonda Patrick: He said it's been well studied.

Andy Galpin: Super well studied. I haven't seen—outside of the acute tingling, I can't say I've seen any side effects that have been documented that are a problem. So again, it's amino acids, it's pretty straightforward.

Rhonda Patrick: So anything else that we didn't talk about? The creatine dose, I mean—typically, I mean, like I said, Darren Kando just was on the podcast and talked about typically for muscles like 5 grams, but reasons to go up for cognitive?

Andy Galpin: Yeah. I mean, Darren's published so much in this world. We don't use the 5-gram number at all, for the most part. As I've said a couple of times now, it's because we deal with humans that are literally triple the size of each other.

Rhonda Patrick: A 0.1 gram per kilogram body weight is what I think he said.

Andy Galpin: Exactly right, which translates to a lot of people as like 3 to 5 grams, right? We probably spend more of our time at like 7.5 to 12.5 grams most of the time. We'll go as low as 3, no problem there. I'll go 5, no issue there. You want to use 5 as a starting place? Awesome, titrate up from there, really no downside of going higher. So we will go quite a bit higher quite often. Darren's actually done some stuff at 20 grams a day for years. So as long as you're not getting—nausea is like the number one thing we get: I got nauseous, okay, great. So if you're not getting that, then we run that train pretty high pretty often.

Rhonda Patrick: People get GI distress. Some people get that. I don't.

Andy Galpin: Yeah, yeah, yeah.

Rhonda Patrick: Any other supplements?

Andy Galpin: Well, you mentioned quickly, I think it's probably worth sodium bicarbonate.

Rhonda Patrick: Yeah, okay.

Andy Galpin: Same idea, different mechanism, but same idea as beta alanine. So sodium bicarbonate, you're making yourself more alkaline, right? That's all you're doing. So if you don't like beta alanine or don't want to use it or something like that, you can go the sodium bicarbonate route. That is—you can get that at the cheapest price possible, baking soda, right? You can literally do that. We have done that many, many, many times, just take baking soda, put it in water, and drink it. Way, again, many, many years ago—it's a little bit off-color—but when we would have to run these studies with sodium bicarbonate, we would have to do it really close to the toilet, because this will have a very pronounced acute GI effect on you. And so there were many times of wheeling over carts when you have like an IV in somebody or something, you're like, get them over the toilet—not a good situation. So, because of that, most people have modified the delivery mechanisms of sodium bicarbonate, but it does work pretty well. If you're concerned about that, you're like, that is the least appealing thing I've ever heard in a podcast in my life, you can just use creams. Momentus makes PR lotion—that's exactly what PR lotion is. It's just a sodium bicarbonate cream. So this is local. So if you're using your arms today, you can put it on your arms, and you don't have to put it through your GI tract at all. You can put it on your quad or whatever you're doing. So that is the best workaround.

Rhonda Patrick: And that improves your high-intensity performance?

Andy Galpin: Yeah, sodium. You're putting sodium directly intracellular as well as it'll get into blood flow.

Rhonda Patrick: But does this—this doesn't take weeks like beta alanine.

Andy Galpin: It's an acute effect, yep. So you rub it on right before, or you take it right before—30 to 60 minutes before training would be what you're looking for. Takes some time to get in and get into tissue, but yeah, this is an acute effect, and this is definitely something I would generally only use on training days. Where beta alanine you could take, and probably should take, on non-training days because it takes a while for that storage to come up. Creatine, same thing. If you're gonna use a sodium bicarbonate or equivalent, this is only like a pre-workout strategy.

Rhonda Patrick: I want to get into recovery and some other things, but taurine—have you ever messed around with taurine? It comes to my mind. I've come across the literature. Also, my late mentor Bruce Ames called it a longevity vitamin, so he was taking a gram a day, and this was for longevity reasons, and there's a lot of evidence for longevity. But I remember when I was looking into it, I was coming across some performance stuff. It seemed a little mixed, but I was kind of curious.

Andy Galpin: We don't use it.

Rhonda Patrick: No. Okay. It's good for mitochondrial health, but again, more longevity, I think, than performance-wise.

Andy Galpin: The closest you'll see is this will come in a lot of pre-workout cocktails.

Rhonda Patrick: What do you think of those?

Andy Galpin: Okay, I prefer people having the least amount of artificial ingredients as possible. That's our default position, right? If you want to use a stimulant, we'd rather you use coffee, tea, so on and so forth, right? If you're going to use a pre-workout combination, the major downsides are we can't control dosage of individual ingredients. For most of our people, that's a problem. For me, as a scientist, I hate it. I want to know what we're dosing. We're going to run experiments, we're going to try things out, and when we have a pre-made cocktail, I don't have any influence on what we're tinkering with. I like precision, I like detail, I don't like the fact that we have a whole bunch of things coming in that we don't know. I don't actually know what's in there, I don't know that they're dosed at that level—there's all these variables that we don't like. I'm also not ultra concerned that if somebody really wants to have a fill-in-the-blank drink before they train, and that makes them train harder and better, all right, we can live with that. I can handle that if that's your one thing we're dealing with, but if it's up to me, we're not going to use them. You'll never see me program one of them, ever. If someone already has it and they're going to fight against it, okay, I might let that slide, but it's never going to come out of my mouth.

Rhonda Patrick: I don't like them because it's like, it might have one or two compounds that I'm interested in, but then it has a whole host of things that I don't want. And it's like, I can never find something that doesn't have something I don't want. Speaking of which, supplements that we don't want to take—I mean, I don't know if there's ones that actually inhibit performance, but I'm interested in the ones that are blunting adaptations. Maybe we can talk a little bit about—are there ones that are actually, you don't want to take for performance as well?

Andy Galpin: Caffeine. If you go too high on caffeine, you'll actually see performance decrements—like endurance performance decrements—way high. Like that stuff, like I said earlier, eight to ten grams per kilogram, you'll start to see performance come down.

Rhonda Patrick: That's way insane. I mean, you'd have to be taking some kind of powder or something.

Andy Galpin: Yep.

Rhonda Patrick: Yeah, yeah, yeah.

Andy Galpin: So you'd be drinking—

Rhonda Patrick: Okay, so high-dose caffeine would be something that's going to impair performance.

Andy Galpin: Of course, you could—like some people live at that level, so they'll be fine there. But yeah, that's one of them. I think what you're probably referring to is things like copious and excessive amounts of supplemental antioxidants, right? Antioxidants, anti-inflammatories, absolutely. The lab I was in as a graduate student did some of that original work on acetaminophen and things like that, so I was around for a lot of those programs. And then stuff came out on specifically things like vitamin C combined with vitamin E. Vitamin C in general, vitamin E—we want to default to food. If we can get it from there, we do. That's where we're looking for all of our nutrients. Clear evidence, in my opinion, at this point that antioxidant consumption from food has no detrimental effect on exercise adaptation. Eat your blueberries to your heart's content, right? Eat the cherries, eat whatever you want. Never seen evidence to suggest that will blunt performance. There is some evidence to suggest though when you take those as a supplement—

Rhonda Patrick: Vitamin C, vitamin E—but are they always combined? Have you seen a vitamin C by itself, blunting—like, and what dose, if you have?

Andy Galpin: It's a great question.

Rhonda Patrick: I know I've seen a lot of combi—vitamin E is a very powerful antioxidant.

Andy Galpin: Super. It's like getting in your brain.

Rhonda Patrick: Yeah, so I'm always, you know, it's something I'm very interested in because there's definitely a good amount of evidence that taking vitamin C in the dose range above 250 milligrams a day can help prevent some upper respiratory tract infections, particularly in high-volume training endurance athletes.

Andy Galpin: Yeah, we use vitamin C very judiciously—not to get us back there, but you start actually looking at iron, what it does when you co-ingest iron with vitamin C. If you're going to go after iron, you probably should bring vitamin C along. You want to bring in collagen, probably should bring in vitamin C—super lower dosage, like 50 milligrams, right, like way down. You want to actually start doing anything to prevent someone getting sick when they're traveling. Again, especially when they're traveling in a six- to eight-week hypercaloric state, and they're going to be on a plane, and then they're meeting, greeting, and there are fans. Okay, we're certainly going to go for any kind of immune support that we can have. I do not hesitate to go to a gram of vitamin C. You can go way up there for three days, five days, seven days, two weeks, whatever the case is—not super concerned about that. We're not going to live at that level. Five hundred milligrams of vitamin C is a very reasonable dose.

Rhonda Patrick: So do you think the timing of it—let's say someone works out in the morning, and they take their vitamin C with dinner?

Andy Galpin: What do you think a half-life is on 500 milligrams of vitamin C?

Rhonda Patrick: It's not very long.

Andy Galpin: No, it's going to be pretty transient.

Rhonda Patrick: It's like a couple hours in the plasma. I bring that up because—

Andy Galpin: Right?

Rhonda Patrick: I don't know the answer, right? I'm just—what I'm interested in is, okay, so you know a lot about adaptations in terms of muscle adaptations. There's the cardiovascular adaptations, there's neural adaptations, right, that are happening as a consequence to the inflammation and the oxidation that we are causing from exercise that are important in those adaptations. And so you're not wanting to blunt those oxidants and inflammatory signals that you're making. So here's the case I'm trying to make: I don't think people should be supplementing with anything above the RDA for vitamin E, alpha-tocopherol in general, it's just you don't need 400 IUs of alpha-tocopherol. But all these studies that are coupling vitamin C with the vitamin E, it's like, hmm, are we seeing this because the vitamin E was there? I think there was maybe one study I recall; I have a topic page on vitamin C, and I think it's on that topic page, and it was maybe 500 milligrams, maybe it was a gram, I don't know. But I just—again, it's like, it's good to know because, for one, I like to take high-dose vitamin C when I've been exposed or when my son's been exposed—it helps me. And so it'd be nice to know for athletes as well. It's like, okay, can I take that high-dose vitamin C at a certain time—

Andy Galpin: I don't even remember the last time we recommended vitamin E to anybody. So we rarely dose it for all those reasons. The reason I asked you the half-life question was I was thinking the same thing. I don't know anybody that's actually run any even light trial on timing of vitamin C for exercise adaptations. So I don't know if you took it later in the day and you trained, took it 12 hours away—I don't know that it would have a different effect. It may, it could. To answer your question, here's how we handle vitamin C. We're not just giving it to people. It's not like a standard thing like magnesium or omega-3. We will use it judiciously in different things, but I'm also—I'm not worried about it. If you ask me what am I concerned more about, the small amount of adaptation that I miss versus not being sick, that's an easy exchange for me. Categorically, here's how we think about it—and again, athlete or non-athlete, it doesn't actually matter. There are times when we're trying to induce adaptation. When we're doing that, we're going to want to let those stress things happen. And then there are times when we're trying to peak. We call this optimization versus peaking. If I'm peaking, I don't care about adaptation, I'm trying to maximize performance in the short term. In that case, we are going way up on antioxidants, we're going way up on vitamin C. Don't want to get sick, want you to feel great, we want you to perform at your best right now. If that compromises some adaptation, fine, I don't care, because we're trying to get the max performance right now. If we're concerned about long-term optimization, I can't emphasize this enough: even in people who are not competing, this is still a thing you should play with throughout the year. You should have phases of optimization, you should have phases of adaptation, you should be pushing this boundary. If not, you're going to kind of run medium all the time. And so that's how we will—I will have no problem putting it there. If we have some reason to think somebody is in a really high oxidative state because of really poor nutrition, environmental exposures, any number of other things, then we might just kind of prophylactically give them vitamin C. Probably at 500 milligrams. I'm not worried about that. I'm not super concerned.

