180. The Truth About Cortisol, Insulin & Overtraining | Shawn Arent, PhD, CSCS

Welcome to Medicine Redefined, a podcast focusing on helping you reclaim ownership of your health. I'm Dr. Darsha, and I'm Dr. Ultima Shraja, where your hosts, hair to challenge conventional practices and uncover the stories behind pioneers shaping the future of medicine. Our conversations not only focus on the individual level to dissect common practices for health optimization, but also zoom out to enhance systemic change. Join us as we look to break the status quo, move the needle forward, and put the help back in healthcare. Social media is flooded with hormone optimization advice that can actually sabotage your performance. Arches today is uniquely qualified to separate fact from fiction. He's also repeat guest that long-time listeners will recognize, and he is none other than Dr. Sean Arnt. Dr. Arnt is a leader in the world of human performance and sports science. He's a professor and the chair of the Department of Exercise Science in the Arnold School of Public Health at the University of South Carolina. He also directs the USC Sports Science Lab. Previously, he was professor and Rutgers University, where he directed the Center for Health and Human Performance, and this is where we cross paths, and he has been a mentor to me since. Dr. Arnt's research focuses on the relationship between training, nutrition, and stress, and their implications for health performance recovery. He is a certified student and specialist with distinction with the NSCA and a past president of the International Society of Sports and Nutrition. His work has been recognized with numerous honors, including the NSCA's 2017 outstanding sports scientists of the year and the Lifetime Service Recognition by the US Army. He has received grant funding from the DOD, NIH, and the Robert Wood Johnson Foundation, and has worked with the US Special Operations Command as well as teams and athletes in the NHL, MLB, NBA, and NFL. I brought Sean on to cut through the noise and around hormone optimization, a topic where misinformation runs rampant. About halfway through our conversation, I realized there's no way to cover this comprehensively in one episode. So we decided to make this part one of two. Here we'll discuss cortisol and its misconceptions and performance. Sean clarifies the central role of cortisol in mobilizing resources during exercise and explains why acute elevation differs fundamentally from chronic stress responses. We then switched to the other villain that people often talk about, and that's insulin. So insulin regulation is very critical for metabolic health. And we talk about the importance of insulin sensitivity over absolute levels, even touch on CGMs and exercises profound impact on glucose regulation. From there, we talk about growth hormone physiology, specifically the scientific perspective on GH's role in recovery, metabolism, and tissue repair, and the evidence-based insights into training and use hormone responses. I was also curious what Sean's comprehensive endocrine assessment protocols look like, and his systematic approach to biomarker analysis in high performance individuals, including optimal testing frequencies and clinically relevant markers. We leave it at sex hormone optimization across genders, primarily talking about males, he shares his professional insights into testosterone, and estrogen functions in both men and women, plus the impact of stress, nutrition, and training load on hormonal balance. Now with that for the delay, please welcome Dr. Sean Art. Dr. Sean Art. Welcome back, man. Hey, thanks for having me back. It's always good to see you. Yes, yeah, always good to get the tech issues out of the way. I was looking back at the archives, man. You were episode four nearly miles, not early, man, I was like, what are you guys up to now? I think we just published one 70 or 171. Holy crap. Yeah, okay. Now I'm feeling really old. Now, man, last conversation was highly entertaining, highly educational. So I do recommend that the listeners go check that out. We touched on a variety of topics when it comes to performance. And here, let me just set the stage a little bit for the audience and why I wanted to get you back on. I think as you're cruising through social media, I was maybe a couple months back and you come across content. And I remember coming across a clip where an individual was talking about the acute effects of growth hormone from certain training style and was giving general recommendations on how this is the optimal way to train. And we've talked about how there's never one optimal way, right? And this one was shared and reshared and actually sent to me by multiple people and I was like, okay, this is something that really we should spend some energy talking about, particularly with the advent of GLP1 agonist and how much attention people are paying to hormones. You have TRT clinics that are popping up every block down the street. And I think people are really attuned to this and are sort of appreciated. I couldn't think of no better person who can come on here and educate myself and our listeners. And just for context, we'll keep this conversation centered around performance. I think if we start diving into disorders and whatnot, we'll be here forever. With that said, I thought we'd start by talking about the one that most people villainize the most and that would be cortisol. There you go. And Sean, if I may, I'll even say this to you that after I graduated in undergrad, I spent a couple of years working as a good assistant coach and even in that time in 2011 in the fitness industry, there was this notion that you got to keep your workout to 60 minutes, including the warmup because you don't want that prolonged cortisol response. It's going to completely negate any gains that you might have accumulated. And so I myself was a victim of this mentality. With that said, what do we need to know a high level about cortisol and we can go from there? So I think first of all, okay, let's say what is cortisol? It's a stress hormone, right? It above and beyond anything else, it's a stress hormone and it really plays a critical role in fuel mobilization, right? And that's why the stress part of it is a good thing in a kid mobilized resources when you need them. That's the whole idea. And so it fits well with the cataclysmines with fight or flight. But I think what's really important with understanding cortisol is there is a very tit. This hormone is very different in terms of how we interpret its presence. They're talking about an acute or a chronic effect, right? So acutely, if you're doing high intensity work, right? So you're doing a hard resistance training session doing hell, even if you're running for long periods of time, cortisol is going to be an important modulator in all this acutely cortisol mobilizes resources. If we block cortisol with dexamethasone during exercise, your performance goes in the toilet, right? Because you cannot mobilize resources and it's funny because we've done a lot of work looking at the central role of a cortisol threshold. So where's this stress threshold with different intensities of exercise and when does it become more and more important? And we'll typically see cataclysmines show up first. Cortisol being a steroid hormone tends to come a little bit later. So we'd see ACTH or adrenal corticotropic hormone show up more during the workout cortisol kind of during the recovery into that period of time. But I think what's often misunderstood about it is somehow the notion that cortisol is bad. And chronically, this could be very true. We'll talk about that in a second has translated itself into the acute part of it with exercise. And so all of a sudden we see these cortisol blockers and manage cortisol and decrease cortisol. It depends on the context because in certain contexts, if you decrease cortisol, that's not a good thing. And even during the recovery phase, cortisol is still playing an important role in the remodeling and the recovery that's going on. One of the things that you want to do is just be able to recover from it a bit more quickly. And we've done some work with different supplements and things like that. And I think that the reality for us is we worked. One of the companies like, oh, it didn't stop cortisol. You don't want it to. That's a good thing. You don't want to stop cortisol, but you recovered from it twice as quickly. That was great. Now, chronically, this is a different story. If cortisol is chronically elevated because you were constantly in a high engaged sort of high stress state, cortisol is a catabolic hormone when all of a sudden done, right? It is a catabolic steroids, as opposed to your animal steroids where there's growth involved. With cortisol, its job is to break down. So if we have chronically high levels of cortisol, the entire system can fairly readily fall into a bit of a state of dysfunction, right? Because we're not recovering. We're constantly in the state of breakdown. So we want cortisol to follow its normal patterns where it tends to be at its highest as you're starting to wake up, right? Actually proceeding waking up cortisol starts to rise to get the body ready to wake up and be engaged for the day. We tend to see it stabilize through about the middle portion of the day, and then it will start to climb or it should at night, right? And so one of the things we often see is depending on lifestyle factors, depending on maybe how late in the day you worked out with high intensity, we may push that cortisol curve a little bit and not recover from it quite as readily. It's also the problem with short sleep because sleep plays an important role wherein that is a time where the system is recovering. So if we start waking up too early on short sleep, cortisol has already started to rise, right? It's doing its job. This is a natural, diurnal pattern, right, follows our natural chronobiology in that case. And so with that in mind, really having an understanding of cortisol, good cortisol bad, it's not that simple, right? Because it depends on the scenario we're talking about. But certainly with exercise and especially high intensity type work, you want cortisol. Cortisol is not the bad guy in this. Cortisol is an absolute necessity for those high intensity engagements. Bronically, we want to be able to recover from it. So we want ebbs and flows in terms of when cortisol spikes, when cortisol is at its highest from a secretion standpoint, and then to be able to recover from that. So I think understanding that background to it, and I think unfortunately in an effort to make money or villainize or demonize certain things because now I can give you the solution for it. I think cortisol kind of fell into that and the media really latched on to it, the social media. Cortisol in and of itself is neither good nor bad. It's a necessity, right? It plays a fundamental functional role for us. If it's chronically elevated, we don't want that. If we block acute elevation, we can have real problems, right? So it falls in the function part. And it's interesting because even dysfunctional cortisol and really your HP access to your hypothelamic, pituitary adrenal access. cortisol is part of the end product of that entire access and that access is really a hallmark of stress management, stress response. And when we look at that from that