Welcome to the Empirical Cycling Podcast. I'm your host, Coley Moore, joined as always by my co-host, Kyle Helson. Thank you, everybody, for listening. And if you're new here, please subscribe if you like what you're hearing. And if you're not new here, please share the podcast. Give us a nice iTunes rating. And also, we're ad-free, so if you'd like to donate, empiricalcycling.com slash donate is going to be great for that. We've got some show notes up on the website. We do have show notes today. I've got a couple of papers linked up there. And if you have any coaching or consultation inquiries, please shoot me an email, empiricalcyclingatgmail.com. We are always taking on clients, and we're always ready to do a consultation, hire us, and we can ask you questions, look at your training, et cetera, et cetera. So if you have any questions or comments, also shoot me an email there or DM me on Instagram. I usually check those once or twice a week. That's empirical cycling. And that's where we also got the questions for today's episode. And I also do a weekend AMA up there every weekend. So give me a follow there on Instagram empirical cycling. So this is our next Wattstock on the adaptation series that I have been talking about and thinking about for a very long time. So this bit of this series is actually not a smart thing to undertake for a couple of reasons, but we're going to do it anyway. First, I feel like it's going to be informative no matter what, because there's a ton of research on some of the things that we're going to talk about, but not a lot of it is absolutely ironclad and conclusive about the ways to alter training to enhance these things more. A lot of it goes to just... Don't train dumb and you're going to be fine. And today is one of those things where we're going to go through a couple of ways to try to big brain what we're talking about today. And you're going to see exactly what I mean. So because of that, there's a lot of ways, a potential for misinterpretation. And if you have any questions, please let me know because... I do see a lot of these things come back to me a couple of months or weeks or years, even after a podcast is out and somebody says, oh, what about this thing? Did you say this conclusion? And I don't think I did for a lot of this stuff. So clarifications, questions, I misunderstand things all the time too. So it's not a big deal. Here's another reason. Oh, sorry, go ahead. Oh, no. And yeah, I've had people message me and stuff like that or ask questions and it's great. You know, if it's like, oh, if it's something we, you know, even if it's something that wasn't like the main takeaway, like, oh, there was this one detail you mentioned, like, oh, yeah, yeah, that's X, Y, and Z. And it's nice to know that people are listening, listening close enough to ask questions like that. Yeah, the very detailed questions I always am a little surprised by because on some level, I don't think I've ever listened to anything that deeply. But on another level, when I really get into something, I listen extremely deeply indeed. And I've, I'm, I will read the same paper or passage in a book like six times, 20 times, you know? Um, so, so the other reason that this is, uh, this is silly to do, uh, because it's the reductive nature of science because when you narrow down a signal, it ignores a lot of the other signals in a muscle that are simultaneously activated. You know, it's, um, it's sort of like the, the metabolic pathways thing where you, if you look at like a time course of what fuel like, you know, ATP, creatine phosphate, glycolysis, aerobic, like what's the time course in all this stuff. And a lot of the time it's like X is, you know, it's phosphocreatine from like zero to 10 seconds or something like that. It's not actually, it is not actually like that. You know, these things are co-activated and there's a lot of stuff going on at the same time in muscle because evolution is very smart, as I've said many times on the podcast and many other people have said before me. And so when we think about narrowing down on a signal like calcium, like we're doing today, it is one of a host of things that's going on. And when we step back, there's only two real main adaptation types that muscle experiences anyway. One is aerobic slash endurance, and the other is strength. Like, do you want to maintain? like homeostasis and ATP longer, or do you want to move heavier shit? Like it's, it's, it's pretty simple. It's a pretty binary thing. And there's of course a gradations between all that stuff. But when we start digging down, it, it does kind of miss the forest for the trees when we focus on what's this tree. So, and so when we think about adaptive signaling and we think about training, And if we think about calcium signaling today, and if we modify our training to take advantage of this, and then we add in a little bit of race specificity, honestly, it's going to get you a lot of the way to a really, really good training plan. So keep in mind that we are going to be discussing... things while ignoring other things in this series. But it doesn't mean that overfocusing is going to be beneficial, because that's something that I have certainly done. And I think occasionally people listening to the podcast have done, not everybody, obviously, but occasionally a couple people have. And I have actually been guilty of it, you know, writing the podcasts. So I understand that. But I think the reductive nature of stuff is just kind of the nature of science. I mean, isn't it? Yeah. I mean, you, I think you tend to focus in on the things that are like easy or, or, or more straightforward to grasp. Like there's always the, it's always difficult to explain concepts and anyone who's. spend any time around like a, uh, like a four-year-old knows, like you can just keep asking why and why and why, and you have to like peel back these layers and layers and layers. And you can ask why until you outstrip your, your own knowledge. So, so focusing in on what you do understand and the simple things and drawing analogies is the way that you actually learn, learn kind of how things work or gain an intuition on how things work. I know. Isn't it great when a four-year-old makes you realize just how stupid you are? It's like, holy crap. Four-year-old just showed me I don't know shit. Okay, cool. So today, okay, we're talking about calcium. And we may very well get to some limits of knowledge in this podcast, or we may not. We're going to try to stay within bounds this time, although we certainly have gotten to the limit before. So what's the role of calcium? in muscle cells. Well, the main role that everybody thinks of, there are others in terms of like when calcium floods into a cell, it activates certain proteins because, oh, we're clearly doing exercise. So it has certain effects in like the Krebs cycle, for instance, those proteins, it'll like activate them more, et cetera, et cetera. But the main thing is when an action potential comes in, when our brain sends the signal to our muscles, hey, contract, it triggers the release of calcium from what's called the sarcoplasmic reticulum. And it literally just opens the floodgates and calcium floods into the cell. And it raises the concentration in the cell by quite a lot, basically an order of magnitude concentration. And it binds to tropomyosin, which changes its shape and allows myosin and actin to bind. And that consumes ATP. And that's a contraction. And so when you relax and the signal stops, the calcium is brought back into the sarcoplasmic reticulum, the contraction stops. And in fancy terms, in academic terms, it's called electrical mechanical coupling because it turns basically an electrical signal brought about by electrolytes on different sizes of a membrane, which creates an electrical potential. change and we get a signal, it says, hey, it's time to do mechanical work. And we've got things that do mechanical work. So I actually think that's actually pretty cool to think about. Right? Yeah. It's always impressive the ways that your body is able to turn sort of follow the laws of thermodynamics and turn one type of energy into another. Um, because, you know, you started off with like breaking down molecules of sugar or fat or protein into, you know, some of it obviously gets turned into heat, but then, but then you, you, we've talked before how you drive this chemical potential so that you can get work out of it. Um, and so you're turning like, you know, a burrito into, into building blocks or energy, potential energy, and then using that potential energy to. you know, stay alive and do work and all that stuff. I always think it's kind of cool. Yeah. Yeah. I mean, that, that was why I was so fascinated