In this episode of the Flex Diet Podcast, I’m joined by my good friend Dr. Eric Trexler, exercise scientist, educator, and Director of Education at Stronger by Science, for a wide-ranging, no-BS conversation on what physiology actually looks like in the real world. We dig into beetroot juice, nitric oxide, and “pump” supplements, why the blood-flow story is usually oversold, and why neuromuscular function and calcium handling may matter far more than chasing a swollen muscle. We also talk about why most supplement mechanisms sound great on paper… and quietly fall apart once you look at healthy humans who already function pretty well. From there, the conversation expands into human variability, elite athletic outliers, and why normal distributions actually guarantee that “freaks” exist — whether people are comfortable admitting it or not. We also unpack NEAT, energy expenditure, and why exercise doesn’t scale linearly for fat loss, including how the body aggressively manages its energy budget when stress or activity gets too high. If you care about performance, body composition, or just understanding how the human system really works, this episode will recalibrate a lot of assumptions.
In this episode of the Flex Diet Podcast, I’m joined by my good friend Dr. Eric Trexler, exercise scientist, educator, and Director of Education at Stronger by Science, for a wide-ranging, no-BS conversation on what physiology actually looks like in the real world.
We dig into beetroot juice, nitric oxide, and “pump” supplements, why the blood-flow story is usually oversold, and why neuromuscular function and calcium handling may matter far more than chasing a swollen muscle. We also talk about why most supplement mechanisms sound great on paper… and quietly fall apart once you look at healthy humans who already function pretty well.
From there, the conversation expands into human variability, elite athletic outliers, and why normal distributions actually guarantee that “freaks” exist — whether people are comfortable admitting it or not. We also unpack NEAT, energy expenditure, and why exercise doesn’t scale linearly for fat loss, including how the body aggressively manages its energy budget when stress or activity gets too high.
If you care about performance, body composition, or just understanding how the human system really works, this episode will recalibrate a lot of assumptions.
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Speaker: [00:00:00] Welcome back to the Flex Diet Podcast. I'm your host, Dr. Mike G. Nelson. On this podcast, we talk about all things to increase muscle, improve body composition, and improve performance all within a flexible framework without destroying your health. Today on the podcast, my good buddy, Dr. Eric Drexler, and we're talking about a wide range of stuff, everything from.
Uh, beet root and nitrate research, uh, pump supplements, elite athletics and physiologic variability. The role of genetics in athletic performance. Even a little bit on the debate about steroids versus air quotes, natural, uh, bodybuilding, the use of peds, uh, blood flow, and even talk a little bit towards the end about the role of neat non-exercise activity thermogenesis.
In weight management. So I'm super stoked about this [00:01:00] episode. I always love talking to Dr. Drexler because he is got such a wide range in the background, both from his academic side and, you know, working with actual clients, doing science, writing and doing a lot of, you know, training and work on himself.
I first met Dr. Drexler when he was just started his graduate program. I think, uh, we met at a conference talking about metabolic flexibility because some of the stuff he was, uh, looking at kind of worked on that area too. So, Dr. Eric Drexler is an exercise science and educator specializing in resistance training, hypertrophy, and evidence-based nutrition for strength and physique athletes.
He is currently the Director of Education at Stronger by Science and a research collaborator with a Duke Molecular Physiologic Institute. Uh, his work there focuses on muscle physiology, training and adaptation and performance outcomes. [00:02:00] And like I said, what I really like about him is he is able to translate the complex research into things that we can understand and apply.
Um, but at the same point, he understands the. Background and how the complexities, uh, do translate. So I think you'll really enjoy this podcast here, and this episode is supported by a few companies I already use and recommend. Uh, so check them out in the links or on the website or wherever you see it below.
Uh, no, these are affiliate links, so if you do purchase from them, I do make a few shackles and it does go to help support the show. So number one is element. I was drinking the raspberry form today, and this is something I still use many years later, like literally every day. Um, because it, one, it works really well.
And two, the other part I've noticed is I don't really get that [00:03:00] tired of the flavoring. I do kind of rotate, like lately I've been rotating between the raspberry and the lemonade. Now the new lemon one is really good. And I still enjoy it many, many years later. So if you're looking for hydration support, check them out.
Either one is the shift wave device. This is a way of shifting your nervous system. This can be both for upregulation or downregulation slash recovery. Uh, as of this recording, I used it this morning for 30 minutes more on. The muscle side of recovery, since I am kind of beat up from training, but in a good way, like mostly doms in the right muscles, uh, joints are all feeling pretty good.
So I did a 30 minute session there to help with that. And a couple days ago, uh, played more with the upregulation portion of it, which is just nine minutes, uh, before the lifting session here. And it worked great. So if you're looking for a way to. [00:04:00] Uh, change your state of your nervous system. Uh, I find it's especially really good for promoting recovery.
IE getting back to baseline faster and downregulation. Check out my friends over there at Shift, wave. And last but not least, my newsletter. If you're interested in a lot more information along these lines, sign up to the newsletter below. I send most of my content. Probably 80, 90% of my content goes out to the newsletter only.
I just sent one the other day about the use of GLP ones and increases in heart rate, uh, which is from the literature and frankly, I don't see many people talking about it. So it is a little bit on the geeky side for sure, but we try to make them as interesting, uh, as possible. And I just have a ton of fun writing for that.
So you can get onto the Insider newsletter for free. Down below. So thank you so much for listening to the podcast and enjoy this episode here with my buddy, Dr. Eric [00:05:00] Drexler.
Dr Mike T Nelson: Welcome to the program Dr. Drexler, how are you doing?
Dr Eric Trexler: I am doing great. How are you?
Dr Mike T Nelson: Good, good. Awesome to have you on here.