standpoint, really that dysregulation of that access is a hallmark of stress related disorders, like depression, like anxiety, even like PTSD. And so it's not so much that because cortisol is high or low, it's that it's an inappropriate response. It's an irregular response to how we want the body to typically handle this stressor. And so we see that with re-regulation of that access and a normal cortisol response to a stressor, we often see a bit more of a re-regulation of the mental health side of it too. So it's a pretty cool tie-in here in terms of what we see across that spectrum with stress and stress related disorders. How often do you see a low response to an acute stressor, maybe in an athlete or somebody where you're like, oh, you're actually not responding the way you should? Yeah, we'll often see that with overtraining, right? And so what'll often happen is, and what it comes down to is in the early phases of overreaching and maybe early stages of overtraining, it's not a common see very elevated cortisol response, especially if you're measuring chronically. But what gets really interesting is as they get into this state of sort of dysfunction where it's non-functional overreaching or we try to get in to overtraining, we may see baseline cortisol high because you never recover from it. But your ability to elevate it acutely is blunted because of the ACTH response or the arginine vasopressin response. That's the other thing is, so ACTH is, yes, the upstream regulator of cortisol in that whole access. But with exercise, actually, arginine vasopressin is a more potent stimulator of cortisol than ACTH's in many cases. So they go hand in hand when we look in it from a stress response standpoint. So my point in that is, in these phases where, and it's funny because people would like to term that adrenal fatigue, we got to stop using that, man, it's not even a real thing, right? The adrenal fatigue is not a thing, but it's not that your adrenal is worn out. It's that you can't mobilize your resources, your system is worn out, but your system is shot. And so basically, if cortisol doesn't rise in that state or rise sufficiently, you can mobilize resources. That's another way of your body basically putting brakes on everything, right? You can't do this now. And so we will see it in some cases there. I would say that we don't tend to see that a lot. And the reason I see that is, at least it from a research standpoint, I would argue that in the SWAT science, human performance world, we still have not actually done a true overtraining study. They are very difficult to do. However, we can take lessons from studies that have been done in the military with Army Ranger training, some of the work that Friedle and Nindal and others have done, where they show these hormone responses under these extreme stressors that we simply can't replicate in the lab. And so I think we've looked at overreaching a lot more than we've looked at over-training. That being said, there's still been important lessons for how resources get mobilized or not. And at what point we just start to see these chronically elevated or suppressed situations. In this case, with cortisol, it's usually that chronic elevation, but an inability to respond acutely in the way that you would think in order to be able to do that level work. So you mentioned highly engaged, high stress individuals. I know a lot of people that massed that descriptor, especially the guy in the mirror, and I look at it. Yeah. Actually, maybe before I ask that question, I'm also curious how often you'll see, as you mentioned, the highest response will be proceeding wake up in the morning, right? Yep. Over time, wake up is for you. Do you find that on an absolute metric, that is higher than any type of exercise response on, but I shouldn't say any type of the average individual, myself, if I have a heart-training session, can I even get it to a level that would be higher than my early morning levels? And as a matter of fact, at the very least, you can get it on par with that. And the reason I say that too is we had done some work actually when I was at Rutgers, and we were looking at overweight, no-beasts, individuals, and real post-prangial metabolism. That's the background of this. But we were comparing resistance training to aerobic exercise in order to help with that effect on lipid resolution and mobilization or metabolism. And what we actually saw was that those in the resistance training group, actually, it was funny. The cortisol peak in the morning was prolonged because exercise kept it up there for a little bit longer. Now, people might look at that as a bad thing, but you're like, no, it's just a whole mark of when they were doing this. And it was funny because normally, if we were to do that work later in the day, like mid-day, right? Sometimes, if we're specifically looking at, and I've done this for decades with the work that we've done, if we want to actually see the effect of the cortisol response, we will usually try to run people between about 10 a.m. and 3 p.m. because it's when that level tends to be most stable. The reason that becomes useful then is any fluctuation we tend to see in cortisol becomes more of a function of the response to that stressor rather than influences of the normal diurnal variation of highs and lows. So it's a bit more stable. We have to control for meals because of that because meal timing can influence this as well. But that's fine. That's not that hard to do. But certainly, at certain times of the day, you can jack cortisol up. You can get it to these pre-waking, early waking levels. Question is how fast do you recover from it? And there's certain training modalities or certain stressors that may do it more than others. But cortisol has a tremendous ability to rise acutely and then recover if you give it the opportunity to do so. Yeah. That was Patrick's study, right? Are you talking about? Yeah. Exactly. Yeah. Yeah. Yeah. Yeah. I remember that. I wasn't mad with you at that time. That's right. So coming back to this chronic response, elevator response, which a lot of people experience, I think the world is chaotic to say the least. Nowadays, and you highlight a social media, it had a lot of good, but certainly a lot of bad there too. And it can elevate the stress responses. People tend to stay up late at night. You're sleeping less and less, kids spending time earlier on in those really developmental years. And suffice it to say, people could use some strategies to manage some of these, I don't want to say cortisol. I'll say stress. So with that said, what do you think the lowest hanging fruit that people should be thinking about when, maybe before you went, I say that, what would be a good way to assess or some signs that might be like, okay, maybe something is going on and this needs to be looked at. Or rather than just, I'm a high stress person, I'm in a high stress job, are there subtle things that people could think about that might suggest that this needs to be addressed in the first place? That's a good question. So I think there's a few things. Paying attention to feelings of chronic fatigue, so not chronic fatigue syndrome would say, but just always being tired, right, from that standpoint, or this feeling of being overwhelmed or anxiousness that kind of go along with these things too, and how is that sitting with you to do this? But I think the other thing too is from a simple metric to track as well. Are you seeing changes in your resting heart rate, especially upon waking? Is it starting to trend up? If you are wearing a wearable, what are we seeing happen with HRV over time? And so they hadn't. HRV would be a whole another topic that we don't want to get into today, but to put in simply much like cortisol, it is oversimplified. But I think that the reality is when you start seeing these indicators that you are a little off or you're starting to realize that you, for lack of a better way, you feel stressed, right? And I would say probably the better words you feel distressed, right? Because stress is another thing cortisol, where stress gets a bad rap. Without stress, we die. The stress challenges the organism, forces us to grow, and forces to develop and adapt. So it's not that stress is bad. It's the distress, the negative influences, especially the things that aren't under our control. Need a little bit of that learned helplessness that goes with that and things like that. But I think when you start to look at the nature of the stressor, and really sometimes the compounding of stressors, this was a really useful lesson we learned working with athletes. Again, when we were at Rutgers and we were working with the women soccer team, I think we got pretty good at controlling training load. We're pretty good at controlling the training itself, the lifting, even some of the nutritional stuff. I started to realize, man, we're still missing big pieces of this puzzle from a human performance standpoint because we're counting for two hours of the day. What's going on in the other 22? And this is when we're working with quest diagnostics and their blueprint for athletes. And we started to be able to do these biomarker panels. And really, in some cases, looking at the inflammatory and the stress responses and stress hormones and realizing that besides just playing soccer, you've got classes and you've got relationships and you've got environmental factors, you've got team dynamics. There's all the travel, right? And all of a sudden we started to capture the other 22 hours of the day and funny enough that year we started a counterfeit. That was the first year the team made the final four, right? And it was one of those where we're able to start to consolidate their sense. But we started to pay attention to those little things. How were the players feeling? How were they performing? Right. So that's the other thing too is, you know, if you're exercising and you start to notice that your efforts in the weight room, your efforts running, cycling, whatever your jam is, also an interest to feel a lot harder. If you see your performance declining, might be time to take a look at what's going on around you from the standpoint of is your system not able to adapt and repair in a way that facilitates this continued improvement or at least a maintenance of performance? So paying attention to those little things when they feel off, I think is important. There are certainly some days where you might just get trained through the suck, right? There's just some days you're not feeling as much as those. We don't want to take all those days off. But I do think it's important to listen to your body and know when you might need some extra rest, especially if you're operating on short sleep chronically. There's going to come a time where you're going to have to make up for that. Right? Otherwise the system's in a state of disrepair. And not that all of it is because of cortisol, but continued elevation, that is not going to be helping you either. Yeah. And to come back to your point about monitoring your some of those HRV resting heart rate. And I know a lot of people wear an Apple watch or a ring. Now people have eight sleep as well, which you'll check those metrics. I think something to mention to people about that is you want to look at trends, right? So if you are not needed a trend, and if you're, especially if you're going