by biochem when I got to school is it answered all the questions I had when I was growing up. Um, and it's still, it fascinates me to the same degree. Um, so I guess I'm, I'm fortunate that way in that it's, um, it, it proves a little bit useful and stuff like this. Um, so we've already discussed calcium and adaptation a bit in Wattstock number 28. And, uh, that was the one where we looked at high intensity interval training. Um, uh, the title was ranodyne receptor fragmentation and sarcoplasmic reticulum calcium leak after one session of high intensity interval exercise. And we've got the show notes up at empirical cycling.com slash podcast dash episodes. So, um, so you can go check it out there. Of course you can go. Check out WatchDoc28 also, where we discuss this study in depth. But basically what happened was they had people do 30-second efforts with four-minute rests, max efforts. And the gist is, if you're not very well-trained, those high-intensity efforts will lead to a ton of muscular aerobic adaptation. Why? Because you actually, when you're not that well-trained, you actually fracture the reanodyne receptor. There's damage done to it. And that's the muscle's channel to release calcium from the sarcoplasmic reticulum. So they also looked at well-trained endurance athletes and found that the fragmentation and calcium leak did not happen. They did not get the same adaptive signal. So the authors note that the fragmentation and leak was likely due to reactive oxygen species brought about by aerobic metabolism. which we've also discussed before on the podcast a couple of times. And so the well-trained people express more antioxidants like glutathione and all that as an adaptation to the endurance training. And Kyle, why would all this happen? So why would endurance athletes express more antioxidants in their muscles as a consequence of aerobic adaptation? But why also then therefore... wouldn't they get the extraorbic signaling, right? Because they're not flooding their cells with calcium so much? Yeah, so if you're – we've talked about this before. Oxygen is – corrosive is kind of the wrong word. Anyway, it can damage – like free radicals, oxygen. You can take a lot of oxygen when you exercise for obvious reasons, and you end up creating a lot of ions. that are within your cells. And so when your body cranks out antioxidants to sort of stop this oxygen from, oh God, you can't use the word in the definition, but your antioxidants prevent oxidation or oxidization. Yeah, oxygen steals electrons, basically. Leo the lion says, ger, lose an electron. Sorry. I actually forgot about that demonic. Yeah. So basically, like aerobic adaptation, it helps our, like we've talked about many times on the podcast now, like we're trying to maintain homeostasis in the muscle. And it's not just about ATP. It's about also preventing things that happen. Like when you are processing a lot more oxygen for a lot more aerobic metabolism, the consequence is you create a lot more reactive oxygen and nitrogen species. That is the thing that happens that fragments the sarcoplasmic ranodyne receptor on the sarcoplasmic reticulum and causes the calcium leak in untrained people. So this is one of the reasons, one of the many reasons, that after a little while, high-intensity interval training doesn't really keep making you faster. Like if you keep going and keep going and keep going, it's not the best. One of the things about the study that is maybe a little bit of a downside to it is that it was done in 2015. Well, in 2015, for our purposes, it's a downside, is that they have a lot of hindsight. But back in like, you know, 2000, 2001, calcium was not, it was a speculated. signal for aerobic adaptation, but it wasn't at the time like absolutely ironclad. A bunch of studies were done to make it more ironclad to see, okay, maybe calcium really does have this mechanism of action. Because when we do high intensity training, we get a lot of AMPK signaling, we're burning a lot more carbohydrates, like the oxygen throughput's really high, the proactive oxygen species is really high, the tension on the muscles is really high. And maybe it's a bunch of other stuff. So maybe that's what caused it and it wasn't the calcium. So we're going to take a little journey back into the time machine, into the... It's not a Wayback Machine, right? What was the one from... Never mind. What's the one from... Oh, the DeLorean. We're going to get to the DeLorean. Yeah. And we're going to go back to the early aughts. So the first study we're really going to dig into is called Raising Calcium in L6 Myotubes Mimics Effects of Exercise on Mitochondrial Biogenesis in Muscle. And one of the reasons I picked this is because it's a highly cited example with the lead author, Edward Ojuca. I have no idea if I'm pronouncing that correctly. He's South African and he is like a big name in the calcium signaling world. Like this, this is one of the most cited papers I saw. And after I read it, I went, wow, this is actually really well done. So I thought it would be really cool to use this as our like lead in paper. to say, yeah, look, calcium has this positive effect. So what is a myotube? A myotube, I'm glad you asked. So there are basically muscle cells that can grow in solution. Because Kyle, as you know, having been pre-med and taken a lot of bio stuff, a lot of cell types don't take well to being cultured. Like you can't just like... toss a cell line into a dish and be like, all right, just, you just be here. Like they're just going to die or they're not going to replicate. So L6 Maya tubes are their model. And one of the reasons that they wanted to use this is it's a muscle cell that does not contract. And so why Kyle, would you want your, your muscle cell model to not contract? Because you want to have it be. stable inside of your petri dish culture, whatever you've decided to grow these, or at least nurture these cells inside of. Yes, nurturing like they're pets, yes. Or children. But yeah, you were kind of correct. And it's not just that you don't want them to move around, because that would actually be really, really cool to watch these things just swim around. It's that contraction causes a lot of chemical stuff to happen. Contracting disturbs homeostasis and causes a lot of simultaneous potential aerobic adaptive signals to happen at once. So, you know, it can consume ATP, it can demand reducing equivalents and consume them like NADH, it can produce free radicals, etc, etc. All of which, even in 2002, when this was written, were suspected adaptive signals at the time. And so it's difficult to isolate just calcium as what we're looking at as a causative mechanism. So what they did was they took... the myotubes, and they bathe them in caffeine. And caffeine causes the cells- It's my morning routine, actually. I just bathe in caffeine. I know. I'm bathing caffeine myself today, too. Is this where Alpacin got their branding? And they're like, oh, what if we put the caffeine in the shampoo? What if we think all cyclists are giant myotubes? Yeah. We kind of are. So caffeine makes- these little muscle cells, proto-muscle cells, release calcium. And they did another of caffeine plus what's called dantrolene. I don't know what that is. It sounds like something from the 50s that you would get in a soda shop, I guess. And dantrolene blocks the effects of the caffeine. And so... They did five hours a day for five days, which I actually thought was really cool because that's how you just might do like a big training camp. I want to ride 25 hours this week. I've got five days to do it. Cool. Five times five hour rides, actually a pretty good training camp. So after the procedure was done, they looked at the proteins. They looked for proteins that were known to cause mitochondrial biogenesis. So they've got PGC1-alpha, nuclear respiratory factor 1 and 2, NRF1 and 2, and mitochondrial proteins also like citrate synthase and cytochrome C, and cytochrome C is part of the electron transport chain. After two days of caffeine, they didn't really see much difference in mitochondrial enzymes. But after five days, there was about a two-fold increase in most of the enzymes. So pretty good, right? Yeah. Interesting. Yeah. And after five days of caffeine, it significantly increased the expression of PGC-1, is exactly how they write it, PGC-1, not PGC-1 alpha, because it was 2002, don't forget, by about two to three-fold. But caffeine plus dantrolene blocked all of these effects, and it basically looked like the control. They also found nuclear respiratory NRF1 and 2. These are transcription factors, by the way. And so what their job is to do is to worm their way into the nucleus of your cell and start transcribing genes