Adaptation attenuation, it's not blocking. It doesn't mean you're getting zero. It's you're getting 5% less, 10% less. Like some amount that matters, but it's not zero. It's not like absolutely zero. Oh, I did nothing. Like, no, it just means you got 90% of where we thought we could have got potentially.

Rhonda Patrick: Yeah, it would matter if it's every day. Maybe you're getting 5% less over 20 years. Right. But, you know, the way I, so if I remember correctly, and, you know, people can go to my vitamin C topic page on my website and see there's like, we have a graph. Your plasma levels peak, and then it goes pretty close back to baseline. I would say after like three hours or so. So if I'm taking it, I'm taking mine at night. And I'm all night, I'm sleeping. And so it's like, when I work out in the morning, my level should be normal by then. But that's kind of the way I approach it. Anti-inflammatories, you know, how do you feel about people taking things like NSAIDs for, you know, pain or as an anti-inflammatory if they're working out too hard? Because that also blunts adaptations, right?

Andy Galpin: Yes. Yeah, it can. It's the same, like you're running a calculus, right? Like, what are we trying? What are we worried about? Should you take them every day? Probably not for many reasons. Not a good approach. My wife actually just started a new training phase a couple of days ago. So she added a couple of new exercises she hadn't been doing. And she tends to do this, just went way too heavy. So much pain. She has not been able to move for two days. Like, bad, right? She's just like, can't move without really, really substantial amount. I couldn't make my heart happier. Like, I love hearing her in physical pain. Just makes my joy there. Because she's not like hurt, you know, she's just like, oh my God. The kids are just terrorizing her. They're just like wanting to play with mom. And she's just like, everything hurts on my body. Yeah, we're like, she's using a lot of NSAIDs, right? Like, there's no win here. There's no positive benefit. There's no adaptation we're missing with you being in extraordinary amounts of pain, right? In those particular cases, when you overshoot it or whatever happens, yeah, like use them, no problem. If that's what you're using just to get through your training, then our training program is probably, or something else in our physiological process is depleting our recovery bucket. And we need to go fix that problem. So if it is something we have to use, the exceptions there are our athletes, of course. Football is really hard sport. And if you got to take it to get through a football week, because that's your job, then like that's what we're going to do. And there's some other things there. But for most people, yeah, we're not using them very often.

Rhonda Patrick: Right.

Andy Galpin: I like the look on your face, by the way, when I said my wife is in so much pain, it brings my heart joy. You're like not smiling at me at all.

Rhonda Patrick: Well, I'm just wondering what she did to be in that much pain.

Andy Galpin: Nothing crazy. Just like she normally does a bunch of her training at home. And then she was actually happened to be at a gym where it had some other equipment. And she's able to be like to load stuff more. And she was like just too happy at the moment. It's like, yeah. So she's doing some deadlifts, some RDLs. I think she did some overhead pressing, some lat pull downs. Like not crazy stuff.

Rhonda Patrick: I love being sore too. I mean, I love waking up the next day and... It's great. Oh, it's the best. It's the best. Recovery. Recovery. Let's start with some supplements for recovery, but we're going to get into recovery as well. I hear a lot about... People have been asking me a lot about tart cherry juice, which when they're asking me about that, I was like, oh, you mean for sleep? Yeah, because I'm so used to like people taking tart cherry juice for sleep. But apparently it's being promoted for reducing delayed onset muscle soreness, recovery. So can you talk a little bit about...

Andy Galpin: Yeah, there's data there, there's data there to support muscle soreness, muscle damage. Could I make a strong argument that you wouldn't get the same thing if you just had a really high similar food source? I think you could, actually. I don't think there's anything magic to that. Not surprised, right? If you think about what's in dark, rich colored fruits. Polyphenols. Right. Like we know that that's there. It's the same thing we make when people talk about like blueberries for cognitive performance. Yeah. It's also the same probably in strawberries and probably in raspberry. Like it's not like magic to the cherry or the blueberry. I don't think it is a super high concentration of polyphenols in a bunch of different areas that's probably doing most of the work here. But yeah, you will see that there. We tinkered with it for a few years. We don't use it very much, honestly.

Rhonda Patrick: Typically, you know, when I have delayed onset muscle soreness or DOMS, I go for a run and I'm good. I mean, it hurts when I start running, and then as I'm going throughout the run, I start to feel better, and then the next day I'm much better. So, you know, I'm just wondering, is tart cherry juice something you think I should try experimenting with, or...

Andy Galpin: Probably not if you're not getting that sort of often. Then who's the kind of target person that may benefit from tart cherry juice or your blueberry polyphenol supplement or your polyphenol booster supplement, whatever, fill in the blank? What dose? Yeah, again, we don't use it very often. So I'm probably not the person to make the case for people wanting to go out and try it. It's cool. It's fine. Again, the research is there. I've seen it. It's compelling. You also mentioned sleep. That's another compelling reason. So if you're wanting to use kind of a double combo and you like it for sleep, where this is most popular is in the bodybuilding communities for those exact reasons. So I can take it a ton at night. It'll help me sleep and I'll be a little bit less sore. I'm kind of getting a double win.

Rhonda Patrick: Is that because of the melatonin in it that's sleep or combination of polyphenols?

Andy Galpin: Plausible. Probably all of the above, right? And again, that research is actually there. You'll see it. And I have seen a lot of people who will anecdotally say, yeah, it helped my sleep a ton. But again, I probably haven't recommended it in five years or more. We kind of did it a bunch. Okay, great.

Rhonda Patrick: Yeah, I've had multiple people asking me about it. And so finally I was like, okay, what is this?

Andy Galpin: We generally don't honestly favor recovery supplements that much. That's just like probably the bigger answer here is supplements for recovery is not that great.

Rhonda Patrick: It's not as good as other things that we're going to hopefully discuss in a minute. What about glutamine?

Andy Galpin: Yeah, you can do that. So we will use glutamine — conditional amino acid, right? So in our populations when amino acid need is really high, again, you're combining it with caloric reduction and you don't have that much room to go. Like, I just can't give you more food. I can't give you more chicken breast. I can't give you more turkey or elk or whatever we're doing. Okay, fine. So we have some argument for the conditional actually coming into practice with those people. Then you have the kind of area of glutamine with gut health stuff, and then we actually see that a little bit transfer over to even brain health and specifically like post-concussion protocols. That whole line then starts to come together and you go, okay, for our population, there's one, two, and three likelihood of all that stuff. Okay, pretty reasonable. Add on top of that safety profile, no real downsides here. We're not worried about any other effect of it. Yeah, we use it quite a bit actually.

Rhonda Patrick: I have a few thoughts on glutamine. One, that's interesting, TBI, because glutamine, it gets converted into, you know, it gets used by mitochondria as well as a source of energy. And in fact, I did a lot of research in graduate school with glutamine and T cells and activated T cells. And this is kind of where I got into this. I now take glutamine for immune reasons and I don't know if you've seen any of the literature on long endurance athletes, you know, taking glutamine.

Andy Galpin: Yes.

Rhonda Patrick: If there's an exposure, I'll take it three times a day. So if my son all of a sudden starts sneezing, I'm like, okay, you're just scooping. But so glutamine is used by activated T cells. And it just dawned on me. I'd done all this research. I'm like, you can take glucose out of a cell culture as long as there's glutamine there, those cells are fine. They are fine because they consume glutamine as an energy source. It's used as, you know, alpha-ketoglutarate. So basically it gets converted into that. But I started taking it. And this is total anecdata. But, you know, for a long period of time, I never got sick. Then I became a mom. I still didn't get sick until my son started school. And then it was like insane how often I was getting sick. I was like, I was wondering if I had cancer. I'm like, what is wrong with me? And then I started the glutamine. And I don't ever get sick anymore. I'm serious. Now, I'm sure if the flu came up or something like that, I probably would get it. But upper respiratory tract infections, like if I get a little bit of anything, it's a tiny bit of a runny nose for like a couple of days. And I haven't been sick in months. And that's unusual as a parent, as you know.

Andy Galpin: Oh, my God.

Rhonda Patrick: So that's why I take it. I take it not for recovery reasons, but I take it prophylactically every day. Right now I take about six grams a day. If I have any inkling suspicion that it's coming, I'll bump it to 20 grams. The only downside for me is I can get a little gas when I start increasing my dose. I think you mentioned no downsides. I'd say the only downside is if someone has cancer, like colon cancer or liver cancer. Cancer cells like glutamine. I was talking about T cells, but cancer cells can thrive with glutamine. It's an energy source. And people don't realize that. And so I was thinking about the TBI thing that I'm totally going on off a tangent here, but I'm wondering if the TBI thing, if there's an energy component to it.

Andy Galpin: Oh, no, there absolutely is. There's huge. I covered this. I did a whole... We published a paper a few months ago. Myself, Tommy Wood, and Federica Conte, who works with me at Parker now as my research scientist, we published a review on preventative as well as post-brain injury concussion, all the supplementation, dosage, timing, all that stuff, as well as whole food equivalents. And that whole paper is open access. So you can go through that whole thing. But yeah, this came out as a pretty clear one. When you start then poking around into the gut health literature as well, you start going, oh, okay. The immune stuff you just brought up, this is such a clear connection between this entire chain from being sick to the brain health to the energy. You pay attention to how it's working, what it's doing. You're like, okay, this is one of those times where it lines up and you go, oh, yeah, now I get it. This is why it's having such cross benefit.

Rhonda Patrick: Right. Absolutely makes sense. In the gut, too. It's being converted to energy. Your gut cells are using alpha-ketoglutarate. I mean, it's so interesting. I think there's so much to be discovered with glutamine that I hope people are going to research that more.