under the weather, you have a cold, not a good time to be looking at your elevated heart rate couple of BPMs and say, hey, that's contributing to that. Something else that actually comes to mind, I think one thing we know is different hormones will influence our body composition in various ways. We're going to touch into that. We also know that like, for instance, I'm getting ahead of myself here, women because of their hormonal profile will tend to put adipose in different parts of their body. Sure. I remember at some point learning that one sign, you mentioned it's a catabolic hormone. So if you're not able to put on any muscle mass, if that's a goal. And as you mentioned, that you're not able to do that, despite being fatigued and you're like, hey, my sleep is relatively dialed in, I think my nutrition is somewhat on point. I'm training hard. I am not able to get any muscle and presuming any of the other hormones are still normal. One thing that I remember people talking about is that if you tend to put a lot of adipose tissue around your belly, particularly for males, that might be a sign of elevated cortisol as well. Is that, is there any truth that? Yes and no. I don't want to dismiss it entirely because it's funny. There's a fairly high respect to scientists. One in particular, I can think of that they like to say that cortisol has nothing to do with making you fat. Cortisol is a catabolic hormone. How could you possibly store fat? One of the things that we see is, even though cortisol doesn't always directly result in this body fat accumulation, it is a catabolic hormone, I get that. But there is some pretty strong evidence for cortisol's role in adipocytes being more sensitive to being able to store fat. It also plays a role in cholesterol synthesis and cholesterol in cortisol in terms of how they interact. There can also be some de novo lipogenesis that occurs with that, so making new lipids for storage. Yes, chronically high levels of cortisol, though it is a catabolic hormone. There is some pretty compelling evidence for the role that it can play in increasing fat storage capability and some of that may be somewhat through the loss of muscle and things like that. And again, separating out acute versus chronic effects is very important there. So with that chronic elevation, there's a sensitivity with some of the beta receptors that occurs that that seems to favor some of that fat storage. Certainly because of where some of those receptors might be located, that more central adiposity would not be uncommon. Now, we will say this, though, it gets a little bit compounded and I think people have to be very realistic with themselves because there are some situations where in this sort of high stress, and not just psychological stress, but other high stress or situations where cortisol may stay elevated. What other lifestyle or behavioral factors may be playing into that fat deposition because it could be that you eat in response to that. And cortisol itself can also change certain cravings for different people, right? In terms of what they're craving to handle that because of this, that the chemical signals to the brain. It's probably not a, it's not a super simple relationship where cortisol makes you fat. It's more like cortisol is indicative of a situation that can lend itself to story body fat. And cortisol itself can also play a role in this, right? So it's a mediator as well as a direct causal factor, and you layer those onto each other. Now, the only caveat is, what do you think about how long it takes to put on weight in something, especially store fat? If you wait until you put on enough fat that you notice cortisol might have been elevated for quite a while in terms of some of that. So I don't know that I would use that as my benchmark in terms of my first one, but for a lot of people that may be the first time that it makes them sit up and take notice. They're like, what is going on? I can't lose weight. We'd stable what I feel like I'm getting fatter or something like that. Yeah. All of those things may be triggers to look at everything else that's going on. And it may be that cortisol is a symptom of what the whole process has been in order to get you to. You mentioned beta receptors. Are they located in every organ or certain? Yeah. So certain, and certainly depending on whether talking beta one, beta two, beta three receptors in the role they play in like policies and things like that in terms of, and again, the colamines will play a pretty big role there as well. We see it at the muscular level, at the adipocyte level and things like that. So even the receptors themselves that are responsive to the stressed pathways and the chemical signals that go with that can also play a role here too in terms of whether we're talking like policies or lipogenesis, how that fits together. Those are interplaying pathways that make a difference there. We highlighted that sleep is very important and we've talked about sleep multiple times. So I'm not going to get a dive too deep into that. You did mention earlier with that obesity study that we were working on together that we had to control for nutrition. Yeah. Sandler a bit more about that. How does your nutrition either blunt or elevate that response if at all? It probably has more to do with where it's going to tie in for the entire system recovery. So it's not necessarily that one food source will magically raise or lower cortisol. It's going to be the overall effect on the system in terms of fuel mobilization, but also where the storage is occurring with poor nutrition. And we're looking at a situation where we're not optimizing muscle protein synthesis. We may favor denobolipogenesis. We may be looking at things that do not lend themselves to an otherwise ideal body composition outcome or performance out in that case diets can have an influence because diet does play a role in your exercise performance. Having the right food sources here's the thing is there's been a couple studies now. And I think people forget this at times, but even the role that the mapper nutrient make up, if somebody's not say a ketogenic diet in order to allow for those fats to become glycogen in order to be able to be used for other intensities, the entire hormonal system is going to play a role, including insulin, glucagon, cortisol, piata. They all play a role in influencing that response. And if you're not adequately recovering and it's for example, there's some cool studies where they've actually shown that with carbohydrate refeeding, after intense exercise, you can actually help reduce the cort the cataclysmine response to facilitate recovery faster. And cataclysmines and cortisol will also feed off each other, if you will, in terms of the things that typically influence their secretion and their overall response. So again, that dietary influence is important in making sure you're providing the raw materials so the cortisol doesn't have to continue to break down your body's resources in order to provide it otherwise, right? Because in the absence of feeding with protein and things like that, the body will find a way so it'll break down muscle tissue in order to provide amino acids. That's something that cortisol is very good at. So if you're looking at cortisol's role in that, again, it's mobilizing fuel, it's mobilizing resources. Yeah. We've mentioned cataclysmines a couple of times. So just for those listening, so we're talking about norepinephrine, epinephrine, dopamine right? Anything else? Okay. Cool. You're going to look at the exercise response, epi-inorepi, or you're two primary drivers, but certainly dopamine plays an important role here within other factors that facilitates that too. But yes, and for those that might be listening in Europe, we're talking to adrenaline and norepinephrine. Yeah. It's the same. It depends on where you're from, but same idea. Yeah. So two part question for you. When you're working with high performance individuals, not just athletes, but cognitive performance, I'm putting it all in the same bucket. And what's your assessment process, like what labs are you looking at, again, from an optimization standpoint? And then two, all the levers that we can pull out, right? Stress management, sleep, nutrition, exercise. Where do you like to start if you do find that is not in that optimal window? So there's a couple of things here. One, I almost never like to look at those biomarkers in isolation with that also knowing training load or other stressors that are going into this. And the reason is you may see these values come back. And the next question, now what do I do about this? If you don't know what's been going on, you have no idea where to start with modification. All you know is these values look off. And the other thing too is I rarely, if ever, will rely on a single time point in this case. What's so important for me when working with these really high level performers is change over time, right? Because there's such individual variability there. So having more than one data point becomes really useful for tracking how they're responding because that way if we modify their training, their diet, their sleep, any of those sort of major drivers, I need to know that they're working. Like how is it working? What's it doing? And typically when we start looking at blood panels, part of it's going to depend on what the question is, we're asking one thing that I've learned to appreciate these panels more and more for is the role in the nutrition piece, right? And that may be the one place where you can do a single snapshot, get a good idea for where somebody's status is when you look at iron, ferritin, when you look at omega-3s, omega-36 index, when you start looking at magnesium, when you start looking at those different actors that you can get at with some of the important vitamin and mineral relationships, the iron storage and things like that that go into it, especially for a lot of our female athletes. That becomes really useful. But again, looking at that over time and if we're going to do a dietary intervention, we want to know that it's moving the needle. How is this actually modifying what we think needs to be modified? But other than that, typically, unless I'm working with a pro team or athlete where the collective bargaining agreement stops me from looking at these things, I'll typically include cortisol, both free and total, testosterone, free and total, growth hormone, IGF1, a few inflammatory markers, especially IL-6. We've been using CRP a bit more recently in terms of, we tend to find it to be a fairly reliable marker over time in terms of what we're looking at, TNF alpha, if I need to, IL-6 and CRP usually give me a pretty good snapshot for most of what we're doing with that. Certainly, if you're looking at your comprehensive metabolic panel and your CBCs to be able to get at some of the immune markers, but then also looking at hemoglobin and hematocrit, looking again at iron, and some of the things that may be indicative of recovery. I don't typically caught up too much in some of the liver enzyme markers unless there's something else going on because exercise will heavily influence the stem. So in almost every athlete, we typically see AST and ALT elevated, and we don't freak out about it because their last workout probably influenced that. But again, we track these things over time. We've