to express proteins to make the adaptation. that NRF1 and 2, their binding activities to DNA had increased about 1.5 fold. So that was pretty awesome. So we've got pretty, pretty good stuff going on for caffeine and calcium already. The last one is mitochondrial TFA. which is mitochondrial transcription factor A. And this is basically released from the nucleus and goes into the mitochondria to help them transcribe what few genes there are on the mitochondrial genome, which is a little circular thing in your mitochondria. Because most mitochondrial genes have migrated to the actual eukaryotic nucleus, as a lot of you probably know already. So caffeine plus dantrolene also blocks the effects of mitochondrial TFA. So overall, what do we see? They showed that exposing the muscle cells to calcium without the other adaptive signals changing the energy state, redox state, or anything replicated the gene expression as seen with exercise. Pretty cool, right? Yeah. And so then they did one more step. They said, what's the potential mechanism? Because like, does calcium just like, poke DNA and go, hey, express more of these genes, please. So they did one more experiment with caffeine plus something called KN93, which is a chemical or a protein or something that inhibits CAMK, calmodulin kinase. And this is a protein that turns the signal of there's more calcium here into actual cellular action. And so KN93 blocked expression of the mitochondrial enzymes over baseline as well, just like dantrolene did, blocking the expression of calcium. So now we see that if you block the release of calcium into the cell, you stop the adaptation. But also, if you release the calcium into the cell, but you block one of the major responsive proteins to calcium, you also stop the adaptation. two steps in this potential signal chain. So the authors conclude, and I agree with them, that the combination of the presence of calcium plus activation of CAMK and also potentially they suggest AMPK are together a powerful stimulus for mitochondrial biogenesis because they note... as we've seen in high intensity versus moderate intensity training. So I think this is worth actually delving into for just a second, right? Because in 2002, what have they seen with like moderate intensity versus high intensity training? Like moderate intensity was like two hours at 65% VO2 max. Great. Yeah. I mean, it's fine. High intensity training. Whoa, look at this signaling. Holy crap. They also just saw that they're not really comparing like for like in terms of the experiment they did here versus what you might do while training, especially if you've got a lot of time on your hands. Because otherwise, a normal way to look at moderate intensity training would be five days of five hours, right? Right, yeah. So, but also- Yeah. You know, it's after the Tabata paper, too. So, you know, people are always kind of aware of, oh, yeah, this high-intensity interval stuff. Like, it had time to, like, sink into the, I don't know, zeitgeist of training. Yeah, true. Well, also, with that stuff, you know, a lot of people are just looking at VO2 max. And one of the things that we're actually eventually going to do is we're going to separate thinking about adapt. adaptation of VO2 max versus adaptation of muscular endurance. Cause they're kind of similar, but they're also kind of different. So, you know, we might divide them up as, you know, peripheral effects like in the muscles or central effects as in, in the, like in the heart and, and circulatory system. Thank you. So anyway, You know, we've also seen now, based on the first paper that we discussed from Wastock 28, a large degree of the mitochondrial biogenesis from high-intensity training is from the calcium leak. Because a lot of the time, like, who do they do these studies on? Moderately trained individuals, like active, like college students, high school students, like young adults, people with spare time. who don't have families who can go to a study. Um, we're like, yeah, I'll, I'll, I'll do science. That sounds fun. Um, and it's very infrequently that we're looking at a study on like super highly trained people. So that's why all of this stuff has to kind of be taken in context of itself. Right. Yeah, definitely. Yeah. You can't all be, I don't know, MediCordian, get the GB Devo sprinters to be your test pool of subjects. Oh, God, if only. Oh, we should get him on the podcast. So anyway, so this paper kind of shows calcium is a good, really, really good aerobic signal for endurance. So we don't need contraction or AMP activation or any other things to happen with muscle contraction in order to make things happen, right? We have to look at another study because every time we actually go, quote unquote, up from a small model to the next model, there's potential for something to go wrong. As in wrong, as in it doesn't fit your prediction because we've now added stuff, right? And now that we've got... muscle, whole muscle fibers that can contract. And then potentially when we add the whole body, we've got hormones and all sorts of other stuff that can actually screw with what we expect. So we're going to look at one more study from 2007. We're not going to get too deep into this, but we're going to call it the whole muscle calcium experiment, because even for me, this title is an absolute mouthful. So they're looking at whole muscle and they're using rats. And one of the cool things in this experiment is that a bunch of what we're going to call secondary signals, as in the things that calcium activates, you know, previous to this experiment had, you know, they had seen that overexpression of these things and like making these things, quote unquote, always on, like always doing their thing, always led to an increase in mitochondrial biogenesis. And so they wanted to kind of dig deeper and go, okay, do we have this signal chain correct? So the part of this experiment that we're interested in is that they incubated muscles, whole muscles with caffeine for the calcium release for two, four, and six hours and looked at whether PGC1-alpha protein levels increased. So that's our main, everybody at this point probably knows our absolute main aerobic adaptive protein, All roads lead to PGC-1 alpha. Every podcast has probably beat it to death by now. And did they... Okay, so now we've got our experiment. We've got our whole muscles, caffeine exposure, two, four, six hours. Did PGC-1 alpha protein levels increase? Yes, but not during or immediately after exposure to caffeine and the elevated calcium. They only saw a significant increase. of PGC-1-alpha protein levels after six hours of incubation and then two hours of recovery time. Cool, right? So remember the last experiment on the myotubes, five days of five hours a day, and they looked at it after all that. So there seems to be a minimum duration to see an increase of PGC-1-alpha expression, right? Don't everybody freak out yet. There's something going on here because this is weird, right? Why doesn't two hours or four hours of elevated calcium do anything to increase PGC1-alpha protein expression? Kyle, you're up. Take a guess. I wonder, is it like a – it's like a – I don't know, like a homeostasis thing. Like you're, you're trying to, your body is trying to not, uh, you know, trying to maintain whatever kind of levels are currently there. And then after say six hours, it's enough exposure that you've, you've kind of like broken through the, uh, the homeostasis. Yeah. You're like, you're like half, right. That's like the second half of the right. The first half is that. PGC1-alpha is already there. It's a protein that's constitutively made. It's not like we're exercising, we've got to exercise for five hours in order to say, okay, we need to make PGC1-alpha to make aerobic adaptations. It's not like that. It's already there. And so even though it could be a couple hours between your signal and actual transcription of more PTC1 alpha, you know, experiments that, well, basically you've got it. So that way the body and the cells are ready to adapt if they need to. It's like, it's like sort of like having a, like a couple of fire extinguishers behind glass in the wall. Like that's going to cover you until the fire department gets there. Okay. So if you start exercising and you don't have any PGC-1 alpha existing, and it's such a big part of aerobic adaptation, how do we get adaptation if it's not there? We've got to exercise a lot, right? But we've seen so many experiments where people just start doing two, three hours of easy endurance-paced riding, and we see a huge increase in mitochondrial biogenesis already. So what's kind of going on is that experiments that only use expression of PGC-1 Alpha as their benchmark