Andy Galpin: We do almost always 10 grams twice a day, morning and night. Like that's a pretty thing, especially if we have any inclination or direct evidence of actual gut issues. That's a common one. If we want to drop it then back down to 10 grams total a day, we will do that. But we will generally live at least 10 grams a day. That said, I'm going to do this. I'm going to do your protocol because I'm on it. And if I ever get sick again, I'm having a lawyer send a letter to you. I'm playing. I'm everybody.

Rhonda Patrick: I gave it to my son as well, and he's not getting sick like nearly as much. It's real. So I was thinking it was placebo. I was like, oh, it could be placebo because, you know, honestly, if it was placebo, I don't care if it works, it works. But my son doesn't know that I'm giving him glutamine. I'm giving him almost five grams. And it's been a pretty night and day difference in terms of bringing illness into our house, not getting a cold. This season has been unbelievable. And it's funny because this season has been the worst for all of my friends. Like everyone's been sick. We haven't.

Andy Galpin: My wife probably has had one cold in a decade. It doesn't matter. You could soak her in a bath of 16 cold viruses. She will get nothing. My daughter is like okay, but she gets a lot. My son and I just, you bring it home, it's over. Like it's a wrap. I'm so done. And I get so mad because I'm like, I knew all these things. I do this, whatever. This is my job. But I've never tried this at this level. I'm so, like, I'm fired up.

Rhonda Patrick: I put it in my coffee or my tea. And the coffee, if you put like monk fruit or stevia, you won't taste it, but it does have a taste. I'm a straight shooter. We just put it in water and down it. It's easy enough.

Andy Galpin: And we just dose it with all the rest. It's like put creatine, put it all in there. Deal with six ounces of the light and just get it out.

Rhonda Patrick: Now what's it supposed to do for muscle recovery?

Andy Galpin: Well, if it has that conditional effect, if it has any of the immune effect, it's going to have the same there. So you'll see muscle soreness as the primary outcome to pay attention to there. Like, is it doing anything anabolically in cachexia maybe, or some other situations, sarcopenic. But for normal people, now why we do it is the other stuff, for the most part, like all the gut health.

Rhonda Patrick: I just wonder how much of the glutamine you're taking in is going as an amino acid versus the energy source. So you're not really big on recovery supplements. I've got two more to ask you about. One is hydrolyzed collagen powder for joints and tendons. And this is where I get into, you know, it's high in arginine. It's actually really high in arginine. I take it mostly for skin because I've been pretty convinced by the skin data. But I was, you know, what are your thoughts on...

Andy Galpin: I've changed my tune on this one. I was not compelled by this evidence for a long time. I was also not compelled that as long as your protein intake, whole food, is high or higher than basic numbers, there's not really a compelling evidence. I don't care about skin, so I'm like, whatever. I've changed a little bit. More and more research has come out and it looks like there's something actually happening here. Where this gets sticky is still the argument of organ-specific conversion. So if you are consuming it, how do we actually know that you're consuming collagen and that's getting into collagen? Well, the argument would be if it's all being broken down into its individual constituents, then it doesn't matter. And then there's some talk of like, well, there are these special kind of conditional ones where it gets crossed through as these combination of amino acids. So therefore it's going to be more targeting collagen. We'll wait and see if that holds true or not. I'm not entirely convinced of that either. But that said, when you go to the end of the story, it does seem to be doing stuff for connective tissue and ligaments.

Rhonda Patrick: The study that convinced me of that very question that you were asking was actually published a while ago, over a decade ago. And it was an animal study where hydrolyzed collagen powder was radiolabeled, and intact peptides were making their ways to the tendons. And I was like, okay, I mean, yeah, it's a rodent, but are we really going to say that an intact peptide is going to make its way to the tendons? I mean, maybe, maybe it's not going to happen in a human, but it seems encouraging.

Andy Galpin: I think this is an area where we probably don't have the answers yet. It may be something else. Maybe it's that, maybe it's not that, but something's happening here. And so now we will very often recommend it prophylactically, even if you're not injured. Certainly if you have any soft tissue injury history, you're compelled to that. Thirty to sixty minutes pre-exercise seems to be the time. So timing, dosage, does seem to matter with collagen. I mentioned earlier co-ingested with like 50 milligrams of vitamin C seems to be the thing. This is all Keith Barr's work, among many others, but he's the one who's pushed this for many, many years now scientifically. So he gets credit for a lot of this work. And again, I was on the other side of the fence. I don't buy it, I don't buy it. It's got a very different amino acid profile than protein though, completely different. Proline and hydroxyproline. Yeah, I mean, that was the argument against it for many years. Well, for muscle, yeah, but like for connective tissue, now it appears potentially it mattered, right? So, yep, we'll do it. As you've heard me say many times now, I also like to run like, well, what ifs? Like, what's the downside? There doesn't seem to be really any downside here. So cost, money, sure. Physiologically, we're not blocking adaptations, we're not shuttling something else out. We're not doing long-term damage, we're not shutting off a pathway. Okay, worst, we spent some money. All right. Most of the people I'm around, they'll take that exchange. Then you start adding with something like collagen, hair, skin, other potential benefits, like, okay, I'm getting potential benefits in multiple areas. There is some human research on this. It might work. Very little downside. Yes, it's pretty cost-intensive relative to protein powder. And if that's your barrier, fine, I get it. No problem. But for the most part, it's not that expensive. Reasonable. There's enough competition now that you can find quality brands.

Rhonda Patrick: What are your thoughts on glucosamine chondroitin for tendon joint?

Andy Galpin: We don't use it much. Honestly, I would have to dive back into that database. I haven't looked in many years. It's kind of mixed evidence as far as I last saw. Sometimes I'll, like, if I have an issue, it's like, okay, let's try to throw it in the bucket. I don't see a big downside, just in case. I give it to my dogs, if that makes you feel any better. But that's the only thing we give them. They're old. But yeah, we don't use it. I think there's more compelling ways to go about it. If we're having consistent injury issues, we're doing other things. That's not going to be our first, second, or third line of defense at all. Yeah. Okay, well, we'll hopefully get into some of that becau

Rhonda Patrick: Because I want to get into recovery. This is an area where it's very important as, of course, you know, but I don't know that a lot of people focus on recovery. Although it's becoming, I think, more increasing. It's more awareness is, I think, being generated now. But I was thinking maybe you could kind of just start by walking people through the physiological process of what's going on during recovery. Why is it so important?

Andy Galpin: How are you defining recovery? How are you labeling?

Rhonda Patrick: I guess, you know, you're talking about the shifts in inflammation and immune response and cellular repair, all the things that are happening in response to the workload that you've applied and the inflammation that you've generated and the, you know, oxidation that you've generated.

Andy Galpin: Okay. The reason I ask that is because we answer this differently depending on how people are thinking of recovery. We think about this in terms like a muscle soreness, or we think about this in terms of my energy is low the next day, or we think about this in terms of I felt fine, but my actual performance was just a little bit lower. Those are three different types of recovery. Are we thinking about this more chronically? Man, I've just been going down for several weeks and several months. Like, depending on how we frame this, my answer would be completely different. So is there one or more of those that you would want to focus on?

Rhonda Patrick: I think I'm thinking more about adaptations that are occurring to improve muscle mass and strength and your cardiorespiratory fitness, for example.

Andy Galpin: Yeah. Okay. So in that particular case, you've laid out the basic framework for us a second ago, right? In terms of the three big processes that happen there. It is not the case typically where you're actually tearing tissue down. In the case of strength training and muscle, we hear that all the time. Like you break the muscle down, you have these micro tears that would then have those cascades you're mentioning. That actually doesn't happen as much as people think. Most of the time muscle tissue is fine. We're certainly not tearing down a lot of tissue in our cardiovascular system. This is more of a signaling issue than it is a damage issue. And we know that because you can induce those same adaptations if you cut those first parts of the equation out. So I can give you things that simply ramp up adaptation that don't require damage at all. I do not have to have inflammation to induce adaptation. That is the primary signal though. Same token, if I give you an inflammatory agent without any tissue damage at all, I can get similar adaptation, right? So we can cause physiological responses with an inflammatory marker that comes in rather than an actual tissue damage. So those things are independent of itself. It's not there. But you laid out the basic cascade, some sort of inflammatory immune response there, some sort of tissue edema, swelling, and then some sort of back cascade. Why supplements? Why different tools? Why different recovery protocols work and why they matter is because they can target any aspect of that. The front side or the back side. The insult coming in or the adaptive response. And you can play a game any part of that area. We will use different solutions based on why we think that the thing happened in the first place. So that is our overall framework of how we set up like recovery in this context.

Rhonda Patrick: Okay, so then let's take a step forward and talk a little bit about what you were asking me. And that would be like, how can a person, an athlete sort of know if they… What can they… What metrics can they look at to help signal if they are… if they're helping, if they're normally sort of recovering from their training versus not… so then muscle soreness, the injury, like what sort of metrics?

Andy Galpin: First, most important metric is how are you feeling? And I'm saying this because if you look at actually the data, and we've done this across millions of data points, like literally millions of heart rate variability data points and things like that. Subjective perception, how you feel today, will stack up as tight as almost any other biological metric we can pick. It's really, really important. If you're feeling good, if you're making progress and you don't feel terrible, then I'm not worried about your recovery at all. Like, we're done equation. So when you ask me, what should people measure? Most of the time, the answer is nothing. Don't worry about it. You making progress? Yeah. You're in a lot of pain and suffering? No. Good. We're done. Like, you want to do metric behind that. Sometimes it makes things worse. Like you sometimes we're looking at data and it's not the right way to go about it, and that can cause problems. We end up pulling technologies away from people a lot. We pull sleep trackers away from people a lot. We do those things. So I'm bringing that up because that is the metric you should care about. Progress and pain. We're good on both of those. We're done. Like, this is the only recovery equation we're happening.

Rhonda Patrick: Okay, so let's say you have muscle soreness again. We're back to the muscle soreness.