done growth hormone, we've definitely found to be more responsive in females as a marker of what's typically going on. We'll typically look at estradiol and progesterone depending on the question we're asking with a female athlete's study in particular or any changes we may see there, although we've also tracked estrogen in men, looking at some of the changes throughout a season, especially as they counter respond to some of the testosterone influences and things like that. Those are some of the ones we rely fairly readily on. The other one that I have found, the other grouping that we use pretty routinely is a thyroid panel. Unfortunately, a lot of times, if you just go get it tested, they might test like TSH and T3 or TSH and T4, ideally in that population. I like TSH, the thyroid stimulating hormone, T3, T4 and reverse T3. I think that's missed way too often. We'll also look at the blood lipids. We've got some really cool data in both athletes and in dancers, so like artistic dancers, so elite ballet performers. They often have higher blood lipids, but it's often associated with low thyroid. People forget that thyroid helps modulate and metabolize these lipids. If thyroid is not functioning appropriately because of, say, low energy availability or any of those things, we may be looking at a situation where we can see cholesterol rise. So looking at those markers tends to be very valuable and we've been using prolactin. More and more, I'm finding prolactin to be a very responsive stress hormone and much in line with cortisol. And in some cases, a bit more predictive for some of our studies for performance downturns. And it turns out the prolactin responds incredibly well to stress and it's fairly indicative of it. And so using that in conjunction with some of our other stress hormones, including the catacola means, another thing that we look at. But again, I can, depending on the financial resources of an athlete or an organization, that might be my ideal panel that we would look at, but we can scale it based on what's available. The one thing I don't do, and I get asked this a lot, especially by like strength coaches, like if you could just pick one marker, what would be where B-court is all? I'm like, honestly, like, it's hard to just pick one marker because they tell you different things. And so could you come up with a panel of, say, five to eight key markers? It depends on the question you're asking and how closely you want to monitor. We've probably boiled it down to about 10 to 13 that we can reliably use to track over time. There's others I like to use when we have the resources to do it. And I think in some ways, I would rather use those that have been indicated, implicated in health and performance, but use them on a very routine basis. So I would rather go for frequency over breadth of that panel because it gives me a chance to do something about them. So ideally, a perfect situation, roughly every three to five to maybe three to six weeks, we'd be able to track this, especially in season for athletes. Off season maybe we can go a little longer, depends on what we're trying to do in that off season, but we found a sweet spot around four weeks without it being overly invasive and overly expensive, but frequent enough that we can influence training and preparation. For some most of the things are blood biomarkers. My understanding is for cortisol, specifically either urine or saliva is preferred, which one do you like? I wouldn't say it's preferred. Saliva is easy. So salivary markers correlate well to the blood markers if we're looking at serum, but they're lower, right? So your concentration, you can't compare the concentrations in that case. So whatever you start with, you need to stick with because I can't compare those fluctuations across blood and saliva. So that's an important caveat to that. I prefer blood for cortisol simply because I get only other markers at the same time instead of having to run a completely separate assay or a separate analysis in order to do that, but we've used saliva a lot. We actually did a really big study with the Marine Corps looking at gender and aggression that we just completed. We had a bunch of publications come out this, but we were able to use salivary cortisol during recruit training in order to get that because if not, we're going to do blood draws on hundreds of the recruits all at the same time, but we could collect saliva on everybody at the same time. So some of it depends on which tool you're trying to employ, depending on what the toolbox needs are at that point, but all of them work. I think I've seen less that convinces me on the value of urinary cortisol. We use urinary cataclysmines though, but again, it depends on when you're getting first catch of the dead, yet how you're interpreting that over time. But mostly with cortisol, we relied almost exclusively on either saliva or blood. Gotcha. Coming back to the prolactin really quickly, you said elevated in times of, or is it yeah, it is, it is in way as the season goes long, we'll often see deflection in it as they're having a harder time mobilizing resources to handle the stress of the season in those that are starting to see a performance downturn, but by and large, yeah, we do see a rise in it. Interesting. I never heard that before. Cool. I'll look more in that. Anything else to say on this specific hormone before we move on to do maybe the next biggest villain that I hear about? No, I think cortisol has helped shape my career. That's what I started. The main hormone I studied and it just has followed me throughout my career. Yeah, love cortisol. It's good. It can be good, but we want to control it. Yeah. And to your point earlier about people trying to block it, I think I'm pretty sure that if you don't have cortisol, you die. So yeah, pretty much it's bad. Yeah. So insulin's been in the limelight quite a bit. And I think the probably Dr. Jason Fung's book, I think the obesity code, good book, maybe some issues in it and shared a lot of important, shared a lot of important insights and talked about how hyper-insulinemia can maybe really be the canary in the cold mind when we're talking about diabetes, obesity, that's something that's very important for us to talk about because in about five years, the expectation is that 50% of the American population is going to be in that category. And so that's scary. So with that, there's also the concept that insulin actually turns out, my understanding is the most anabolic hormone out of all of them. That and IGF1, I would put the two hand in hand, but IGF1 is insulin light growth after they go together. It's job is storage. So now it doesn't mean it's going to make you the most muscular a little bit of people think it'd be anabolic that way, anabolic is about growth, right? So insulin does an amazing job at story, that is its job. So let's talk about insulin. What is it that people need to understand about insulin and why should they not be terrified of it? Insulin and glucagon, okay? So those are your two counter regulatory hormones from each other. And insulin helps with the storage of glucose, glucagon helps with the mobilization of glucose in the system in order to handle this and keep blood glucose fairly stable. Insulin is going to primarily respond to a meal, right? After especially a high carbohydrate meal, but we also see a fairly significant insulin response to amino acids, especially free form amino acids versus a whole protein source. So insulin response to a meal, it helps with storing that. Now insulin can affect the storage within the muscle or with lipids, right? It can impact storage with the parasites. So insulin is important for helping to regulate that with glucose. But we don't want, and I hate to use this term, but it's the best way right now. We don't want too much insulin, what's too much? If you're at that hyperinsulinemic stage and it's chronic, we've had a problem. But I think there's been such an emphasis lately, especially with like continuous glucose monitors and stuff where it's a key to insulin stable. To be honest, we handle fluctuations in insulin just like we're designed to do that. It'll go up, it'll come down. That's not happened. The problem is when it goes up and stays up, and that can be actually funny enough, we were just talking about stress. We see that with stress as well, funny enough because of some of the influences we have on tissue sensitivity. But ultimately, we would like to be sensitive to insulin. And what we mean by that is not that you don't secrete insulin, but simply that it doesn't take as much to do the same job. And when we become insulin resistant, so we have to chronically increase the amount of cortisol that we secrete in order to handle whatever that nutritional load is and things like that's where we start to run into problems. But I think science is largely deep-bunked, the insulin hypothesis. That is the whole reason why we're fat. It's that insulin is associated with a lot of the behaviors at dietary behaviors that contribute to that as well. So is it insulin doing it or is it the factors that influence insulin that are doing it? And I think it's more of the latter, but certainly these chronically high levels of insulin are not ideal. But it also doesn't mean that we certainly don't want to block insulin, but getting a sense for in what's funny is what's interesting, like with the CGMs and with this emphasis on regulating insulin or whatever is honestly, even in the same person, the same meal doesn't even always cause the same insulin response from day to day. There's variability in how we respond to that, and that's okay. And so we start to look at how that influence occurs. But yeah, insulin is one of those things we should pay attention to. And if you have high resting insulin, that may not be a good thing when we start to look at it. But it often goes hand in hand with high glucose. And this is why, for example, looking at hemoglobin A1c as an indicator for these chronically high levels becomes fairly useful when we're looking at glucose regulation, but insulin's important for that regulation. What might influence those variations and that person, same meal, same person just different day? There could be other factors around the day in terms of the timing of certain things. There could be influences of other dietary components prior to that may still be changing the metabolic response. Some of it is welcome to being human. It could appear in a incredibly complex yet awesome system when you look at how we function. And so some of it will be influenced by, for example, in your workouts. Some of it will be influenced by your sleep. Some of it be influenced by the diet itself. So there are a lot of things that can do that. And it's also just the simple fact that these minor fluctuations are probably not a big deal. Like it's just simply our ability to be flexible in response and handle what's thrown at us. And when we start to become irregular in that flexibility or extreme in those responses, that might be where we have a little bit more of a problem. Because if we can make a bunch of small little minor adjustments to maintain homeostasis, the system loves that. It works pretty damn well. But if we start to require these big changes in order to get there, that's where we get a little bit more system disruption. How does our body respond with insulin to