as to whether adaptation happens or not are actually missing something fundamental because the adaptation can happen already. And actually, when we look at PGC-1 Alpha specifically, we're actually going to look at a paper that shows that PGC-1 Alpha's action, happens before more transcription of it happens. Huh, okay. So without having to make new PGC or increased levels of PGC when alpha, because like you said, it's already there. Yeah. Your cells can just start. Yeah, and it turns out it's just adapting. Yeah, it just hangs out in the cytosol. like in the main just cell compartment. And when we start to exercise, it actually moves into the nucleus to start doing its job. And then after a couple hours, potentially there's a couple of things going on, but then your body goes, Oh, we need more of this stuff. Okay. Yeah. Let's, let's get more. This is going to be a worthwhile investment. Um, so, so that's anyway, that's a preview of another episode on PGC one alpha, but I thought that was a really, really cool thing. Um, that, maybe people should think about sometimes. And it does change a little bit of some study interpretations as to whether or not something's actually causing adaptive signaling. Because if you're just measuring expression of PGC-1 alpha, you may be getting plenty of aerobic adaptive signaling, but if you use expression of this thing, you're missing it. Right, right, right, yeah. Yeah, in a way, it's kind of how you... We've said before you store phosphocreatine ATP to cover really short, high-intensity bursts of activity before you actually kick in other metabolism. Yes, we know it's not like switches and levers where it's all of one and then all of the other, but your body wants multiple redundancies. Actually, our phosphocreatine episode was actually a good episode, I thought, about the redundancies in that system and the multiple things that it makes redundant. And even then Wonstock 40 also brought it all together about how all that entire system works. So I thought that was really cool. So let's think about calcium as a signaling molecule. Because, you know, like we kind of mentioned before, calcium doesn't really poke DNA and say, okay, you make mRNA now to make proteins. It doesn't happen that way. It's part of what's called the signal cascade. And one of the hard parts about this level of molecular bio is that there are multiple crossed signal chains and redundancies. And the complexity is unimaginable. And I remember the last time I tried to read a paper on cancer metabolism and what's going wrong with cancer metabolism. I recognize all the words, but it's so hard to put all the pieces together. It's so complicated. And this is part of the issue with all this, because if anybody starts thinking about all this stuff and go, oh, I need to hack this, remember that there's a lot of this that's still not well understood, most especially by me. And just generally, your body is kind of hard to quote-unquote hack. It's not like you're... you're reading code of the matrix and finding bugs, right? Like you're there. It's not, it's not the same. Oh God. Yeah. Yeah. You know what the ultimate biohack is training, sleeping carbs. Yeah. So anyway, so looking at the signaling, you know, now that I said we can't biohack, let's think about. Anyway, so calcium is basically what I think of as a primary signal. It activates things like CAMKs, which are secondary signals. And this is my language, by the way. This is not actual academic language. Because when we think about hormones, we've got primary messengers, secondary messengers, et cetera, et cetera. But this isn't really the same thing. Well, it kind of is, but it's not. So for instance, calcium is primary. It's an initiation event that leads to contraction. And contraction is a fairly definite signal that we are exercising or at least moving or at least spending energy. And so that's a good signal. If you were going to design a system, it'd be like, okay, if we get a signal from the nervous system to contract and the muscle doesn't contract, should we adapt to it? Probably not, right? Yeah. And so as we dig into what the adaptive signals are, We're going to find out that a lot of them, because we kind of discussed on one episode that it's not whether you're burning fats or carbs. They can change gene expression because if that's what's available, that's what's available. But it doesn't change the actual endurance capacity. And it's not a good signal for changing the endurance capacity either. So things like calcium is one of those great things. like secondary and tertiary downstream proteins had to respond directly to primary signals instead of like each other. You know, like, like, so for instance, like what if we just had one like transcription factor on DNA that had to respond to every single adaptive signal? Like it had to. It had to respond to calcium, had to respond to the change in the energy state, the ATP levels, had to respond to the change in redox demand, like the NADH demand, had to respond to reactive oxygen species, for instance. Imagine designing something that could do all of that, but as a protein. That would suck, right? Yeah, it would be... You kind of want things just to do one thing. Yeah. Yeah. And especially when we think about proteins, like they're almost like giant, like Lego or like constructor or like erector sets. They're like these mechanical things that change in their shape and the shape allows them to do certain things. And so if once we make them giant and fluffy, if we have to change the shape like of, you know, something over here responding to calcium over here and it's like on the other side of the globe, basically. It's like that change in shape isn't going to be very effective. And especially once we start adding all of the allosteric signaling type stuff that happens too. So like other places in the protein where other signals can bind and we can really aggregate pathways in one spot, man, it gets complex. I would not want a protein like that. And so as we think downstream of a... normal signal, it can be modulated by a lot of other stuff. And so for something very well studied, like a CAMK2, a signal like calcium causes a shift in its shape of the enzyme, and that changes its behavior. And that change of behavior causes downstream effects that usually lead to the cell changing its behavior or expression of genes in light of the signal. And so in our case, we're thinking about aerobic adaptation. But calcium not only has downstream effects on gene transcription through the usual suspects like CAMK and CREV, which is cyclic AMP response element binding protein. So obviously it's going to respond to cyclic AMP, epinephrine, blah, blah, blah. Calcium has other cool effects in that it can actually modulate epigenetics. Interesting. Did you see that coming? No. That's cool, though. It's very cool. So, Kyle, do you want to explain epigenetics real quick? Yeah, epigenetics are pieces or parts of your DNA that are not expressed all of the time, but can be turned on and off due to exterior... We'll see. stimuli or your environment or things that you're exposed to. Yeah. Which is cool because it's like you can – it's going to sound bad. It's not like things you can unlock by experiencing new things, but it kind of is because it is something that – this is also something you could potentially test for. Like if you get a DNA test done or something like that and they – print out your genome. They could look for things that would be more epigenetics than like genetics, whereas genetics normally would be like, oh, common things that we think of like hair color, eye color, height, stuff like that. Whereas epigenetics would be, oh, because you experienced this external stressor, now your body has decided to do X, Y, and Z. Yeah, it's sort of like another layer of regulation on gene expression. And so what's actually happening in epigenetics is we have the DNA is wrapped around what are called histones. And it's literally kind of like curling hair on a curling iron. Or like a hose around a hose wrapper thing. It gets wrapped up, although maybe the hose is a bad way to think about it. But it's just wrapped up. And epigenetics... is a way of modifying whether these histones cluster together or spread apart. And calcium is one of those things that can make certain elements of these histones spread apart and make it actually easier for transcription factors and other goodies that have to get in there to actually express these genes. It makes it easier for them to get there, or even possible to get there at all. And so when we're thinking about... epigenetics, like this is one of those other layers that's really difficult to measure, um, and, and really do