Andy Galpin: Easy. No problem. Muscles are sore. Step number one, input. What's your training program look like? I told you the story earlier. Wife getting super sore. That was her dumb, dumb fault. Like she did a training boo-boo, as she calls them. And okay, great. That's not something we have to go fix. That was just like, all right, like don't do that again. Or suffer. Let's just throw that one out. Let's go to the backside. Let's assume your training program is good. And just for the sake of speedy conversation here, let's assume sleep and nutrition and mental health and all that is okay. Right? Because that is all going to be part of our real equation. Let's go to the end of it. What do you do? Got super sore. How do you fix it? Supplements again would not be our route. If you need to take pain relievers because you're there, fine. What's going to be more effective? Now you're actually starting to talk about things like blood movement. You actually mentioned earlier, you like to move. A low level of physical activity in terms of magnitude of effect is almost always going to be your biggest impact. Can you get something? Can you get out and move a little bit? Thermal stress is another big favorite of mine. Sauna. Great. I like direct contact though. So if we can get in warm water, I prefer that. So this is jacuzzi, bath, things like that. If you want to go to… and we've run a couple of actually DOM studies, two of them using Normatec boots, right? And compression boots, air boots, like things that go there. That is fine as well. We've done a muscle stimulation stuff. So, yeah, muscle stim units and things like that. You'll find data that supports all of those things. If you want to sledgehammer things and use a combination, we will do that too. We will say, okay, great, we're going to bath today, we're going to do Normatec boots, we're going to do hyper ice stuff, we're going to do compression stuff. You can do all of these things. They probably are working on similar mechanisms, but again, no downside. And if you're in that much pain and suffering, use them all. Like really try to use everything. Because what you're basically doing is you're doing low level physical activity for many, many, many hours of the day. We'll use Firefly, that little tiny device you can put on the front of your leg. It's a little strip, makes your toe bing, bing, kind of up, down, move. You can do it for hours a day. So you can put that thing on, you're on a plane, you're working, your toe and your foot is flexing at a high frequency, right, dun dun throughout the day. That's been shown a bunch of times to be super effective for recovery. So there's tons of little tools we can do, but all of it is basically doing the same thing. It's low level blood flow for a long period of time. So pick your tool, pick your poison. You want free, you want expensive, you want combinations. I can give them all to you. But it's all, again, basically the same thing.

Rhonda Patrick: So the level of blood flow, and you're saying for a long period of time. So what I'm doing is short, I'm doing, you know, 30-minute run. What's going on here? Is it delivering just oxygen and nutrients and inflammatory things are going to the right tissues? Like, or what, what's the mechanism there?

Andy Galpin: All of the above. All of the above. I would have bet too, after you do your run, you're probably a little more physically active because you're not as sore. So you're probably going to be walking a little bit more. You're going to be doing things more active throughout the day. So your 30-minute run is still getting net on aggregate, get a lot more blood flow. Yeah, more blood flow in, more nutrients in, more waste products out, all of the above. You also have indirect signaling. A lot of pain, to go back a little bit, a lot of muscle soreness pain is neurological. So you have pressure likely happening on the nerve endings in that specific area. So you can get some of that fluid out of there. You have less pressure, you have less pain receptors. You also have desensitization that's happening. So you're moving in sodium potassium pumps on the cell membrane. That's moving stuff back and forth. We're seeing adaptation there. So it's going to be a combination of all that. I don't know if I've ever seen any particular set of papers that say this is the exact molecule signaling property that is explaining all of muscle soreness. So the best answer we could say would be all of those things are likely contributing on some level. At the end of the day, most of the time exercise-induced muscle soreness is a cellular pressure issue. And so the more that you can get that out there, you have to get the inflammatory signal out of there because that's going to keep putting you back into tissue swelling. So get the fluid out and then stop the signal that says stop putting more tissue or fluid in there. And then eventually you're going to get yourself back to normal.

Rhonda Patrick: What do you do if someone's feeling a soreness that isn't necessarily going away? It's kind of sticking around. It's not like a really bad injury kind of thing, but it's enough to affect their performance. It's enough that it's like there's something going on. Now this like compression thing, I've kind of been experimenting around with it. Voodoo floss, the Voodoo floss. So I guess it's blood flow restriction. And you wrap it around something. Like for me, I've got like this forearm thing. It's like the tiny tendons or something. And it really is when I'm pulling.

Andy Galpin: Yeah, you're probably actually looking more of a fascial issue than you are blood flow. That's what the Voodoo floss stuff is going to do. So you're pinning and twisting and moving. So your connective tissue glide and slide. So your connective tissue is supposed to glide actually. So people don't actually realize this very often. But you should be able to pinch your skin and pull it away from your tissue. That's not just fat there. If you are pinned down constantly, that's a connective tissue fascial issue. And so what you're doing with that is you're rubbing it both horizontally and vertically. When we typically think about like massage, it is a vertical compression, right? I'm pushing down on the tissue, I'm down on the tissue. What you'll see often more benefit is actually horizontal movement and pulling away. This is if you've ever seen like cupping, people do that. You're pulling skin away from fascia rather than smashing fascia back into it when it's kind of knotted down already. So any relief you're getting there is not probably for the blood flow. It's the fact that you're pinning that fascia and then you're moving the tissue around the fascia and getting that kink, if you will, to let go. So completely different mechanism of action there. That is acute and chronic, but mostly that is an acute issue. If you're dealing with things like runners will get a lot of like side leg pain, TFL pain, IT band, a lot of times same issue there, right? So like you're getting more glide and slide, that fascia can move appropriately, and that's where the pain signal is going. People don't realize that there's a load of nerve endings in fascia. There's a ton. So if that stuff gets irritated and aggravated, that's going to be pain. And that's probably not a muscle issue. You might not necessarily be able to tell. A lot of people can't tell their fascia versus their muscle, but more likely than not, it's connected tissue fascia issue.

Rhonda Patrick: And what is the best way for fascia? Is it something like a voodoo floss?

Andy Galpin: You can. Conceptually, you just want to move it. So if voodoo floss does it for you, awesome. If you want to roll out on a lacrosse ball, cool. If you want manual massage, great. Cupping, infinite ways to do it, but what you want to do, again, is not just compress. The only thing traditional like a foam roller or any other self-myofascial release, generally people are smashing down. What we want to think is actually pulling away. So pulling the fascia away from your body rather than smashing it into the muscle, and then rotating it, moving it horizontally, gliding up and down versus just smashing together.

Rhonda Patrick: So the compression thing that you were talking about with the boots? So that's working through blood flow restriction, and then how's that working?

Andy Galpin: So there's a whole host of companies that make this. Normatec is the one that's been on the market for a long time. It actually recently got acquired by Hyperice. But these are boots that you can sit in. They make them for the upper body too, but you can sit in them and imagine a pair of pants, and the pair of pants inflates with air all the way around it. And so it goes on, it inflates, entire leg gets crushed, and then it deflates. And then it gets crushed and deflates. So it squeezes back and forth and back and forth. So you get a little bit of hypoxia, a little bit of blood flow. A little bit of hypoxia, a little bit of blood flow. And they can do it for 20 or 40 or 60 minutes or however long you want. It's basically simulated exercise. It's a little bit of blood, a little bit back. So blood flow, yes. You will actually see really compelling evidence on water immersion. Not only cold water. I simply mean water immersion.

Rhonda Patrick: Yeah. Well, heat, I would say for sure, because you're also increasing blood flow, right?

Andy Galpin: But it's the orthostatic pressure that comes with being in fluid that will do the same thing. This is, again, one of the many reasons why I'm like sauna is not the only answer here. It's great for a thousand things, but the water itself is playing a little bit of a magic role. And we know this because there have been trials where we've actually controlled for temperature and you still get those benefits of just being in that fluid environment. So if you can do that, you can. Gravity changes in the equation, things can move in and out of tissue, and there's actually pressure that comes from being in the water. It's a low level pressure that smashes up against your tissue. Now, if you want to change temperature and you get some of those other benefits, that's great too. Water itself is a fantastic way. So I would strongly also recommend people getting into water if they can.

Rhonda Patrick: Let's talk about that. Let's get into. Okay, so for recovery, you hear… I mean, you know, probably know I'm super into the deliberate heat exposure through also Jacuzzi and sauna. Yeah, there's cold water immersion. I'd love to talk about how… So with, with the heat exposure and Jacuzzi sauna, it sounds like Jacuzzi might be the winner with respect to…

Andy Galpin: It's my personal favorite.

Rhonda Patrick: The orthostatic part of the water as well and helping with blood flow.

Andy Galpin: Yep.

Rhonda Patrick: And also, does it help with the fascial tissue as well?

Andy Galpin: Probably not, mostly just blood flow.

Rhonda Patrick: There has been, you know, some evidence on sauna improving blood pressure, but there's a lot of literature out there on hot baths and jacuzzi doing it. I mean, it's probably a lot more robust, in a way, as well.

Andy Galpin: Yeah, I mean, you have the pressure issue we talked about, and then we have all the other heat-related mechanisms that you've talked about for many, many years now that happen too. So you combine those two, it's a big win.

Rhonda Patrick: And it's not really like, you don't have to worry about the timing as much around exercise. In fact, you can get in a hot jacuzzi or a hot sauna right after you lift weights.

Andy Galpin: In fact, there's some evidence that it's beneficial. It's like supportive. Yeah. We do it a lot. We do it a lot post-exercise.

Rhonda Patrick: Do you do both endurance and weight training, both?

Andy Galpin: Yep. The only thing you got to be careful with is if you did something that you really went over the edge with in terms of training. If you get into a sauna, sometimes it feels like it delays recovery a little bit because it actually kind of feels like it exacerbates the training, like you've continued to train, particularly if you've gone really hard. Like if we've had a… our folks have played like a five hour round of golf in Georgia in August, probably not hopping in the sauna afterwards, right? Because fatigue is high, fluids are already low, so on and so forth. We're not going to add that on. And in that particular case, we're like, walking away. So you got to think through this stuff a little bit more when you're saying, all right, we actually are pretty fatigued, let's not add to that bucket. But like a normal exercise session? Yeah, hop in a sauna, jacuzzi afterwards. We're all, we're all game for it. Totally here.

Rhonda Patrick: What do you… There's a couple of things I want to talk about with the sauna. One, what do you think about some of the, I would still say preliminary at this point, literature on using deliberate heat exposure as a way to improve endurance-like adaptations and improve performance?

Andy Galpin: So here's how we will frame it. It's not a substitute for exercise, of course, but it's better than sitting on the couch for most things. So training's first. If on top of, past that, or we have an injury or fill in the blank there, then we can use sauna to keep maintenance, to keep pace, to keep some cardiovascular adaptation going. So if we're pulling training down, like oftentimes we actually have to pull high intensity exercise down from people. If you're dosing high intensity stuff, like truly high intensity endurance work too often, that can put people in really bad spots. So what we can do sometimes is pull them off of that and insert sauna, and they still can kind of feel like a little bit of, I worked really hard. And some people need that, not for physical reasons, but for other rationale. So we use it in those particular cases. Or we're deloading, or we're doing any number of other things where we can't get as much exercise as we want, or we're bringing it down. So we use it in that particular context. If we then take it into an individual athlete and we're trying to use it for specifically performance benefits gains, I would only be okay doing that if training volume is pretty low. Because anything that takes away from training in an athlete, there has to be a really big payout, because specificity wins.

Andy Galpin: Sometimes that's a good thing. But we've got to be really careful in maintaining always training specificity. In that context, that's how we'll handle that thing. So it would be really time dependent and whatever else is going on in our life.