training, both resistance training or aerobic training? But during the training itself, it should go down, right? So basically, it was when I teach my exercise in the chronology class, we kind of start by saying, okay, I'm going to wrap the whole semester up like this. When you exercise, everything goes up except insulin, which comes down, done, right? They're, we're done with the semester. That was easy. And then it should not be high during exercise because exercise itself activates the glute four transport. So glute four transporters are embedded within muscle itself, and they're responsible for transporting glucose into the cell to convert it to glycogen or to shuttle it through from a bioallergenic standpoint through glycolysis and potentially on through oxidative phosphorylation. What happens is during exercise then, because exercise is, so glute four transporters are insulin-dependent transporters, they respond to insulin. For example, after a meal as insulin goes up, it will turn on these glute four transporters. They translocate to the surface of the cell, they can pull glucose out. However, those glute four transporters also respond to something besides insulin, which is physical activity, muscular contraction. And so exercise itself favors being able to pull glucose from the blood into the muscle cell itself to be able to use for energy, to use for storage after if we do that. But the reality is, in that case, that insulin goes down, glucagon should be going up to counter this and they tend to do it in balance with each other. So as insulin's falling, glucagon's going up. With chronic exercise, though, there is good evidence that with both resistance training and aerobic exercise, both of those increase our insulin sensitivity. They reduce our insulin resistance. So now, those same transporters, the receptors that are responsive to insulin are more receptive. They are more sensitive to its influence, so we don't require these big swings to produce the same effect. And that's why, for example, exercise has become a first-level treatment or intervention for type two diabetes because it helps manage blood glucose levels because of what it can do to insulin sensitivity. Yeah. Earlier you mentioned that your stress or whatever you're experiencing, we talked a lot about cortisol, can actually affect your tissue sensitivity to both glucose and insulin. I remember writing a blog post maybe 10 years ago about how there were some studies that I was reading where one night of sleep deprivation raised the average glucose level to like somebody in the diabetic range or predabetic range. Yeah. And I think those types of things have been demonstrated multiple times. What do we need to know about that? The tissue sensitivity being altered because of distress, as we said, or more sleep and that kind of stuff. Yeah. And it really does. And there's actually been, it's funny, you wrote that blog like 10 years ago when funny thing has been a couple studies that have come out recently showing what just one night of sleep deprivation can do to not only cognitive function and things like that, but certainly the other markers of metabolic dysfunction in terms of how we process and handle most of our food sources, macronutrients and things like that. And you're right, it resembles almost this sort of prediomatic state in terms of what we do. Now, what does that mean on a day-to-day basis? Ideally, you're never sleep deprived, but unfortunately in this society and among other things, it's going to happen from time to time. But I think it points to the problems with that being a chronic pattern because again, a day-to-day fluctuation in that, not going to panic and say, oh man, you only slept for five hours last night. I'm sorry, today we're going to start government forming, right? That's not how this works. But if you let that go on long enough, where stress is consistently high and you're not handling it, where sleep deprivation is a real consideration, or at least sleep restriction more so than deprivation, that's probably fair. You start to look in a situation where it does set the system up to become more resistant and less sensitive to these influences. I think that is one of the beauties to exercise, proper diet, proper self-care, is that we can actually change the sensitivity of tissues in a positive way to be able to prevent these massive fluctuations in hormones, especially arrest, in order to handle these things and recover from them a bit quicker. So yeah, that chronic influence is something that we would consider. Again, it's much like the HRB and the heart rate stuff. Don't let one day freak you out. Don't panic about everything because one day where these things changed. And I think that's maybe, it's a blessing and a curse to the way people are using CGMs, because continuous glucose monitors for somebody who is diabetic, I think are fantastic. For somebody who's not, we have yet to really see anything that shows there of any true value to them. And as a matter of fact, they may provide an older abundance of information that just gets really noisy and makes it hard to interpret. And I think the reality is in all this stuff we're talking about all, I think that the reality is, if you pay attention to too many of these inputs, you wind up with a lot of noise. And I think one of the hardest things to do in this area and maybe one of the things I enjoy about it, but I see being oversimplified through social media and stuff like that is, some of this isn't quite as simple as people like to make it out to be because you got to know the context around it and the other influences that go with it. And I think that is the reality. So yes, all these things start to play in the same sandbox when that starts to happen. What about you seeing it for a beautiful period of time as an educational tool? Absolutely. In that case, especially depending on who you're working with, but again, for an otherwise healthy individual or honestly, even for an athlete, I'm not a big fan. I don't think that it helps as much as people think. The people I often see promoting that are the ones that really think ketogenic diet is the answer to everything who think that insulin is the bad guy. It's this evil little demon somewhere that's doing all this bad stuff. There's a lot of stuff that I would probably utilize for educational purposes before that, given the burden at places. Not to say there's no value to it. I think I try to look at it from a sports science standpoint. I try to look at the big rocks first. One of the things that are really going to move the needle. To be honest, the fundamental dietary influences, the ones that we know work for performance, using select biomarkers to be able to track where your changes are occurring or where your deficiencies might be, those to me will be infinitely more powerful because they are getting at the core of the entirety of the physiology versus just insulin in this case. I think with the or even glucose and glucose modulation, not that glucose responses are important, but I can influence those a dozen different ways. We influence them with activity, we influence them with diet, we influence them with sleep. It depends on what level of noise we're willing to endure in that, but I think if employed properly and in the context of what we're already doing well, could be a useful addition. Would it be my day one? No. Now, if you're working with a type 2 diabetic or even a diabetic athlete, like a type 1 diabetic athlete, those can be absolutely life-saving, and they can then really help you tweak your dietary interventions around those athletes or especially around that type 1. But for an otherwise healthy athlete, I don't think that's where I'm going to start. Yeah, that's fair. I will say, though, just from the Hawthorne effect, if you have the resources, it could be a very powerful tool. Oh, no, I don't disagree with that. That's why I'm saying anything we can do to get people to pay attention to their behaviors. So to me, it's like when you talk about like fat diets, do they follow intermittent fasting, paleo diet, keto, blah, blah, at the end of the day, what they all force you to do is look at what you're eating, right? There's this factor of paying attention to your diet, and what almost all of them have in common is removing a lot of process stuff. So was it the diet or the impact of going on that diet that made the difference there? And I would say same thing with CGMs and things like the same thing with ORA rings or whoops or anything else is if it makes you pay attention to some of your behaviors, that can be a really good thing. Just we need to make sure that we are using the technology and not that the technology is using us, right? So your decision making around that needs to be within the context of how everything else is, right? Because there's been days like on the aura, like polar whatever, you're going to die today if you work out, and I might have the best training that I ever have, and I'm like, yeah, I knew I felt fine, like I felt good. And so there's just simply days where, you know, as an athlete, as an avid exercise or things like that, pay attention to you as well. Don't just go off the metrics, use those in combination with the rest of the way. Because there's some days too where I'm like, man, I got four hours of sleep last night, because you're ready in this level is fantastic, and I am not training today. I'm exhausted. That is a bad idea. So again, using a little bit of common sense with this, use the technology, not the other way around. So do you think people are intuned enough for their bodies that could be reliable? And I especially think about college athletes. I think about myself and college. I could sleep four hours a night every single night, I'd be ready to go the next day. And of course, when you're 20 years old, like that doesn't affect you as much. I just, I don't find it when I see people, when I'm talking to people that they are really understanding what's going on with them. And you know, it's a great point and it's because we're not helping them understand what to listen to. So what I mean by that is we've worked with athletes over the years, and it's funny. I step back and we often make this assumption college athletes, that must be great to work with. These are high fours. I'm like, dude, some of them know nothing, right? And so we would be starting to do like sport nutrition stuff with them. And we realized they don't know the difference between a carbifact and a protein, like we're start with fundamental nutrition, you're not even going into the differences in carb sources. You're disability. This is a carb. This is a protein. Okay. Good. Let's work on that first. What we have generally found is athletes often exist in a state of fatigue without knowing that's not normal. Okay. And so what we'll typically do is, and this is where some of these other markers become very useful to educate them. I love how we've been able to use training load, for example, to help athletes understand what they need to replace, right? When we were able to get female athletes to start associating their training load and clork expenditure, not with, oh, good, I'm going to lose weight with, but with, oh, I need to eat to replace this now if I want to perform amazing response, right? That is like, you're now using their own data to help them