anything about. So another reason is dumb to do this podcast, but I think it's really cool anyway. Um, so like, um, so Uh, the, the, the signal chain is actually too complex to even explain. Cause like even my eyes would gloss over if I tried to explain it, but basically what happens is calcium says to a thing, Hey, this is cool. And there's a thing that usually makes that thing disappear. And it goes, no, okay, you're going to stay here this time. We're going to do this thing. And then we get adaptation. I know your eyes glossed over anyway. So how do we actually use? all of this. And I've said this in many podcasts before, but I'm going to repeat it until hopefully it becomes part of the modern Zika training. Well, if I have any influence on it at all, which questionable also, but the maintenance of homeostasis is what aerobic adaptations are all about. And so you have to perform work, you have to make the cell contract, and that disturbs homeostasis. And aerobic adaptations are geared towards the maintenance of that in the cells. So like energy state, ATP's ability to do work. Refer to Wattstock 40, 10-minute tips number six, et cetera, et cetera. And that all means that glycogen stores are better maintained close to or fully at resting levels as we perform submaximal work, right? And that's what we're trying to do. We're trying to make better endurance in our muscles. But if we try to big brain this to improve our endurance, Kyle, you had an idea before. What was your idea about how to big brain the calcium thing? Was it some sort of infusion? Yeah, or could you have higher levels of calcium intake right before exercise just to get a little extra stimulus out of it or maintain higher levels of calcium after exercise? Yes. Drinking the extra gallon of milk. Go mad. Where's rip it to? Well, first you would have to consume it. Then it would have to get into your bloodstream. Then it would have to get into your muscle cells. And then you would have to contract your muscle cells. So you still don't escape the work. But so I'm sure a lot of people are thinking. cadence, right? So if, if contraction releases calcium, can I pedal at a higher cadence, which would make me like it'd be exposed to more calcium potentially. Um, this actually doesn't work because the contraction durations are shorter. So the overall time contracted is the same, which is not a very good strategy. And also peddling that fast game. Yeah, pedaling like at 110 RPM for a couple hours is really difficult. But, you know, if you lower cadence, it also doesn't hurt the signal, which is one of many anyway, right? Which is why, for a lot of things, pedaling at self-selected cadence is fine. Yeah, you tend to end up a little extra fatigued if you go a little lower, a little higher than your normal way to go. And also, it's like a mental load. You don't want to have to think about, I have to maintain this exact cadence while you're out on a five-hour ride that should be enjoyable. Probably doesn't sound like a good use of time, or mental time anyway. But if you're thinking, oh, maybe I want to get into some larger motor units, right? So I'm going to lower the cadence. This would get into some bigger motor units, but there's actually some evidence in the literature that low cadence endurance riding probably doesn't matter that much. I mean, the evidence is not absolutely ironclad, but also in practice, at least in my practice, it doesn't really seem to matter. I've got some riders who have gone from really good local elites to... winning UCI points, um, at big races. And I don't think we've ever done a low cadence effort ever. So, um, it doesn't, it doesn't really seem to matter as, especially if you can, um, train a lot, if you're looking for marginal gains, you're a little time crunched, maybe, I mean, as long as it doesn't hurt you, sure. Try it, see what happens. Um, no promises. So, um, so like, um, like a Juca had said, um, you know, he said that Calcium plus other signals is probably a very potent signal for adaptation. And, you know, he's probably right. But, you know, if we looked at a lot of the things that would positively modulate PGC1-alpha for adaptation in terms of transcribing things like mitochondrial biogenesis, making more PGC1-alpha, you know, we can see crazy stuff. Thyroid hormones, free radicals, AMPK, MAPK. Cam K, calcium, like again, sirtutins, like the list goes on. You can Google it, like PGC-1 Alpha, go to, you know, read a paper. You're going to see a lot of stuff. All of this is stuff that happens when you ride and train as you would anyway. You're not going to get much. You're probably going to drive yourself crazy by trying to adjust for this kind of thing. But, well, let's save that for – I have one more thought. We'll save that for just a minute. But what's one more way we could big brain this, Kyle? What is a way to increase the duration of calcium in a contraction for quite some time? Blood flow restriction. No. So fast. I felt like I said that like Alex Trebek would. No, isometrics. Ah, okay. Right? So if you hold the muscle contracted, but how long can you do an isometric for? Like five minutes? Where's Joel Seedman? Don't even, don't speak that name. So like, yeah, how long can you hold the bottom of a lunge? Until your legs shake, three minutes, five minutes, maybe the best in the world, like 10 minutes, a little more. I don't know. I think in college we had like team fitness testing, I remember, for swimming. And I think I did a wall sit for like 15 minutes. Ew. Well, like a wall sit's a little different. I feel like the tension isn't quite as high. Like I've done isometrics like bottom of a lunge. My quads shook quite hard after just a couple minutes. Yeah, not a good idea. Also, there's a lot of fatigue associated with that kind of thing. I mean, I remember the first time I ever tried an isometric like that. My quads were tired for like a day or two after that. So not a great way to go. Probably better use of your energy to spend that time riding. And it's less fatiguing. Yeah, imagine that. So what can we realistically do with this information? So cellular calcium levels are not something that we can realistically modulate with in terms of duration and intensity. Like we can't really cause sarcoplasma reticulum leak during normal training. Well, if you can, while you're probably doing something really dumb, don't do that. Because we can modulate power, we can modulate heart rate, we can't really modulate how much calcium we send into the cell. But we can modulate how long we send it to the cell. How long are we riding for, right? Because it's either on or off in a muscle until we get leak. And this is what we can realistically control in terms of an adaptive signal is just riding. Because we don't have to freak out. Again, the last paper showed you you need six hours of calcium to increase PTC1 alpha expression. It's already there. It's either all occupied and it's like, hey, PTC1 alpha, can you do some more transcription? It's like, I'm busy. Okay, cool. We'll get some more. Either that or it's like getting beat up with entropy. You need more. Who knows? I don't. So in practice, The other thing I notice is that it seems like there's an absolute direct relationship between the time spent riding at a low intensity, it doesn't really matter what intensity, and your endurance, fatigue, resistance, durability, et cetera, whatever you want to define it as or call it. Base training. Yeah, base training. Yeah, positive correlation in terms of the effect you get and how much time you ride. Riding more at any pace. Any pace at all is going to increase the calcium signaling in a direct and fairly dose-dependent way. Kyle, you might call this a first-order effect? Sure. Yeah. Yeah, yeah. I think this is like that meme where I said, you know, volume is the driver for aerobic adaptation. Oh, yeah. And it was the person whispering into the ear and the goosebumps. Is that the one? Yeah. Yeah, yeah. Yeah, it gives me goosebumps every time. But one of the other potential things that's happening is the longer we ride, we may be modulating the epigenetics by having calcium in the muscle longer. And so just a speculation, I have no idea if it really works like this. Somebody smart will figure it out at some point, and then we will talk about it. If you really want a signal for aerobic endurance, the simple and easy answer is to ride as much as you reasonably can, and then recover, don't forget, and ride at a pace that's easily sustainable. Because one of the things that this shows is that you don't get more out of more watts. You mean the one watt below zone three is not better? Yeah, maybe not the right way to approach an endurance ride. I mean, yeah. Sorry, go