Rhonda Patrick: Have you seen some of the data? There's only really one human study that I've seen, lots of animal studies, looking at local heat. So on humans, it was the local heat applied and how it prevented disuse atrophy by like 40%. And then there's, of course, tons and tons of animal studies. In fact, I was talking about the animal studies before the human data came out, and I got a lot of pushback for that. But I do think it's, again, in that sense where you can use it on the days where you're not training as much to help with not only the cardiovascular adaptations that you mentioned, but also helping prevent disuse atrophy, right?

Andy Galpin: Yeah. I love heat. It feels good, of course. It feels way better than cold. We rarely have a hard time convincing people to do stuff that involves the heat. It's like, okay, put a hot pad on your leg. All right, I'm in for that one. Hyperice makes a bunch of stuff. I don't have any connection to them at all, but they just make a bunch of little easy things to put on your legs and your arms that get hot really fast. They're super easy to use. So we will do those things, again, quite a bit. Whether or not they're making a benefit in our high-performance athletics, I don't know. But if they're like, that felt good, that's a win. Plausibly helping. Cool.

Rhonda Patrick: Yeah. Well, it sounds like even for recovery, it might. I mean, that's a benefit if it's increasing the blood flow and helping with delayed onset muscle soreness and things like that.

Andy Galpin: Yep. Cold water immersion, on the other hand. Yeah. This is something... It's funny because it's really... It's become popular as a recovery tool. And there's a lot of people that I've spoken to, friends, that didn't know it could blunt adaptations, particularly muscle hypertrophy. Yeah. And they're like, what? I'm getting into it after I lift weights. You finally convinced me to do it, and now you're telling me I'm screwing myself up. Your fault.

Rhonda Patrick: Let's talk about that. Yeah. Muscle soreness, it seems pretty clear based upon the data that is available that cold water immersion is more effective than something like cryotherapy or cold shower. There has been some papers that showed cryotherapy itself did help with muscle soreness, but if you stack them again against the cold water immersion, the water wins. So we really never use cryotherapy. If you're going to use something like a cold shower, then there's other reasons for it. I don't think I would be... I wouldn't put my money on cold showers doing much for muscle soreness. Again, many other reasons why one could do it, but that would not be the primary goal if we're using it for that. So right out the gates. Now it does work, and many studies have been done, and I would say our anecdotal experience, my personal experience, our coaching experiences would support that. Generally, people are going to be a little bit less sore when they go in it.

Andy Galpin: Do we do it immediately post-workout for people trying to grow muscle? No. Many studies now, I feel like every couple of weeks another one comes out, and I'm like, good, good, gracious, we know already. We know already. Stop doing this. Stop doing that work. We know it's not a good idea. The questions that come up then next usually are, okay, so how long post-exercise do I have to wait? No one knows. That's the study they need to do. No one... Yes, like stop doing the basic one. We know that answer. There's like seven studies at least now that have done it. We get it. I don't know, right? If you look at the time course stuff we've done on gene expression, that happens within seconds. Signaling happens within seconds and is ramped up for minutes to hours post-exercise, depending on the marker and thing like that. Gene expression typically peaks three to four to six hours, again, depending on the one you're looking at for muscle and anabolism. Muscle protein synthesis, you're at 48 hours, okay? I know. So like, I don't know, because people always ask, like, what if I lift in the morning and I... I don't know. It's probably better than lifting and immediately getting into your ice bath, but... Probably. Is it four to six hours? Because that's where that number comes from, by the way. It's like all the time course research on gene expression. You're also talking about like four or five genes that were in that study. So it's not like these exact, like, complete mapping of the entire anabolic genetic response. It's like a few of the markers. Some of them are at four, but they weren't all. Some of them peaked at an hour. Some of them peaked like seven hours later. So like the four-hour window thing is like a... It's not exactly what people think it is. So nobody has any idea. Like, I have no idea at all. Again, I'll tell you how we typically handle it, but yeah, we don't know.

Rhonda Patrick: Yeah, let's talk about how you typically handle it. Also, you know, you mentioned when you're talking about adaptations, the different things that are happening. There's the inflammatory response, you know, there's the hormonal responses that are happening. There's a lot of things that are happening, right? And so those things have different time courses. We're talking about muscle protein synthesis, right? You're talking about it's elevated for 48 hours after exercise. And I know I had Luc van Loon on, you know, not long ago, and he's done at least one study, I think two, looking at cold water immersion and muscle protein synthesis. And he was saying, yeah, I mean, you know, because the cold water immersion causes vasoconstriction. So

Andy Galpin: Yep. Have you looked into that literature? Yes. Yeah. Not a ton to go off of there, but yeah, like one can do that. The quick answer there is you're looking at mitochondrial benefits, like which is okay, like then there's some plausible thing there. We don't use cold water immersion a ton. I used to use it more. We do it when we do it, when we do it rather, it's for other reasons. If somebody really overcooks it and they're super sore, great. The other reasons we use it are generally not performance based. We're not using it for longevity or lifespan or anything like that. We tend to use it for things like stress inoculation, for nervous system resilience, for breathing mechanics. That's the rationale we typically go to cold water. That said, we have pulled cold water away from people a lot because there can be serious neurological, not neurological, serious nervous system problems that come with cold water immersion. There can be sleep issues that come with cold water immersion for some people. So in those people, we tend to like back it off because it's a stressor. It's a very big stressor. If your allostatic load is already over the brim, some people cold is great. Some people it is pushing past and making things worse. So we'll wind it back. That said, I love it. I have multiple at my house. I've been doing it for a very long time. I had a deep freezer in the back of my house for many, many, many years that I use. But it's not for everybody. It's not the danger though. It's not going to block all your adaptations. But it's probably not something you have to be doing every day to live a great life either. So lots to say about that.

Rhonda Patrick: So mostly people can use it for their muscle soreness. And other reasons. Presumably, yeah. I mean, a lot of people use it for, like you said, the neurological benefits. I mean, it's something that I, if I use it, I don't use cold water immersion unless it's summer, to be honest. Okay. I know all about the science. My husband uses it. Well, right now he's like, we had to get a new pump, which we got, but then he had to clean it and all this. But he typically uses it every night. He uses it at night, which is funny because a lot of people use it when they wake up in the morning for like that like wake up response and you feel like the norepinephrine, you know, you're feeling focused. And he uses it at night because it helps him sleep, which, you know, I guess the coldness of maybe.

Andy Galpin: A bunch of reasons that you would explain that. So we've actually plotted this. We did a bunch of stuff probably four or five years ago. We didn't publish it. Just we were tinkering around with stuff and we started looking at HRV. We brought it up just in case people aren't aware. It's a marker of overall recovery. We'll kind of keep it at that for now. And when you go into the ice, whether this is anywhere between 30 to 50 degrees for a minute to five minutes, you're generally going to get out of that ice and you will see sympathetic drive, fight or flight is elevated like pretty consistently. That said, we plotted this every 15 minutes for up to three hours post, and you just continually see a rise in parasympathetic drive for up to three hours post. So I don't know when he's using it, but I would be willing to strongly bet he is far more down regulated going to bed when he does the ice for that exact reason. You've got to time it appropriately because, again, when you get in the ice and immediately somewhere between 15 to 30 minutes post ice exposure, you'll be more sympathetically driven. But after that, for several hours, and most of the people, they were far more. And I'm talking about like 20 to 50 percent reductions or elevations rather in HRV, meaning more parasympathetic for many hours. And we stopped actually collecting the data at three hours. So I don't even know how long that that thing lasts. But I'm not surprised. Yeah, we have a non small amount of people like to do it in the evening as well.

Rhonda Patrick: Yeah, interesting. He does it. I mean, it's at least an hour before I'm not surprised at all that he likes it. Yeah, but yeah. Does he shower then before he goes to bed? Is he hot again or does he? Yeah, sometimes he does shower, but it's like a really quick. Yeah, like not. I know that he gets hot. He's actually he's cold in bed, so doesn't really make him hot. There you go. There you go. But he does he does hot tub before getting in the cold. Oh, he likes to get hot first in the cold. He'll get hot and then get in the cold. I hate I do the opposite. I go straight cold. I'm like, I hate going hot. Oh, I don't hate it. But like, I'm like, all right, just get cold. Just like do the cold and get over it. But a lot of people like it that way. I don't really prefer. I don't like doing hot to cold. I get blood pressure changes that are like too much. Yeah, for me, I'm just like, I have to wait a little bit before, especially if I'm like hot tub into the cold. I have to. I've had like some scary times where I'm like, like just I didn't like it. Yeah, yeah, yeah. Understood.

Andy Galpin: Okay, so you were talking a little bit about HRV and that's and you talk about heart rate variability. And I wanted to talk about we were talking, chatting a little bit about this before before we got on camera and for measuring something that people can like, you know, maybe on their wearable device, measure a marker of recovery. Now, you said subjective how you feel wins. OK, and it seems to be the case with almost everything. Like, like, how hard are you going? Do you feel like how what's your heart rate going up to? Or do you feel like your perceived exertions? Oh, your perceived exertion is going to win, right? Yeah. So Ben Levine was on the podcast and he was actually arguing that heart rate variability is extremely variable in terms of the way it's measured. And, you know, he just sees tons of variability, like plus or minus 25 percent constantly, depending on like the variety of factors, the time of day, their breathing, just everything like that. And he likes to look at resting heart rate, like first thing when you wake up in the morning, what's your resting heart rate as a good marker of recovery. And if your resting heart rate's higher than it should be, then it's kind of like, OK, maybe you're you're getting into this over non-functional overreaching, which I want to talk about overtraining. Yeah. But nice use, by the way. Thank you. That's good. But HRV. So do you think there's, you know, if there's some way people can kind of follow this consistent measurement protocol, same time of day, same posture, same control breathing or something that they do like a control breathing thing before they measure it, something that's giving them, you know, consistency. Yeah. The big ones in this particular area, these are all respiratory related. What you just described. There's lots of ways we measure readiness, performance, fatigue, like depending on which spectrum you're in here, people will call these different things. Load management. They're performance based ones. These ones you've all mentioned are in the respiratory physiology side. So that's great. We'll just stick right there. Now, HRV is one of them. Resting heart rate's another. More commonly, though, that we use our respiratory rate. And then you can look at something like CO2 tolerance. Let's just disregard those for now. We'll focus on respiratory rate. We'll focus on HRV and heart rate. Resting heart rate is a good sign if conditions are stable. If your resting heart rate becomes elevated at probably more than three to five beats per minute for more than a couple of days, that is a good sign something is happening. In this case, not a good thing. Right. So it's starting to become elevated, as you said earlier, generally indicates you're getting overcooked. Right. Too much training or allostatic load. Total stress. Not enough recovery or calories. Something's going on there. The issue with that is resting heart rate is incredibly unsensitive. It takes weeks for that to happen. You're well into that problem. And when you start seeing changes in resting heart rate, you are so far down that road that you've like we should have saw this weeks ago. Even first thing in the morning, resting heart rate, you're talking about 100 percent. Yeah. You will not see a change in first thing resting heart rate for a very long time into problems. The reason why people like HRV more is because it is far more stable. It is also like resting heart rate nonspecific. So you don't know what's happening, but that variability that you're mentioning that Ben talked about earlier, that's also the benefit. Once you establish somebody's standard deviation, what do they normally fluctuate, right? Some people are going to be really neurologically nervous system to be super stable. Some people nervous systems really unstable. That itself is a marker. How wide you range on your daily HRV is incredibly telling to what's going on in your system. Because of that, that sensitivity, I can see things happening really quickly. Now, some of the common mistakes with HRV are looking at the flat score, right? You know, if I said right now, like, what's your resting heart rate? And if I said your resting heart rate to 100 beats