understand. And that's how we've used biomarkers. We use their data to help educate them. And what would happen is, if you do the right things, if you pick the big movers, the big rocks, what's funny is the number of them that will come back and be like, I can't believe how good I feel. I didn't realize, I just thought that the way I was feeling was just because I trained hard. They're like, I don't have to be exhausted all the time. And we've had athletes. It was funny, actually, one of the athletes that Michelle works with. So for the listeners, my wife's the director of Olympic sport nutrition over at the University South Carolina Athletics. Anyway, one of the track athletes she was just working with, just won a silver at worlds. And he didn't realize how much better he could feel, but he made the commitment to wanting to do this. So he started to pay attention to how he felt after doing these different things from a dietary standpoint, from recovering from his training and all the stuff. And he showed up big smile on his face to show where his metal winning got back because it made a difference. So I think what's key in this is helping them understand what to listen to because you're right, man. I think back to college, the number of games and practices that I was functional for probably a small miracle at times, but I think at that age, you can play through a lot. What has been really revealing to me is especially the more I worked with pro athletes and pro teams. The athletes that always had the most questions were the ones that were at the tail end of their career. And their question was, how do I get another year? How do I get two more years? How do I get one more contract? And what started to happen is the younger players started to pay attention to that a little bit because the older players could be like, you don't understand. There was a lot I could get away with when I was your age. I wish now that I would have known more of this than I would have actually probably been even better. And so I think we're seeing a shift there, but I think teaching these individuals to start to listen to their body and pay attention to how they feel is something we don't do enough. We throw numbers at them. We talk to the coaches and stuff. And I think sometimes with the athletes, everyone wants to just have that conversation of, hey, how are you feeling? You know, how are things going? What's going on? And using their own data to help them understand where they're at their best and where they're not? That's why to your point, CGM or otherwise, if we have a tool that helps them dial in and focus on them, we can help them start to understand how did you feel during this period of time, too? How did you feel when you ate this before a game versus this before a game? It's just getting them to pay a little bit more attention because I think you're right without that guidance, though, it's easy to go on and be like, yeah, you can go through anything. And I think that what we're trying to get them to do is one thing I've learned with athletes and with military operators, like if you're working with special forces, those guys are unique, right? Because at the expense of anything, they will make a mission. That is their whole goal. What we want to be able to do is help them do it in a way where they come home alive. And in the case of an athlete, where they feel good being able to do it as well, and they can really maximize their potential, what I found is, that's funny. One of the definitions of overreaching is that you should see a performance downturn. I've generally found that as not accurate because there are a lot of things that an athlete or an operator will find a way to cut through. It just feels a hell of a lot harder than it should or than it used to. And so it's that dialing into what's happening to performance and how you're getting there that I think we need to pay a little bit more attention to. Yeah, to your point about athletes and I think the hitting the genetic lottery probably helps a lot. I remember. Absolutely. If you want to be an athlete, pick your pair as well. I remember you listened to an interview, DK Meccaff, then maybe a year or two ago, and he talked about, oh yeah, like he doesn't eat his first meal till four, which is like a drink. And it's not a meal. It's like a Grande latte or something from Starbucks. And then he eats like two bags of skittles and then he goes to practice and he comes back and he has like another latte. And I was just thinking, what the hell is a C-hike staff doing? I don't understand how this he's still performing at a level like that. So you hit on an interesting point. And so here's the other thing to throw into this. Number one, and I'm not saying DK's lying, but athletes do lie. And a lot of times, and I've worked with athletes that have done this on purpose, they will actually lie about what they're doing. So they're opponent thinks they're doing something else or that somebody else tries to do the same thing and it just hangs up. But that's not what they're doing at all. It's hilarious. Second thing though is I often look at these things and you get like these younger athletes or just anybody inside like soons, they say they only McDonald's and they do all this. And my thought is always man, how good could they be if they didn't do that? And so people look at us, you don't have to do that stuff because look how great they still are. And I look at it as, yeah, and I've seen this with some athletes over time where absolute rock stars, especially on and then later in their career, they're playing my injuries. And you look and you go, yeah, because you were able to do a lot based on that genetic lottery early on, that might only last you for so long before systems start to change. And so how do you keep that car running at its optimum? You can only put crappy unleaded gas in that Ferrari for so long before it starts to backfire. Right. And so it's, I think it's an issue of, I always think that is the slippery slip to go down where they look how good they did it and yet they only do this. And my first thought always turns you in my God, how good could they be if they didn't? Right. That's just a scary thought in some of those cases. And then there's other times where with certain athletes, you're like, man, I ain't going to broke what's work. I'm not going to break it. If it's not broken, I'm not going to fix it. We'll just make a few little tweaks, but you also want something they're comfortable with. So I'm going to complete overhaul and make them hate the process because they're so restricted on what they do. You got to meet where they're at. Coming back to the assessment and testing, do you ever use OGTT as part of the assessment for insulin or? Nothing. We've done with athletes. No, we haven't had the need to be honest. Okay. Okay. Because I'd be curious, because I think that the biggest thing you highlighted, it's the response to meals is what we're really curious about. So do you find that the IGF-1, is it IGF-1, or do you check on IGF-2 as well? No. We only use IGF-1, but we use it in a chronic sense. So looking at it's upstream from the stimulus itself in terms of, and the problem with IGF-1 in circulation is that you don't know whether it is liver or muscle derived, and it can be both. And the liver derived IGF-1 is typically the one that's going to be responsive to the growth hormone stimulus, IGF-1. And we also see this even with BDNF, because there's also muscle derived BDNF. Where that IGF-1 is coming from doesn't really get distinguished in the bloodstream. But the overall IGF-1 response, we have found some pretty interesting correlations with strength performance over the course of a season and changes in IGF-1, especially in female athletes. And we've also found some pretty profound responses in, or changes, I'm sorry, in response to high-training volume. Yeah. So let's shift to talking about growth hormone. Actually, in fact, I remember you talking about, I don't know, 2009, but it's the class that we were in. That, I mean, growth hormone, pulsatile hormone, we can't really measure it. And so we actually check IGF for that. So can you, does it give you, does it have a dual purpose in that regard that you can also check your chronic growth hormone state for that? Yeah. And IGF-1 can be used for that. But also, again, since we don't know necessarily where it's coming from and whether it was GHG influence, we'll typically still measure GH. The problem is if you miss the pulse, and so one of the things we try to do is if we're looking at growth hormone from a recovery standpoint, we don't measure it in and around the training. Right? Because that's that training about is going to have a pulsatile influence on the growth hormone, and that can influence it. So we try to control for time of day and more of a chronic type of measurement. And like I said, it's been interesting because I think across, God, I don't even know how many studies now, we rarely see a chronic change in growth hormone with the male athletes, what we do in the female athletes, and actually resting levels of growth hormone in the female athletes that we've tested are between like four and eightfold higher than the male athletes in most cases. And so they part of that is probably accounting for why they are able to respond to training with increased muscle and things like that because they don't have the same testosterone influence that the males do. So there's a bit of a trade off there. There at least that's the speculation that I think makes reasonable sense when you look at how these things correspond to the ability to synthesize proteins and whatnot. But again, there's more to that. There's a mechanical stressor factor and all that other stuff. But within the hormonal milieu, the GH part is pretty interesting, but growth hormone also just plays an important role in other recovery factors too in terms of tissue remodeling and repair in collagen, synthesis and stuff as well. So I don't want to dismiss it. And I do think it's an important hormone. Yes, it's acute influences. It's interesting growth hormone responds well to stress too. So under stressful conditions, we'll typically see growth hormone go up and would seem counter intuitive because like that's certainly not going to be an anabolic scenario. But what growth hormone is doing is it also was a fairly potent, lipolithic hormone. And so it does help mobilize fuel resources to potentially be able to spare protein in that case. So there's dinner play with that and other hormones in that case. Yeah, I think most people, when they think of word hormone, they're thinking baseball, they're thinking athletes using it for recovery primarily to heal back from injuries. And I think people miss the importance of it's role in metabolism, kind of like you have. Absolutely. So from that lens, what else should we be aware of? And what? I started this conversation by talking about this individual who was talking about the acute effects of growth hormone to training. Are there any strategies with respect to our training that we could deploy and modulate it to our benefit? Not really. I think we put too much emphasis on that. I think there is, I think there is some value in understanding the acute hormonal responses to training, but realize they're very short lived. If they're doing anything, they're serving as important signals