ahead. No, no. I just think also with endurance rides, with everything else, you want to be able to go somewhere too, right? Which is why you say at a pace that is mildly challenging but sustainable. Because if you did five hours this week, you want to do six hours next week or a little bit more. You don't want to just be tapped out. pinned it at five hours, couldn't possibly imagine doing any more, you know? Yeah, no. And that's the kind of thing where the fatigue is a lot more than the signal that you give the muscle. And that's why I've always said, you know, in terms of like pacing endurance rides, you just want to ride at a pace that for a lot of people feels suspiciously easy. It's like, oh, I don't have to push. I'm not like dreaming of food and I love that. Well, yeah, always dreaming of food. It's like you're not – it's not a vision quest to get home. Everyone's been on one of those rides. Yeah, just stop. Hopefully you bring some money or whatever. Yeah, just stop, get some water, get some food. You're going to be fine. So in terms of calcium signaling anyway, what these studies show is that you may – it's all speculation, of course. I'm not going to be one of those. The science says. No, it shows that you may get more of this particular signaling out of increasing the duration of your longest ride. And I usually say it doesn't matter if you do two two-hour rides or one four-hour ride. In terms of this alone, it may matter more if you do a four-hour ride than two two-hour rides. Just this. In other ways, it doesn't matter. Because you still get the same amount of contractions. But as we saw with the expression increase in PGC-1 Alpha only happening after six hours or five days of five hours, there may be something to that. So who knows? It's certainly worth trying. But don't go rearranging your life and causing a lot more stress because honestly, if you increase the life stress to get a longer long ride in, it's probably going to be a wash or actually it's going to make everything worse. And especially if you don't eat enough on your long ride, you can also screw yourself in other ways. So that's one of the ways to think about all this. So here's my other thought also on the motor unit thing. For middle intensity, so between LT1, like the top of your endurance range, and FTP. So for that. In Seiler's three-zone model, the Polaris model, this is zone two. I don't know. How many ways can we have zone two these days? So by doing intervals, you get to use more motor units, but you're also now adding a lot of other signaling, right? This is why I call it spicy endurance because it's the same signals, but the rate is higher and you're adding a couple more. Like you're adding in like AMPK when you do this kind of stuff. And as you do this, you are now getting into where you're like stacking signals, right? And this is something that you would do training normally. You would normally do a long endurance ride. You would do FTP efforts. You would do blah, blah, blah. Like you don't have to absolutely go nuts trying to think, okay, if I do low cadence endurance and then I do FTP, like just, just train normally. It's probably going to be fine unless you have a specific need. Like for a race or a weakness, something like that, it's probably going to be fine. Massive gear 500s. I'm thinking like 150 gear inches. 500s like meters or kilometers or like 500 kilometers? Meters, just 500 meters. Okay. Yeah. I would think that the duration is pretty low, but if you do enough of them. God, can you imagine? I mean, you might as well just sit in the gym and lift something really heavy for like just super set sets of like 20. And then wait an hour that do more and then wait an hour. That sounds terrible. I would rather just ride a bike. It's probably less fatiguing. It's probably better, way better. Look at that specificity. Cool, right? So Ojuca, I kind of hope I'm pronouncing that right, speculated that there, well, it turns out that there's some definite evidence to corroborate his speculation that adding in other molecular pathways like MPK signaling to your calcium signaling may have a positive additive effect. But all that just goes to say that This might be one of the reasons that doing a lot of volume along with pretty much anything else, except really besides strength training, means that that one other thing that you're working on tends to improve a lot more. Whether it's VO2 max or TTE or repeated efforts or anything like that, they all seem to get better if you are riding more. And it may be part of the fact of getting into larger motor units like this or the signals stacking or who knows. It just seems to work really well. So when we really dig into all of this, like we have, the actual adaptive signals that we see and what they tell us, all of this supports the training philosophy that I stole straight up from Dean Golich. I stole it fair and square that no one type of training is a silver bullet. Miracle interval. God, I'm never tired of that joke. I know. Oh, man. It's almost funny every time, too, except it's like I know people have tried them. Yeah. So anyway, so where are we at with our summary on this before we get to listen to questions? Yeah. So it's interesting and in a much more academic sense that calcium is an important signaler in endurance. A lot of times people probably think, whoa. Maybe they think of calcium as being an electrolyte that might be in some maybe slightly more fancy boutique sports drink, like most of them are just sodium and potassium. But then also, if you're thinking, oh, like you said, if I'm going to hack this, I'm going to somehow apply this newly found calcium knowledge to my training, and that's going to make many percent difference. It unfortunately doesn't work that way. But it maybe does, you know, peel back the curtain a little bit on why things work the way they work. Or, like you said, why volume kind of seems to be the driver, primary driver for aerobic adaptations. Yeah. Yeah, no, really. And there's a paper that we're going to look at eventually that is looking at, you know, actually there's a couple. that are looking at a couple things about volume that really show that, you know, number one, like easier is probably better. And, you know, and the intensity doesn't really matter. And that the kind of total volume just matters quite a bit. So we're going to get into those. And I'm really looking forward to those. But for now, why don't we get to some listener questions? So this is actually a really tough one to add. ask, uh, our listeners because who the hell is like really thought about, Oh, I'm going to work on my calcium signaling today. Um, so, so I kind of posited this as, um, uh, you know, questions about aerobic adaptation, signaling and endurance rights. So does that seem like a decent kind of question for all this? Yeah, I think so. All right. Oh, an explanation of why anaerobic training doesn't cancel out aerobic training and vice versa. This is one of the big reasons why. Because, so like aerobic training, contractions are contractions, right? Like if we're just thinking about calcium signaling, calcium being one of the big signals, contractions are contractions. Like you're not going to stop yourself from... calcium making your muscle cell contract. If you do a lot, actually, if you do so much anaerobic training, you can barely move your muscles. Okay, yeah, you've screwed up for sure. I believe that's called a kilo. Yes, that is called the kilo. Kyle, are you alive yet from that kilo that you did the other day? Yeah, yeah, yeah. I'm alive. Oh, you've got a kilo and a sprint tournament coming up next week, don't you? Yeah, they put the kilo the same morning as a Kieran tournament, which is an interesting choice. Oh, the Karen term. Yeah. Well, Kyle's funeral will be held on the following Wednesday. You're like, oh, man, just going to. I mean, they may as well. I think it'll be interesting, to say the least. It'll be interesting. Yeah, I'm looking forward to it. I'll have pictures of you lying in the grass dead and people pouring water on you. Okay, next question is, I believe because of zone two hype, most folks overthink the endurance rides these days. Yes, I think that is partly correct, but also I think a lot of it still fundamentally comes down to the Coggin zones of like percentage of FTP. And I'll say it again that in my experience, it doesn't matter how easy you ride really. I would say a lower limit is probably about 30 to 40% of LT1. LT1 can be as low as like 50% of FTP. So that is quite a low percentage of FTP indeed. Like maybe 25% is the low limit for that. Maybe 20%. Who knows? It doesn't seem like the lower limit really exists, but the upper limit exists because of the fatigue generated. But especially if we're going to think about calcium signaling, it's absolutely irrelevant. Yeah. And in practice, it seems to be absolutely irrelevant as well. My high volume people all doesn't matter how hard they ride as long as they don't ride too hard. Some of them still ride too hard. We're working on that. But most of them are just nailing it. So yeah. If a little over LT1, sorry, this is the next question. If a little over LT1, like 15 watts, if enough time is spent there, will it eventually equal threshold stimulus? No, not really, but also yes. So for somebody who's fairly well trained with good endurance, good TTE, you can ride over LT1 for hours and hours and hours and hours. I've trained people where they can ride for six to eight hours over LT1, like continuously. And it's like there's not that much heart rate decoupling. but the fatigue is there. And that's the biggest clue that they're over that. I wish there were an easier way to detect it, but we really can't see it as with all the tools that we have so far. So yeah. Yeah. And the adaptation, it's basically the same as if you do 15 watts over or 15 watts under or 15 watts over and 30 watts under. Here's the difference. 