even things like biofeedback training. We can develop more resilience within your nervous system, and you can objectively see that. And so we can use a whole bunch of different tools where we can give people. And we can say things like, okay, can you calm yourself down? Can you? Oh, yes, I can. Great. Well, then show me in your physiology. And you can see them looking at HRV data and going, oh, it's not moving. Oh, great. This is why we want you to go do A, B, and C. Or they can, like a bunch of different ways you can do it. So that's a lot of value in HRV, independent of just my single one ultimate recovery marker. In my opinion, respiratory rate is even better. When you see changes in respiratory rate, this will happen way before changes in resting heart rate. And this itself will influence both resting heart rate and HRV. If you start breathing more, something is happening. There's actually a really interesting paper. Laura Bloomfield did a couple of papers where she measured all these things: resting heart rate, sleep, HRV, and looked at stress. And one of the things she found in her second, actually two studies, and the second one found that you'll see something like your likelihood of experiencing moderate high stress. One beat per minute increase in resting heart rate gave like a 1% to 2% increase in risk. But a one breath per minute change in resting heart rate was a 20% to 30% increase in likelihood of experiencing moderate high stress. Which is a way of saying that stuff will flag way before resting heart rate. Resting heart rate didn't do anything, didn't tell them anything about it. But HRV and specifically respiratory rate shot way up. You can see acute stress. If I look at someone's data in the morning and your normal respiratory rate is say 12 breaths per minute overnight, and you're at 14, I'm like, whoa, something's going on. If you're at 14 for two days in a row, boom. You're going to get sick the next day, or you're already sick, or something like, hey, what's going on, Ronnie, you okay, what's going on? Like, no, my God, like something's happening. And so for me, when we're coaching people, like we're coaching them, I don't want to wait six weeks to start seeing problems happen. I need to go like, hey, this happened right now. What the heck is happening? What's going on? And from our opinion, HRV and respiratory rate will jump off the charts way before resting heart rate.

Rhonda Patrick: How accurate are respiratory rate devices that are measuring respiratory rate?

Andy Galpin: Depends on the device you're using. If you start going out to the wrist and the hand, we start losing accuracy, right? If you're actually using a chest strap, we're getting better. When we really care about it, like in our actually like sleep testing stuff, we're going to have a device directly on your chest. We're measuring not only respiratory rate, but we're measuring the amplitude of change in your chest. We're measuring the direct movement of it. Outside of that, though, respiratory rate's pretty easy to measure.

Rhonda Patrick: But I mean, if someone's doing this at home, are they going to be wearing a strap like while they're sleeping?

Andy Galpin: You can, or you can wear your wearable, your watch. But you said you lose accuracy if you wear your watch. For respiratory rate, it's okay. For HRV, we start to lose accuracy. But respiratory rate is actually pretty easy to pick up from a tracker, so you'd be okay there. HRV gets tricky.

Rhonda Patrick: And, and the respiratory rate. So you're mentioning the studies how stress would—it's very sensitive to stress, and that's not just like psychological stress. It's just exercise. It's any type of stress on the body.

Andy Galpin: Nutritional stress, environmental stress. Again, you'll see, if you remember a few years ago—well, a few years ago, we all remember COVID—there was a bunch of different devices that came out where NFL, the NBA, actually, I think they did it with Aura. They were able to have these like pre-COVID flags. And we had a bunch of professional athletes. And I'll give Aura some credit here. It was pretty good. What I'm saying is we would get an alert. We were like, boom. It's like somebody has COVID. We're like, what? No signs, no symptoms. And then days later, boom. Well, it's a combination: respiratory rate, body temperature, and a handful of other things. And they had this fancy algorithm. They just opened it up publicly last year. My friend, Dr. Ashley Mason's the one that—she was involved with all that studies. She was fantastic. Yeah. Like, I'll tell you, like, I didn't look at the data, I didn't read the papers, but for our athletes, it was pretty much spot on. We're like, damn. And you like have a day to prepare. You're like, okay, great, you're going to get COVID tomorrow. Like, we just knew it was happening. So those things can be pretty sensitive. Even again, that's a wearable on the finger, and they were able to get good enough with their data to figure out you're gonna get sick the next day. So it can be, yeah, stress. It can be nutrition. It can be actual like bacterial, viral infection, environmental exposure, allergens. Tons of things like that can flag that make people breathe more.

Rhonda Patrick: Now, would this change in respiratory rate indicate someone is transitioning from like functional overreaching to non-functional reaching? Maybe you can explain what that is.

Andy Galpin: Yeah. Okay, great. In order for you to create adaptation, we have to put in stress. That's how the body maneuvers itself. The more stress, the more adaptation. At some point though, too much stress overwhelms the system, and we start having negative adaptations. We start going backwards. We stop making progress. And eventually, actually, things get worse. You get hurt, you get injured, so on and so forth. At the end of that station, that is overtraining. True physiological overtraining is very rare. It tends to take weeks, if not months, to recover from. This is not—you're not overtrained if you're like, oh, I had to take Saturday off, I feel way better today. That's not overtrained. Overtraining is I couldn't exercise for two months, and then I finally started feeling better. So it's really uncommon. It does happen, uncommon. Before that, you get into what's called non-functional overreaching. So you're overreaching, you're pushing your body past where it should do, and you did it so much that when you actually recovered, you didn't get any positive adaptations. It was not functional. It didn't produce a benefit. So if you were to go this in the spectrum right now, if you and I had to go train, we got done, we would go lift, our acute performance would be worse because we're tired. Okay, great. But then we rest, and we come back tomorrow, next day, our performance is better. If we keep doing that, though, we keep training, and we don't give ourselves enough time to recover, we'll eventually go down in performance, down in performance. And then if we take some time to recover, we should have this super compensation. That would be a situation in which we overreached, but it was functional because it produced a benefit, produced performance enhancement, more mitochondria, more muscle—you know, fill in the blank for whatever you want. So we have functional overreaching. That's what we're after. It was functional. We have non-functional. You kept going. You either trained too much, you under-recovered, or both. Then you had to take weeks off, typically days off or weeks off, and you got back to baseline. Then overreaching is past that. That's what we're really getting at. We want to spend as much time in functional overreaching as we can. Then when we back off, we have, again, ideally a super compensation. We got the adaptation we're looking for.

If you really get into overtraining, it's hard to define because there's no marker of it. We actually have this really cool—Philip Larson and his lab in Karolinska Institute has published a bunch of really cool papers. There's a handful of very specific mitochondrial markers that they've identified. They can actually see overtraining happening before any other signal of them. There's like six or eight different metabolites they've got that they've published. It's really interesting stuff. I actually think they're onto something pretty smart there. Because of that, this is one of the exercise science problems. What are the signs of true overtraining? I don't know. You're tired, you're hungry, maybe you're sleeping more, maybe you're sleeping less, maybe you're not hungry. It's kind of like everything. There's no "this." It's just like, well, we saw people that were overtrained, and then some of them had less energy, some of them had more. It's all over the board. There's this classic literature on things like testosterone to cortisol ratio and cortisol DHEA ratios. There's lots of other little markers, but there's no one specific biomarker or performance marker or subjective marker or sleep marker that is like the definitive, yes, you're diagnosed with overtraining. That doesn't exist. It's a combination of all these things that we're looking at to try to determine whether or not somebody's in that spot or whether they're functionally overreached or non-functionally overreached. It's a pretty messy situation, to be totally honest with you. We don't exactly know what we're doing.

All that then underlying saying, all right, how does somebody know? I don't know. Take a day off. Do you feel better? Yeah, I feel way better. Okay, probably functionally overreached or non-functionally overreached. That's good. Good position to be in. Took a week off, still feel terrible. Okay, now we might need to deploy some more aggressive solutions because you may have actually pushed way past that limit. That is really the best way to think about overall overtraining.

Rhonda Patrick: What happens to someone's hormones, like testosterone, for example, when they're in non-functional overtraining?

Andy Galpin: Generally, what's going to happen along that entire cascade—in all that, you're going to be less anabolic.

Rhonda Patrick: Sorry, non-functional overreaching.

Andy Galpin: Yeah, yeah. I got you. You're going to start off and things get worse. Testosterone will go down. If you stay there, if you're not getting back into the functional overreaching—yeah. So let's just say we start. We're not working out, we haven't trained in a month, and then we pick it up again. You and I, we get after it, we're going. The first couple of weeks, we might see a reduction in basal testosterone. We've overloaded the system a little bit. Things might get worse, right? Your physical performance might get worse. Fatigue is setting in. This is a stressor. This is actually good. This is why you wouldn't want to come in and give yourself an anti-inflammatory. You wouldn't want to come in and give yourself—like, you're actually trying to induce adaptation here. And so when you see markers that look like they're bad, this is just a signal that says you're overloaded right now. Resting heart rate might go up. HRV goes down. That's okay. This is the off-season for our athletes. We expect these things to happen at the beginning of the off-season when we just start training again. Normal.

If you were to stop and you were to start recovering more, then you'll see testosterone come right back up and potentially almost likely not go back any higher, but it'll come right back up, and performance will go higher. So an acute—and I'm defining acute as like a couple of days or a couple of weeks of something like testosterone going down early in a training phase—it's very normal. It might stay the same, but it might come down a little bit. And if it does come down a little bit, I'm not stopping training. I'm not backing off unless we're seeing signs of extreme fatigue or pain or whatever. But that little bit of short-term, what looks like a negative thing, is not. It's a normal physiological response.