for these other translocation factors and the other things that go on with the protein synthesis, but acutely, so much of what we see from exercise is more the mechanical stimulus than even the hormonal. Not that the hormones don't matter, and especially chronically with what we might see over time. Certainly we block growth hormone, block testosterone, that is not going to be a pretty situation. But ultimately, basing your entire, so here's the funny thing, the lifts that tend to be the things where we see this increase in growth hormone also happen to be the lifts that would form the foundation for most of your strength training in the first place, or even hypertrophy if you're looking at bodybuilding and whatnot. So it's not so much necessarily that the growth hormone is what's indicating that's why it's effective. It's that growth hormone responds to stress, and you're applying this relatively efficacious stressor. It works to increase muscle to increase strength. So it's like dumb luck into it, so somebody can be like, hey, if you look at these exercises that primarily increase growth hormone, and you make those your priority in your training, you're going to get stronger and it's a no kidding, because it turns out most of those are squats and dead lifts, bench presses to some degree, a lot of whole body multi-joit type of movements, wow, genius. So I think it's like twisting the narrative a little bit, and it's funny because the pieces of information are actually correct, the why is not. So it's yes, those are the things that make growth hormone go up, and yes, those are what make you stronger, but it's not because of the growth hormone that's having. But it's that growth hormone is a signal for what that particular exercise or exercises or exercise about is really doing to the system, if that's the case. So again, paying attention that the pulsatile nature of it, when we may miss its measurement and things like that. Again, all always important, but that's not to dismiss the role of growth hormone, right? Growth hormone has important physiological ramifications within the human body. Growth hormone, and this is why as we age, as growth hormone declines, we see these losses in muscle mass, we see increases in body fat, is it all because of growth hormone? No, cause there's other stuff going on too. But certainly that decrease in growth hormone is helping case. And I think people also need to be careful not to conflate exogenous and endogenous growth hormone. So somebody taking growth hormone versus the growth hormone response to exercise are not the same thing with testosterone, right? So people are like, oh, but people that are taking testosterone, clearly they have more muscle. So testosterone does matter. But when you're taking these high exogenous levels, it's above and beyond what your system would produce. Again, you're going to be able to support muscle. So we know testosterone can make a difference there. How much of a difference does it make within an otherwise optimal or normal range for say a young healthy male? Probably not a time, but again, not knowing receptor sensitivity, not knowing free versus total, things like that. Hard to interpret. I don't want to throw the baby out with the bath water though. I think there's some people that have just bought into this whole thing, researchers that are like just completely dismissing hormones as important in muscle growth. And I think that's missing it too, because a lot of those studies, they've measured the hormones in response to single exercise about they train them for eight or 12 weeks and they go, oh, look, it wasn't predictive of how much muscle they ate. I'm like, yeah, because every workout is going to be a little bit different. I would be really curious what that looks like when you accumulate those effects, because anybody that lifts on a regular basis knows that not every workout and every day are equivalent. There's some that are better than others getting stronger. And so I just, I think we may be gone a little too far in the, it doesn't, I think one point where like it matters so much, that's the main driver. And now we've got to, it doesn't matter at all. It's all the mechanical stress. I think the truth is somewhere in the middle where the mechanical is driving a lot of it, especially early in a training program, but the hormonal response still plays a role. It's just not as big as we probably thought it was. What about lactate training though? I remember reading a study way back when, and this is probably when I was in college about how training above a lactate threshold in our power aerobic athletes, as you like to call them, specifically more than 10 minutes had a significant response greater than 24 hours. In those instances, it's not necessarily squat, steadily, it's that kind of stuff. Now we might be on a bike, right? Yeah. Absolutely. That you've worked with. Hey, it's awesome. Yeah. Lactate, lactate is a cool molecule in a very, we could probably put it in there with cortisol and insulin in terms of being misunderstood. We have a much better understanding now that lactate is not a bad thing. Lactate itself is a fuel source, and the ability to metabolize lactate, especially following that workout, to reconvert to glucose to the curry cycle of things like that's a good thing. The ability to generate lactate in that power, power endurance athlete is actually an adaptive advantage, right? To be able to get to those levels to be able to go that anaerobic, to generate that level of lactate. It's going to be heavily dietary influenced, but if you don't have a high kind of carbohydrate intake, but you're not going to see as much lactate accumulation, things like that. But I think what's important in the lactate conversation is not only production, but also clearance in terms of how this shows up. But I think lactate does serve an important biochemical signal for the strain on the system. It can cause these downstream effects for mobilization and signaling from an effort standpoint. But yeah, more than anything, I think understanding lactate as a fuel source and understanding lactate as an indicator of some of the intensity factors can be a super useful way of looking at it, because I think for far too long it's been looked at as a waste product. And I think, too, I still hear people really misunderstand it. I've heard trainers tell their clients, like the reason you're sore the next day is because of lactate, typically they'll say lactate acid, which is even more of a problem. Not anyway, but you're not sore because of the lactate. You might be sore because of the work that caused lactate to increase. And I'll put it this way, if you're still sore from the next day, please get to an endocrinologist because there's something really wrong with you, lactate should not stay elevated. Oh, like lactate clearance usually occurs within five to fifteen minutes in almost every study we've done. Why might it increase growth hormone response, though, in some of those athletes that I was talking about? Honestly, a lot of it's the signal. It does appear that from an upstream standpoint in terms of growth hormone, releasing hormone, because lactate can also work at the level of the brain, right? The brain has the ability to sense this. So in many ways, it's serving as an indicator of intensity. So I guess, while lactate itself has been, at least in some animal studies shown to influence growth hormone response, also realize that the same training that produces a lactate response tends to also be much of what produces a growth hormone response, right? So it's a little bit of everything in there. Again, it's a challenge with looking at any one thing in isolation in the human body because there's such complex interplay. And it's honestly one of the things that drew me to the endocrin system initially was I loved how complex it was, but also how redundant it was, right? There are checks and balances and failcees in place so that we don't follow part because of one thing not working right. It's amazing how good we are at doing that. But because of that, it's important to be able to look at those things together so that we're not overly simplifying and otherwise fairly complex organism to do this. But I also don't think we need overcomplicated because I think that it makes some of the interpretation very difficult, but it's also not, I don't know, I guess in some ways we could do like an endocrinology for dummies kind of thing, but at the same time, we have to be careful the pathway we go down with that because of what some of the interpretations might be. And certainly the things that we might see with exercise, overreaching, over trading, whatever it is versus a true disease state, it's interesting because there are some interesting parallels, but very different repercussions, right? And very different long-term implications in terms of recoverability versus a true dysfunction that we might be looking at in that case. Amazing. Sean, I'm looking at my notes here and we're not even about 50% even talk about the sex hormones or catacolamines and just some of the future directions that were preservation of muscle that I want to talk about, but I know a man, if you're a game, maybe we'll just park it here and have you come back for a part two because I think that people can really upset if we don't talk about the sex hormones. Everybody wants to know about testosterone. Everybody wants to know about that. So let's do that. Right now, if you want to talk about testosterone. Let's do it. Let's do it. So briefly talk about the sex hormones, right? It's testosterone. Estrogen, testosterone, you had mentioned all very important, but I think you highlighted estrogen is really important in male physiology as well. What should we understand about these particular and also maybe if we can focus on the role of estrogen in males and then the role of testosterone in females because I think people don't understand that they're necessary in both. Yeah. And so I think at one million, first of all, three of those are steroid hormones, right? So again, much like cortisol, they come from cholesterol. Cholesterol is the mother steroid in this case. So because of being steroid hormones, their half-lives also differ from peptide hormones. Their rate of appearance is a little slower, but they hang out for a little longer. They will use transport proteins to move them to the system. So this is where we start to look at three versus bound versions of this and with the free being the more bioactive. But when we look at it overall, especially taking testosterone, so obviously it's an androgen, it's an androgenic hormone, right? So it's responsible for a lot of the masculinizing effects. Women have testosterone as well, just in much, much lower circulating levels. And much on the women's side, in the men, most of our testosterone is derived from the testes. In women, you can get a lot of that from the adrenal gland, right? So the adrenal cortex also produces your androgen, your mineralic cordicoids, your glucocorticoids. And so in them, that can be a good source of this in terms of what we see. And in women, honestly, especially in some of our soccer studies, we saw a significant increase in testosterone coming out of preseason because of the training volume, right? So it is also responsive to the need to handle this high level of demand physiologically. And