30 watts under. You can ride a lot longer. Guess how much more calcium signaling you get? Kind of a lot. Yeah, it's proportional to time. Like you said. It's more proportional to time. And if you think about that 50 watts, how much more torque do you actually put out for that 50 extra watts per pedal stroke? Not a ton? Like a couple newtons? Yeah, not a lot. It's, it's, and especially if you can generate like, I don't know, a thousand newtons of force maximally, or most people can do more. Um, yeah, you're really not getting into, and then of course it's a question of motor unit recruitment and are you standing or sitting or whatever? So it's too complicated. Don't worry about it. Just ride, ride at a sustainable pace. Uh, we went over that. Uh, yes. Um, well, yeah, the downside of pushing hard on endurance rides is recovery time or actual adaptations. Uh, it's actually, you get, yeah. So like we just said, um, you will get less adaptations because you are fatiguing faster and then you get more, or you need more recovery time. Um, and then it also screws up with your harder intervals too. And it could potentially screw up with your races as well. And that can really throw people for a loop because then they think, oh, I need harder training. It's not the right approach. Um, how much does stopping matter or how much does not stopping matter? Um, one minute, five, 10 minutes doesn't matter. Um, I, well, at least in practice, it doesn't really matter. Um, the time spent riding is the time spent riding and I don't see much difference between like, you know, a five minute stop and an hour stop. Actually, with an hour stop, you can probably eat quite a lot and have a couple of coffees and you can ride for a lot longer after you've had a lot of food and motivation. It might take you a little bit to warm up again, but yeah, it's totally fine. I never, ever, ever tell people that they shouldn't stop. Yeah, it's silly to think like you ruined it, right? We played this game before, like you can do reductionist like, well, okay, so if an... And how long of a stop is an acceptable one? Yeah, just stop, get your food. It's fine. I get wanting to not cool down so much because I'm a person, like when I was doing long rides, I dreaded that first 20, 30 minutes of getting back on the bike because I would feel horrible. Then I would be smashing everybody on the way back because I ate more than they did. I had better legs at that point. Man, I was an early adopter of eat a lot of carbs on the bike. Let's see. What makes too easy too easy from a signaling perspective? So actually, let's take this from another way. Where's the border between riding endurance too easy and a recovery ride? Kyle, what are your thoughts here? I'd be curious. Ooh, I don't know. Like, if it's a recovery ride, like, you want to feel better afterward. Like, if you're a little sore, you're a little tired, like, you go out for a recovery ride, and by the end you're like, oh, I feel better. And for an endurance ride, you still kind of want to feel like you did work. Like, it's not soul-crushing work. Like, you know. five hours of high tempo or something. Um, yeah, I was either some, there's somewhere in there where like after a, like a, uh, a recovery ride, it's, it's very much a, you know, refreshing experience, not a, not a work, a working experience. Yeah. I like to think about it. Like what's the minimum you need to get what you want. And for a recovery ride, you barely need to brush the pedals. You basically need to loosen up your muscles and get a little bit of blood flow going. It may increase nutrient exchange. Who knows? Blood flow is very restricted to the muscles because oxygen is corrosive, as we said. Literally, oxidation is rust, right? So you don't want to rust your muscles while they're not being active. But yeah, it doesn't take much to do a good recovery ride and feel good when you're done. If you want to look at it in terms of TSS, 10, 20. Yeah, like as simple, as easy as just like riding your bike to the store easy and coming back with groceries. Yeah. Yeah, like taking a walk is also a good recovery activity. You don't have to be on a bike. It's nice. It's fun. And if you're somebody who also does their recovery rides too hard, take a walk. Nice and easy. Bring your mother. Hit the bricks. Yeah, so let's see. I've said before that high FTP, I can expect with X volume. So basically, your volume kind of determines your FTP. We're going to talk about that when we look at more central adaptations. Um, but that is a good question that, and, uh, it's on the list. We will be getting there for sure. Is it worth looking at your heart rate during long rides? Personally, it stresses me out. Um, so stop that. Yeah. Yeah. Yeah. I, I personally don't think it's, it's worth looking at in some ways because I know a lot of people like to keep in their periphery in terms of like, oh, I'm cruising at this power or whatever, or this. pace and my heart rate's a little high, but it's hot out. So maybe I should expect that. Okay. Or like, maybe I'm getting sick. My heart rate's a little high. Okay. But yeah, for the most part, no. Cause I've heard a lot of people talk about heart rate. Siler, did Siler talk about this? Maybe he's the reference that people have mentioned where he says that the heart rate is going to be indicative of the internal strain of the workload. And I don't necessarily agree with that because it, It indicates dehydration. Okay, sure, that's higher internal strain. But it also can indicate increasing motor unit recruitment. Is that necessarily higher strain? I'm not entirely sure it is. Maybe the muscles are not having that good a time. What's strain? Yeah, but they need the work anyway. Yeah, so how do we define the strain? I mean, I've got some clients who can ride for hours and hours and hours without the heart rate decoupling. Um, and yet with all that kilojoules burned, uh, they sure have the need for some recovery. So they get the recovery. It doesn't mean that the, you know, whatever strain hasn't increased over the ride. So, um, so yeah, it's, it's worth looking at, especially actually if you are at altitude or in like a new hot environment or humid or something like that, just keep it in check is a good approach, I think. Let's see. Endurance added to the end of a workout versus the same length endurance ride any better? Is it different? Well, in terms of calcium signaling that we're talking about here, it's pretty much the same. If you add some intervals or something, it's going to increase the motor equipment, obviously. But it doesn't really matter that much in terms of all this stuff. it doesn't change the adaptive signaling. Like it can, if actually, if you bonk, then you can't really ride that hard. But yeah, no, it's like, here's one of the things I advise people of, especially when I consult with them, is a lot of people ask me, should I, can I do my intervals on a longer ride? Or should I save them for the shorter rides? And the answer is, it doesn't really matter. Like you do the intervals in the days it makes sense to you in terms of time and fatigue, and you could do the long rides or the shorter rides as your schedule allows. You can mix and match. It's not critical. Like you can do a set of like sprints or VO2s like on a long ride or a short ride. It's basically irrelevant. Is there potentially some benefit to do some intervals and then? Ride easy for a while? Potentially, yeah. But that's like one of those very small marginal gains that we will potentially be looking at. Besides RPE, what data and metrics are useful for tracking effort and adaptation during and post-ride? Time. Time, intervals, it's pretty simple. There's no big branding, any of that kind of stuff. Keep it simple. Um, let's see. Uh, what is the minimum length endurance ride where benefits are better than just a day off like 30 minutes? Um, that's an interesting question. Um, like, like as in, do I, do I, I guess it's like, do I at least have to do two hours or should I just take the day off is what the question is. 