If we were to keep going, though, we didn't bring you out of that, and then we got into something like non-functional overreaching, then the testosterone is still going to be down or potentially lower. But then you'll start seeing the things of, now my performance has been down. It's been down for three weeks. It's been down for five weeks. It's not coming back up. Okay. Sleep issues, hunger issues, motivation issues. You continue to go, and you get into true overtraining. Now almost surely anabolic hormones are down. The few studies directly on actual overtraining suggested that something like a testosterone recovery might take a while. It can really struggle to come back. Typically, when somebody's like a little bit overreached, even if their testosterone is down, a couple of days off, it flies right back up. It's not really a compromised endological system there. It's just an acute fatigue.

Rhonda Patrick: What about in women?

Andy Galpin: Same thing. Obviously, testosterone total amount is lower, but same exact curve basically.

Rhonda Patrick: Okay. So most people probably aren't—I mean, there are athletes that might be consistently in non-functional overreaching, especially if they keep that vicious cycle of they're trying to train more to get better and they don't recover or they don't allow for enough recovery.

Andy Galpin: I'd say we've seen it more in non-athletes than athletes.

Rhonda Patrick: Oh, really?

Andy Galpin: Yeah, way more. Because an athlete's generally pretty in tuned, and they're like, ooh, I don't want to do this thing or whatever. You'll get feedback from them. It's oftentimes the hard-charging CEOs. This is the like, I'm burning the bridge, I'm on oftentimes a lot of stimulants or other things, I'm running a company, I'm doing this, I'm traveling a bunch. And then, oh yeah, all I do is high-intensity exercise training. And then because of that, I'm on a lot of stimulants, like I said. And then, oh yeah, then my sleep's not great, it's inconsistent, I'm in different time zones, I don't see my kid. It's that whole thing that goes—boom—allostatic load just gets through the roof, and there's no payback. That's the people we've seen more in the non-functional overreaching, and then they wonder why they're plateaued.

Rhonda Patrick: Yeah. They're not getting anywhere. I only—there's a few times where I get like, okay, I gotta just not work out today because I just wake up and I feel tired.

Andy Galpin: Yep.

Rhonda Patrick: How much do—when you're on training days, when you're working out hard, do you require more sleep?

Andy Galpin: Okay, I'm laughing here because that makes intuitive sense, right? And we have a number—we work with, I have a company, Absolute Rest, and we have the most famous—you would know the name—sleep scientists in the world, right? The most published ones. I've asked that question so many times. Nobody has a direct answer. It makes sense, right? I burn more calories today, I should sleep more. There's no compelling scientific evidence to suggest that caloric expenditure is directly tied to minutes of sleep needed. That said, like Jeffrey Germer has been doing this for 30 years, he's like, there is. He's saying, I'm telling you clinically, that happens. So I'm very much laughing when you say that because I'm like, man, I know what the science says on that, but my experience is different. And Jeff is like, no. The higher output sports need more sleep. High-volume people need more sleep. People that are like professional athletes, but they don't have a lot of caloric expenditure, don't seem to need as much sleep. I defer to Jeff on this one. I'm like, I think he's actually right. I think the same.

So it's a very funny question, but is that like true on a day-to-day basis? I don't think so. I don't think just because you train really hard today, you have to have more sleep tomorrow. I think on average over weeks, that might probably line up. But that's the best we can answer.

Rhonda Patrick: Because you know the opposite is true, right? If you're not getting enough sleep, then it's going to affect your performance, it's going to affect your adaptations. I mean everything, right?

Andy Galpin: There is nothing we can do to enhance performance more than sleep. There's no supplement, there's nothing that's even close.

Rhonda Patrick: Right. So sleep is like the best. I mean, and it's part of the recovery, right? Again, recovery is so important for performance.

Andy Galpin: When you asked about recovery earlier, that's our first step.

Rhonda Patrick: How does a person know if they are really getting enough sleep? Because as you mentioned, all these sleep trackers and this and that.

Andy Galpin: I'm clearly very biased here. This is what my company does at a very high level, right? So I have a vested interest in a different answer here than probably most. But we spent a lot of time—I've been fortunate to work with many of the highest paid athletes in the world, where we had unlimited funds to do anything. And we know at the same time sleep is so critically important. But the best thing we could do is send them to like a sleep clinic or a consumer wearable. And it was like killing me. I'm like, how is there not better sleep solutions than these? That's why we went and built Absolute Rest. How do we know if it's enough? We do it differently. We actually have a bunch of direct measures of follow-up cognitive and physical performance. So we determine high-quality sleep as a function of how are you actually performing. So that is a different answer for everybody. It can be a time domain. It can be—there's actually one of the markers we use is actually called Sleep Quality Index. It's FDA approved, tons of evidence behind it. That metric alone is an okay single number if you want to use it, but that has a lot of validation behind it. We start there, but like I said, sometimes it is a numbers game. It is the total amount of hours. Past that, it's way more interesting stuff than sleep staging. Sleep staging is not a good way at all to think about sleep quality. More interesting are things like fragmentation, sleep stability, sleep range. The amount of time you send in those arbitrary sleep stages varies wildly by cognitive demand. Your body is not asked to do the same things on every day, so it's not going to have the same sleep architecture every day. So the way that we define high-quality sleep—completely different. What we are working on right now actually is direct testing of next-day cognitive function. That's how we backfill sleep quality and sleep timing. And so we want to actually develop methodologies in which we'll actually test a whole bunch of different cognitive functions, and we can determine what is actually effective for you based on your actual functionality rather than an arbitrary set of numbers.

If that is like, what the hell is he talking about? Back all the way up and just say, how do you define good quality sleep for you? How is your daytime function? That is your thing. Are you fatigued? Are you sleepy throughout the day? Everyone's going to be somewhat sleepy, particularly in the afternoon, right? But is it detrimental to your performance? How are you performing cognitively? How are you performing physically? And then how much strain are you under? If you're happy with all those things, then I would say you have good sleep quality. We don't have to get any piece of technology past that. If you're failing or slightly suboptimal in one of those areas, then we might have to do some tinkering. We might have to do some follow-up. But if you're like, I wake up, I'm a little bit tired in the morning, but like, that's normal. Yeah, like I have a coffee and then I feel fine. A little bit tired in the afternoon, but I train, I feel good. You probably sleep pretty good. That's a pretty good marker. If it's not that, let's talk.

Rhonda Patrick: But other than that, you don't need to go out and get yourself tested. That's kind of how I feel. I feel like all those things, like how you feel. I used to do all the sleep tracking and Oura Ring. And I do have an eight sleep bed, which tracks my sleep as well. And the only time I use it, I mean, I use the cooling part and all that. But the only time I look at my data is if I'm like, I go out with friends and I'm like, I know I got like, you know, six hours sleep or something. I just—I'm just like curious, you know, I feel it like the next day, too. Yeah, yeah. Then, then it's like—that's when I use it. But, you know, it measures my resting heart rate, too. I'll look at that.

Andy Galpin: Sure.

Rhonda Patrick: It's not as probably as good as wearing the Oura Ring, but yeah.

Andy Galpin: I think that there's a lot of benefit in calibration, in awareness, and accountability. Right. So I actually don't even care which tracker you use or the accuracy, because for those three things, it's great. Here's examples. Some people have no idea how they're sleeping. It's like, oh, yeah, I sleep six hours and I sleep five hours a night. You look and you're like, you sleep eight hours a night. You have no idea what gets. So a tracker, accurate or not, it's good for accountability. When people know they're being watched, they make better decisions. Right. It's good for awareness. So pick your poison. I have multiple eight sleeps actually at my house. They're great. I love them. Awesome. Use that. Use whatever you want to do. If you're actually trying to get into the nitty gritty of sleep details, then like, you need to take an appropriate look at an appropriate set of technologies, not those ones. But if you don't care about that, there's tons of benefits from people just like getting somewhat aware and being held kind of accountable. People generally make better decisions, especially again, the folks that we work with where they know we're going to look, they know someone's going to be like, what did you do? And they're like, they have to answer that question. They just tend to make slightly better decisions.

Rhonda Patrick: What are some of the highest impact behaviors, like adjustments to improve overall sleep quality? I mean, I heard you talking about hydration in Y for hours and learned a lot. I talk about everything. Yeah, I learned a lot. But what I really—what I realized, you know, I like to drink hot tea, especially in the wintertime, like in the evening—herbal tea—and it is just detrimental to my sleep, because I'll have to wake up and pee once or twice; twice is like the worst. But I've been convinced that I have to, like, starve myself of water before I go to bed—like hours, like, you know, like in the three hours before bed, it's water fasting, like little, little bits of water. And then I can make it through the night without getting up once, and it's amazing. So I'd love to know—I mean, there's a lot of sleep hygiene, and of course you can talk about that, but, like, some of the high-impact behaviors, maybe things that people don't realize.

Andy Galpin: Yeah, you know, all the big stuff. I'll skip past it. OK, you got it all: cold, dark, you know, blah, blah, blah. Past that, hydration is one of them. My expectation is for people to wake up at most once per night. I would like to get you to zero. It's not always realistic. Past once per night—now we have something to fix for most people. If you're causing the damage by drinking too much water at night, then let's stop that. I drink tea pretty much right before bed at night. Generally, I'm OK with it—if it's not, then back it off. And if that means you have to go back to three hours, then that's what you gotta—have the tea at four o'clock in the afternoon, I guess. I don't know, have it back there, OK, no problem there. Other stuff that people generally don't think about—a couple things. Fatigue and falling asleep at night does not necessarily equate to downregulation. So we have something called the wind down index. We have a whole bunch of metrics we can look at. This is very common for the person who wakes up at two or three in the morning, and either that happens all the time, or when they wake up at two or three in the morning, they can't get back to sleep—really strongly tied to lack of wind down index. And so what does that mean? Just like with your kid, you probably have a 60- to 90-minute routine that that person goes through, and you don't even realize, but that is really critically important to getting you to land in the right spot. Your routine is probably 15 minutes—right, not yours, but you know what I mean. And so having a more appropriate game plan of what that is, it doesn't mean you have to avoid light, doesn't mean you have to avoid TV, doesn't mean you have to sleep with your phone in a different room. You can do all those things. You don't have to. We have tremendous, high-resilient sleepers that do all those things. But it is about a consistent routine, number one. Just try to do the same thing as often as you possibly can. We'll work out switching out behaviors a little bit later. That's another one. Ventilation in the room is critically important. People don't pay attention to this. One of the biggest reasons people wake up in the night is because they can't breathe through their nose. One of the biggest reasons you can't breathe through their nose is dander, pollen, allergens, something like that—start to block it up. Whether that's completely blocked or not, but then you open up and you start mouth breathing. Mouth breathing then means your tongue is a bigger issue, as well as your mouth can get dehydrated or get dry, rather, and you have a little bit of a dry mouth and you need to have a drink of water at night. These things can happen. This will wake people up a ton. You want to make sure that you have proper ventilation in your room. One of the things that also happens in this is CO2. CO2 levels rise above 900 parts per million. This will significantly and dramatically affect everything from sleep onset, sleep quality, next-day perceived fatigue, next-day arithmetic ability. CO2 getting too high in a room can happen because your doors and windows are all closed. If you have multiple bodies, you and your partner, your dog is in there—all of you are now kicking out CO2 into the room; you're exhaling. If that room is small and, again, lack of ventilation, that number starts to rise. If you are particularly sensitive to CO2 as well, which many people are, then that kicks off that entire cascade. You get pushed way more into sympathetic drive, and again, the biggest issue is you will see a subjective and objective massive change in fatigue and energy and cognitive function the next day. People rarely think and talk about CO2 concentrations in your room. This is a classic case of, like, I do all the things, I've listened to Matt Walker, I do all of it, and I still suck at sleep—you start thinking about what's going on in your physical environment.