so I think when we consider how those things fit together, they really do start to mesh. And in males, obviously, look, we hear often the importance of testosterone to males. And it is, right? And it's also understanding that there's reached physiological and super physiological levels is important in understanding using testosterone versus the testosterone you naturally produce. And I think we should pay attention to this. Now, is there some magic number of what testosterone should be? No, there are these normal ranges, though I'll be honest. The more and more I've worked with athletes, if you're towards the low end of normal function, does not seem to be nearly as good as if we can move you up towards the moderate to high end of normal. So even within normal range, there are differences in this. And I know some have argued this that it doesn't really matter. But I think those have been poorly done studies that they're relying on. And it's also not looking at outcomes that would be, let's see, highly important to athletes, for example, in terms of where we see that sort of optimization and strength in overall performance. So I think those factors are pretty critical to look at. But I think the other thing, too, is estrogen. So estrogen also tends to be cardioprotective. So estrogen plays a pretty role in cholesterol accumulation. So if we're looking at atherosclerosis, right? So there's a protective function of that. And in males who use animal exteroids, especially anabolic androgenic steroids, if they suppress their estrogen too much, especially if they're taking an antiestrogen or the entire rheumatase of things like that, that can bring estrogen down to a level where that might precipitate some of these cardiovascular factors, right? The ones that are less than ideal under those circumstances. And the other thing, too, is a lack of estrogen in men can actually kill sex drive, too, right? So this is important for factoring the soap. We don't want to just look at what your testosterone levels are. But what are also your estrogen levels? Because the flip side to that is in a lot of males, if you take animal exteroids, your estrogen levels can also be very high if you get a lot of aromatization, right? So if you get a lot of conversion because of the excess testosterone, so understanding that interplay is very important for understanding the overall effects on the body as well. But from an endogenous standpoint, what we make, right? We know that these are responsive, especially estrogen, or I'm sorry, especially testosterone, to certain high intensity types of activities and stuff. But again, just having this little blip in testosterone in order to have a more chronic effect to this, your basal levels have to go up, not just this one little one hour post exercise magically creates all this other muscle. There's these other 23 hours to account for, right? So I think that it's an important signal for some of the other pathways that are involved in protein synthesis, but I don't think it is the big dog. We probably thought it was acutely versus some of the chronic effects, but acutely, I think the mechanical stressors and some of the other factors are probably significantly more important for the adaptation of that training. But overall, I think that the role that it plays and I think that understanding the things that can decrease testosterone, because we cycle, we circle back to what started this stress, right? We're talking about cortisol. Stress can act at crush cortisol response, or I'm sorry, it's crust testosterone response. Other high stress, we start to see these testosterone levels fall, dietary influences can play a pretty big role in testosterone as well. And so especially if you were under fueled as a male athlete, this is one of the things we look for in our athletes as a matter of fact. And there's been a couple athletes we've worked with over the years where the decline in testosterone was really one of our big indicators. And once we finally started to dig deeper into their fueling strategies and how many calories they were eating or not, that was where we're able to make a pretty big difference. And that rebound of testosterone was really an important indicator, and their performance also went along with it, right? So we know it ties in from that standpoint, but again, I wouldn't put too much emphasis on just the acute effect. If anything was interesting, we had a study in wrestlers that looked at this, but the acute effect of testosterone may be more related to aggressiveness in sporting situations and also a higher likelihood of winning, but the way it's typically talked about in terms of its influence on muscle growth and things of that, I got to be honest, it's probably more of a drop in the bucket acutely than what we see for mobilization for wins and losses in like combat sports and grappling and things. That was a cool study. But anyway, so I think overall looking at those sex hormones and then on the female side, that regulation of those sex hormones and normal menstrual variation over the cycle is something we need to pay more attention to. And I think that female athletes need to understand that not having your period is actually not a good thing. Right? Like we want normal menstrual function as well as we can define normal in that capacity. And so the roles of estrogen and progesterone and that and their normal fluctuations through the cycle are something we need to stress more. But I think we'd probably put a little bit too much emphasis, not we, the collective we doesn't apply here, certain social media influencers have put a little too much emphasis on using faces of the menstrual cycle to guide your diet and your training and stuff. We're not there. And honestly, if it does have an influence, it's fairly small and I think it still goes back to the conversation we had about that monitor how are you feeling kind of this auto regulation sensing yourself. Yeah, there's certain times during that menstrual cycle where you don't feel as good or especially pre-menstrual with cramping or other symptoms, that's going to impact your performance. It's not so much about the hormones, it's about the symptoms that might go with that. So I think we're in the early stages of understanding more about that. And I think there's some great researchers digging into this. We've done a couple of studies on this as well, but I think understanding these hormones influence and the fact that their normal physiological pattern is important to preserve. We want to make sure they are operating normal, right, that we're not getting these massive fluctuations or dampening that response and that applies to either the female sex hormones or the male sex hormones. And I think that's the reality too that's often lost in this. I will say one thing that I think is particularly interesting. Testosterone plays an important role, especially in fetal development when we're looking at some of the receptors that basically dictate power response later in life. So even sex differences due to testosterone receptor exposure, actually make a difference in development there. And it's why we start to see some of these things show up later through puberty. When those hormones start to increase, there's more receptors available in the male athlete in order to do that and it can drive a lot more from a performance standpoint. Yeah, I love it. A couple of things to follow up on there and to your point about estrogen and how critical it is for cardiovascular protective benefits, bone health, that's another one. Absolutely. Absolutely. We can get into that in females, but also in males, I would say loss of muscle mass particularly with these antiretric drugs is a bit of an epidemic right now. Yes, I agree. And so something to pay attention to, it's actually one of the reasons, right? So clomathine citrate used to be something people would use to help particularly in somebody trying to preserve fertility to increase their levels of testosterone. What we learn is that up to 40% of men completely destroys their libido because it works on is a selective estrogen receptor modulator and so that's something important to know. It doesn't happen to everybody, but can be a drug that completely defeats the purpose of trying to raise with levels if that's a concern for the individual. And that's why you're going to see more people gravitate back towards lower dose HCG. Because it does not have that effect as someone tends to upregulate the LH and FSH response in that case. Yeah, very expensive though. Very expensive. And much more difficult to get a hold of. And then to your point about the dietary influences, I think I remember recently coming across a study, Heinzelman, forget his last name, Fantaski, talked about the recent study looked at a minimum of 15% or maybe even 20% of a calorie should be coming from fat. I think this is, again, fat or caloricly dense. And if you're absolutely trying to cut calories, if you're on a GLP one where you have no appetite for fat and your fat drops below a certain level, like that's, again, going to have an effect. It could be one of the pieces of the puzzle, like we've talked about. This is all very complex. A funny story. I'll share it with you, Sean. And I believe listeners with this exercise physiology class, I remember. So this is what 2009, 2008, some time at that point. I remember a picture of you, you put a picture of Mark McGuire and you were talking about Andersine Dion and you had the whole metabolism until Andersine Dion and you were making the point of a Mark McGuire about that. And I just remember seeing cholesterol upstream from that and I was like, yes, for the next I don't know a couple of weeks, maybe even months, I was just going home and just smashing hard boiled eggs. Yoke included, but especially the yoke, just trying to do it and man, I'm just wondering what I did to my lipid markers at that time. But that's how stupid people can be and that's how stupid I was at the age of 19 years old. And I think you'll leave with you guys. That's how simple that is. So thank you so much, man. Hopefully we'll find time to come back and talk about thyroid hormones and like I said, I'm really interested in talk. I want to talk to you about these my statin inhibitors that I think is going to be awesome, man. Thank you so much. You bet, buddy. Good to see you. And yeah, happy to connect again. I think there's a lot more fun stuff we can talk about. Yeah, the GLP one of the myostats and stuff is interesting. Yeah. Thanks for listening to the other episode of medicine redefine. If you enjoyed this episode, please be sure to check out some of the additional resources in the show notes. Please also check out our social media platforms where you can find more content like this. You can follow us on Instagram, Twitter, and TikTok at Med Redefined. We also want to thank our team for the production of this podcast, Arita Yepurian Social Media, Zana Bligmani, our research, and Sarah Hahn for Newsletter. Oh, and if you want to get similar bite-sized information delivered to your inbox every Sunday, please be sure to sign up for our newsletter. Also, if you enjoyed the show, please be sure to subscribe, review, and share with anyone who you think will gain value from this as well. Now, time for the ever-so-important disclaimer. 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