Yeah, I guess so. Or like, what is, if you can't, if you don't have as much, if you only have 30 minutes, like what, what do you do? I don't know. Okay. Well, somebody I consulted with a while ago was doing like an hour of zone two at pretty much every chance he got. And actually one of the downsides of just doing an hour. is that you can actually do it too hard by kind of a lot. Because if you're riding tempo, it could take you some time before you really go, oh, this is a little spicy. I better pull it back. So that's a downside of a shorter endurance ride. I think in terms of signaling, I really just think about what are your longest rides is one of the ways I think about it. And also, what's your total volume in a week? But still, Just don't overdo the recovery days is probably the better way to think about it. If you're going to recover, recover. If you're going to do a workout, what's the purpose of the workout? And don't skip recovery days, especially. Yeah, I like that. Recovery days are for recovery. Yeah, because like I saw, if you do an hour of zone two pretty much every day, instead of doing a recovery day, as you should a couple times a week, the fatigue adds up, especially if it's actually tempo and like overall T1. Let's see. Just riding around still improves the entire PDC, the entire power curve. Well. My friend, you are one lucky person. Congratulations. Yeah. Noob gains for life, man. Noob gains for life. FTP is at five watts per kilo. Everybody listening, you may now boo him. I'm jealous of your functional cardiovascular system. Yeah. What to infer about my physiology? Well, here's one of those things where not everybody's like this and you're very lucky to be like that. Like Coach Katie. is like this, where if she just rides a lot and does a handful of intervals, not even, it'll increase her FTP. If she just rides like a big volume week, her FTP will go up. And she's been riding for years. So you're like that. You are a genetic freak in the good way, and you are very lucky. So enjoy that. A lot of people have to do a lot of very hard work in order to get that to happen. So if ever you start coaching people, don't expect them to respond the same way is also probably a very good piece of advice. And if you're listening and you actually do respond that same way, you are a very rare breed and a lot of people are jealous, including me. Last question. Endurance after zone four, a shortcut to training big boy motor units? Um, no, it is actually not. You are still recruiting just a few small motor units, especially if you're pretty well trained. Uh, you're not going to get into big motor. Like when's the last time you did an endurance ride where you felt like you were pedaling as hard as you possibly can? Um, I would say, so back when I lived in Rhode Island, getting up, up college Hill, there's a very. quite a steep hill at the end. So you come back from an endurance ride and then you have to like slam it up this like 10% hill to get up back up to where you live. Okay. Not really where I was going with that, but I appreciate the anecdote. Nothing like throwing on a 45 second test at the end of an endurance ride. God. Yeah. And I thought my like 15 second up, up, up my hill in Boston when I left in Dorchester, I thought that was, I thought that was. hard, but okay. Yeah. You got me beat with that one. I know that hill. Um, no, um, here's the thing. It's like, like you don't really get to recruit motor units that are that much bigger, uh, by doing that stuff. So it's, it's, it's just better to, um, to do intervals. I mean, that's it. And we've talked about on the podcast before where, you know, doing over-unders or like intermittent efforts to longer durations. that's a good way to get into the bigger motor unit. So if you're going to do FTP stuff and you want to get into bigger motor units, just do FTP work or do over-unders or do 15-15s for 3x20 or something like that. And don't do them all out. Do them to an FTP-type pace. And that's a better way to do it than to kind of big-brain this kind of stuff. Because if you just do a bunch of... threshold intervals, and then you ride endurance, you are creating less force riding the endurance. So, I mean, yeah, there's going to be some increased motor unit recruitment, potentially. It's hard to say, can't guarantee it, likely, sure. But it's better, you will get better motor unit recruitment if you actually just do regular intervals. For a lot of people, that's really the only motor unit recruitment, like big braining that you actually need. It doesn't really have to be that complicated. Yeah, so how are we doing? That's our last question. Yeah, I think it's good. I mean, I know people are probably like, oh, this isn't one of the episodes that has the most actionable training, direct training advice because you're like, oh, how do I manipulate my calcium levels? Oh, wait, there isn't a way. it is kind of like, you know, slowly layer by layer trying to point people toward the extra, the extra stuff that's underneath the hood. So that's kind of nice. Yeah. I mean, it's like somebody sent me a Reddit thread. I haven't been on Arvelo in a long time, but somebody sent me a Reddit thread that pretty much said, what was the title? It was like, the more I listened to the empirical cycling podcast, the more I realized I just need to ride more, I think was the title. And, uh, yeah, it's, it's the nicest thing anyone's ever done. That's very true. Oh man. Um, yes. So that's, that's very true. Well, here's the other thing is that by, by talking about, even if it's not as actionable, because I know a lot of people are very time crunched, um, even if it's not as actionable as you would like it to be. And when we talk about other signaling pathways, I'm also going to chide people on it not being as actionable as you would like it to be. You will also, I hope, have a weapon against the bullshit out there too. That's a good point, yeah. Where you realize, oh, this isn't on the list. Well, first of all, you should look it up, whether there's evidence to support that. And if you're in doubt, ask me, although you probably know my opinion if you've listened to enough podcast episodes. So I think that's another purpose here is, you know, kind of like the biochem episodes. I know that a lot of them were kind of like a boring lecture series, but at the same time, I thought it was important for people to kind of get even a general picture of how the metabolism worked because I wanted to build on that. And if I spent... 30 minutes explaining all that kind of stuff before you get to the main point. I've lost you already. And I know I've lost a lot of people right now already. I'm so sorry. We're an hour 20, hour 25. Yeah, let's bring this in for a landing. So yeah, Kyle, so what do we have for our big conclusions, takeaways that are really actionable is potentially make your long ride longer. Just think about time. The intensity doesn't really matter, especially for the calcium, which is a big aerobic signal. Do regular intervals. Do all the basic stuff. Right? Yeah. Keep it simple. Keep it simple. Oh, okay. I guess we're done. Don't try to big brain it. Yeah. All right. So everybody, thank you so much for listening. Again, if you're new here and you like what you're hearing, please subscribe to the podcast. And if you are an all-time listener, we really appreciate having you with us. If you've reached out for coaching, we really appreciate that. If you have donated to the podcast, empiricalcycling.com slash donate, we really appreciate all of those donations. We appreciate the sharing of the podcast. We appreciate that Reddit thread. So shout out to whoever put that up. You are absolutely right. And if you don't have that much time, I'm so sorry, but, you know, reach out for coaching. We can help you make the most of the time that you have or reach out for a consultation. And we can do one of those. If you have any questions or comments, please shoot me an email. Or if you want to check us out on Instagram for the weekend AMAs or for podcast questions, please follow me at Empirical Cycling. And with that, I guess we will see you in the next episode. Bye. Yeah. Thanks, everyone.