Rhonda Patrick: OK, so a CO2 monitor. I have one. So getting a CO2 monitor—what's the number?

Andy Galpin: 900 parts per million. So you don't want to be above that. It would not be uncommon for us to just, by the time it's like seven o'clock at night, have 2,200 parts per million. Like, you're like, oh my gosh, it's up there. And it would take us hours to open up windows and just, like, let the CO2 clear in the house, right? You're talking about four humans, two dogs, and even in a pretty big place, that fills up pretty fast. So can you start that process earlier—as early in the day, can you open up windows in the house? If not, at least open up your sleeping space so that airflow can get in and out of that. If you need to turn a physical fan on to do that, that's another option, and it will drop pretty fast by doing that.

Rhonda Patrick: OK, what about people's nose that are closing up? I mean, you know, if you have a lot of pollen, let's say you have pet dander—I mean, do you have to get these allergen pillowcases? Like, how do you stop your nose from closing up?

Andy Galpin: OK, so a bunch of different things there as well. One: same exact answer—try to get as much of that cleared out of there as possible before the nighttime starts, right? Now you'll particularly see this with people who are like, my nose is fine throughout the day, and I just wake up at night—it only happens at night, only happens in my bedroom. Right, when you lay down or something—that's gravity, that's physically gravity, right? Like, you're standing up here, all right, and you go backwards, and then it's gonna sit there. So, like, part of it is that. So, number one, do all the things I just talked about, cleaning the air out of there. If you want to get an air filter and then specifically put it in or above or around your bedroom, that is a great option. So you can go there as a next step. Third step is you can just use Flonase. You can use a very simple nasal dilator, right? So whether this is actually, like, a nose strip that you can put on—we use a bunch of different companies for this—or an actual, like, injection, right, like again, like a Flonase, and you can squirt it in your nose before bed, dilate your nose—you can stop having problems that way. So those are three or four different things you can try. We've used and will use all those things pretty consistently, and they're all pretty beneficial, and they work pretty well. There's some amount of just, like, morning gunk you'll have. That's normal, that's OK. But if this is consistently waking up with dry mouth and nose completely clogged, then I would do all those steps. Past that, then you've got to really start thinking about special pillowcases and different solutions like that, but those are more expensive. The rest of the stuff I mentioned is cheaper.

Rhonda Patrick: So if you were gonna, let's say, have the three highest impact behavior changes to improve sleep.

Andy Galpin: Yeah, I'd say, like, have a consistent approach—timing, system, whatever you want. Routine, number one. And I want to be really clear—I know I'm running out—but that doesn't mean, like, 45 minutes of breath work and meditation. Like, that's not the routine. The routine can just simply be, I do the dishes, and then I brush my teeth, and then I check my—like, that is fine for the routine. It doesn't have to be this big, like, 90-minute, my phone's gone, and, like—that's not what I'm referring to. Just do the same thing as much as you can in the same order and the same routine. Number two, make sure that your physical environment—past temperature, past sound, past light—like, you're taking caution of that. If you don't have a CO2 sensor or an environmental scanner—we send that out to everybody, so they always have those—just open up the ventilation anyways. So you can do those steps regardless of the testing. So that'd be my second biggest one. Another one that I would maybe say pop off that's abnormal—yeah. Honestly, like, the wind-down index is pretty popular. So making sure just because you're fatigued and you know you're going to fall asleep quickly, that you're still doing something to make sure that your parasympathetic system is actually turned on—that's a little bit different, right? So we always say, like, turn on the off switch that we want to do. So whatever that takes for you to do it—some people, that's reading; other people, that's not. Like, for me, reading doesn't do it for me, breath work will not do it for me. I actually have to have something that physically triggers my brain of, like, gives me permission to let go for the day. That means I'm doing something that is so unproductive—I'm probably, like, reading some blog that four other people read about what the Seattle Seahawks did with their 12-string wide receiver—like, something that is, like, clearly not work-related for me, that is what I feel like is a waste of time. That is just a trigger for me to go, yeah, it's your time. You don't have to be productive. You don't have to answer anybody—all the input, everybody wants something from you all day—your space. So I'm doing that, I'm watching something non-inspiring or motivational on TV, whatever the case is, right? Like, that's hunting videos for me, that's, like, outdoor stuff. I'm, like, watching cool things like that—it makes me super happy and I check out. That doesn't work for Natasha—like, doesn't work for her at all. Whatever it is that cues you that your day's over, you give your brain permission to be done for the day—that's it. So that would be my three big areas that people can try.

Rhonda Patrick: I love it. It's funny, I do those things, and I didn't realize that the routine—it really is. When I break my routine, I have a hard time falling asleep. And my routine is, like, a simple thing, you know, where it's like, you know, I brush my teeth, I wash my face, and then I read the—completely non-work-related thing as well. It's gotta be, like—I never get on Instagram. I don't get on social media. Like, I can't—it's too work. It's work for me, right? So yeah, it's gotta be, like, completely separate from work. And relaxing music.

Andy Galpin: So it depends. Like books or—

Rhonda Patrick: No, no. So I do, like—I haven't been reading books at night in a while now. I read them during the day, just because the light component. But no, I'll just read, like, news stuff, or—

Andy Galpin: On your phone.

Rhonda Patrick: On my phone, yeah. Yeah, that's cool. It oftentimes will be—I will read, like, some cool science stuff, but it's not necessarily, like, health, so I don't feel like it's, you know, my work. Technology or whatever other fun stuff. Relaxing music—we play—I like to hear some relaxing music; that also helps. But no, this has been super awesome, Andy. I really appreciate you coming out. And let's talk about—you've got this podcast, Perform. You talk all about—I mean, it's you and also other guests you have on that are experts.

Andy Galpin: Yeah, it's seasonal. So we did 10 episodes the first season, and then we took, I don't know, five or six months off, and then season two is out now. No guests season one, just me going nuts. And then we brought in some guests this season, and we're actually gonna finish up filming tomorrow. We'll be done for the season. We'll take a little break, and then another set will come out later in the fall. So I can't do the—I don't know how you all do it, like, the consistent podcast. It's a—poof—it takes my soul, in a good way. Yeah, super fun. Appreciate you bringing that up. It's, like, Perform is the name of the game—like, we want to help people perform at their best, whatever that means to them, like, however that means to them. So yeah, enjoy it, love it. Yeah, thanks for bringing it up.

Rhonda Patrick: Yeah, you've got a couple other things you mentioned throughout the podcast, too.

Andy Galpin: Yeah, obviously, we're building that human performance center in Dallas, which is really awesome. I can't wait to share with people some of the technology that we built inside that thing—it doesn't exist anywhere else in the world, it's, like, super exciting. The ability for us to conduct research out of there, to do studies that I've wanted to do for decades—you know, it's like, well, that's just not feasible anymore. The team down there at Parker has removed those barriers. They're like, make it world-class, and we're making it world-class. We're doing a study right now—actually, we're actively recruiting for it—maybe I can pitch that if that's cool with you. My grad student, Zoe—she came with me from California—and Federica, they're running a study where we're looking at sleep across the menstrual cycle. Stunning enough, there's not a lot of research on this, and the stuff that's been done is questionnaires and maybe, like, a PSG—like two days here, two days there, two days at the end of the cycle or something. So there's still a bunch of unresolved questions about what actually happens to sleep quality throughout the menstrual cycle. And so we're actively recruiting. So if you are female and you are interested in this, I would, like, love to have you involved in our study. You can be anywhere—you don't have to be in Dallas. So it's open, we're recruiting, we're doing an open protocol. You get a bunch of stuff with it, but we're gonna run full clinical-grade, FDA-approved sleep analysis every night throughout the entire cycle. So we'll do cycle mapping, we'll do blood, we'll do urine, we do a bunch of cognitive stuff. And so we're really gonna see, like, is sleep changing in people with a normal menstrual cycle across the window.

Rhonda Patrick: What age range?

Andy Galpin: 18 to 35. So younger, healthier, you know, all that stuff. We really wanted to do it—actually, Matt was trying to get us to do us in menopause stuff, and I was like, I want to, but I got to answer one question, like, at a time rather than two at a time. So it's just cool stuff like that, that we can do because of some of the technology we have. But yeah, we're actively recruiting—that's our first, like, big study out of there. And then we got a bunch of other ones. But yeah, the performance center should be open next year, hopefully. That's exciting, and people can come down, check it out. It'll be open to the public too.

Rhonda Patrick: Yeah, I'm heading to Dallas in April. I'm sure I'll be back again. But yeah, I'll drop you a line when I head back there.

Andy Galpin: Yeah, let us know—super excited about that. Yeah, and grad students too, if you want to come to grad school. We have an online program—so we can get a master's in strength and performance with me, that's fully virtual, or you can come in person and then work in our lab. We have a lot of projects, so welcome all the bodies. So bring it. Every time I say that, people are like, oh my God, your inbox—I'm like, I don't care, bring them all.

Rhonda Patrick: That's awesome. That's awesome. Well, next time, I'd love to—we talked a lot about nutrition and supplements and recovery. I'd love to get into strength training and protocols and resistance training, strength training, hypertrophy training.

Andy Galpin: Yeah, you know, I got to tell you something before you leave and get out of here: I'm so proud of you. The fact that you post those strength training videos—and I know what happens in the comment section to that—like, it's everything for me not to just be, like, hammering everybody on there. But it is really hard for people to post stuff like that when you know what's going to happen, but you're very courageous in putting that stuff up there. I think that helps a lot of women. I think it's dope as fuck. I think it's the coolest thing.

Rhonda Patrick: Thank you. Yeah. No, I mean, I'm, you know, starting out, and I think it's great and want to encourage other women too.

Andy Galpin: Yeah, love it.

Rhonda Patrick: Awesome. Thank you so much, Andy. Been a real pleasure having you on.

Andy Galpin: Appreciate it. Can't wait to chat again, and it's been so long coming.

Rhonda Patrick: All right. That was amazing.