It's I think it's been a little while since I'm trying to think the last time I talked to you in person, was it the. Fitness summit, I think, or was it experimental biology? I know it was like well before that, I think, but I think that might be the last time I saw you in person, maybe.
Dr Eric Trexler: Yeah. It must have been that.
And I, I don't think I've ever been to experimental biology, so you may have, maybe it
Dr Mike T Nelson: was a different one.
Dr Eric Trexler: You may have bumped into my doppelganger, which would be a frightening concept. I'm sure we've seen each other at maybe some ISSN stuff maybe.
Dr Mike T Nelson: Yeah. Ssn we have for sure.
Dr Eric Trexler: Yeah. Yeah. But yeah, it's been years for sure, either way.
Dr Mike T Nelson: Yeah. And you're over at Duke now doing research and teaching?
Dr Eric Trexler: That is correct. Yeah.
Dr Mike T Nelson: And you're still doing all the stuff with the wonderful guys and gals, over at Mass there.
Dr Eric Trexler: That is true.
Dr Mike T Nelson: Awesome. And the [00:06:00] first topic I wanted to talk a little bit about is, I know you did your PhD work in bee Root, not to bring up old memories of PhD work.
I still feel like I'm recovering from a mild form of PTSD from doing mine, but, it seems like it's becoming a little bit more popular again. And I, it just feels like to me, and I haven't done research in this area as a more, an outsider that I don't know if we, it seems like we've forgotten all the basic mechanisms and simple stuff like standardization and what is the goal.
I just see the dosage going down, not up, and I'm confused on that. So maybe if you can just start us off of what was the infatuation with Beru? Why did you start studying it and just the, a background to fill people in if they're not familiar with the mechanisms and how it's proposed to, to work.
Dr Eric Trexler: Yeah, for sure. When I started grad school, I had two parallel lines of research. One was on [00:07:00] metabolic adaptation and energy expenditure adjustments. The other was in supplementation. And I got into grad school. I was really into supplements and. Of course, if you're really into supplements and you lift, then pre-workout supplements are, where a lot of people Of course, yeah.
It's the most interesting thing. 'cause you say, what can I take now to help me now? Right.
Dr Mike T Nelson: Yeah. It's
Dr Eric Trexler: Like always of interest to a supplement user. So early in my, actually my master's thesis was on both caffeine and creatine, which of course are staples and pre-workouts. Around the same timeframe, I published a big paper in the Is SSNs Journal about beta-alanine.
Mm-hmm. And so for my dissertation topic, I was like, Hey, let's hit for the cycle. And so my dissertation topic was specifically on both citruline and beet root juice as a source of dietary nitrate. And so in a lot of pre-workout formulations, you'll see citruline and or some form [00:08:00] of nitrate, which are there to purportedly be the nitric oxide booster that therefore helps you get a pump and so on and so forth. So, yeah, that was my trajectory with the supplements. And the reason I saved the nitric oxide related stuff with citruline and bee root for the finale for the dissertation is because there's a lot more meat on the bone, right?
So if you wanna measure caffeine's effects, like you could pretty much do a caffeine study. If you can just measure how high somebody jumped, if you wanna do a creatine study. If you have a bench press, you're good. But yeah, with this study on nitric oxide precursors, citraline, and bee root juice, that's where you can really get into some more nuanced stuff in terms of neuromuscular function, but also more importantly different indices of blood flow.
Because there was this kind of prevailing concept that nitric oxide obviously does play a role in vasodilation and therefore blood flow in certain conditions. The idea was before a workout, get some kind of [00:09:00] nitric oxide precursor, increase the bioavailability of nitric oxide during the workout, get better blood flow, deliver more nutrients, clear, more metabolites, that's the line of thinking a lot of people were interested in.
And so, of course in my dissertation work, I measured blood flow at the kind of conduit artery level. So we were looking at the femoral artery specifically. Also looked at blood flow in the micro vasculature using nears near infrared spectroscopy. But if you look deeper in the bee root literature, you'll see other stuff that's more more related n to neuromuscular function.
So if you look at a lot of the stuff with bee root influencing, for example, power output during high velocity movements, that's where you start to see people talking more about perhaps nitric oxide having an effect that increases calcium release in the sarcoplasmic reticulum, allowing for some of these.
Explosive, powerful high velocity movements to be done with a greater level of force. So that's where we brought in the dynamometer. [00:10:00] Now in my study my, my dissertation work, obviously there were multiple mini experiments mixed in short-term, long-term, all that kind of stuff. Actually we didn't do it like a super long-term component, but there, there are multiple studies mixed into it.
But the main take home point, honestly, for my dissertation is that neither the citrulline nor the beet root juice had a major impact. Whether we're talking about blood flow or the parameters of muscle function that we measured on the dynamometer. Now normally you would look at that and say, crap, we struck out.
I guess we don't know anything, but I actually was of the opinion that it made sense in hindsight why we didn't see much happening. And so number one is, we, you brought up the question about mechanisms. Like I said the kind of most superficial me, like I remember when I first got into supplements, I'm walking through the GNC at the time and I see a big display for Nno explode, and I see Ronnie Coleman and his biceps look like they're about to pop out of his skin veins [00:11:00] everywhere.
And so the first kind of generation of pre-workout products, which were more arginine based rather than citruline or nitrate, they laid out this very supervi, superficial mechanistic explanation that I mentioned. Right? So more nitric oxide, more blood flow, it'll be great, what could go wrong?
But the reality is, you know now that I've had a little more exposure to, like, I, I did a postdoc in evolutionary anthropology. You come to find that the, when there's like really important stuff the body needs to do, it tends to get it done when it's in a healthy state, right? And so what I'm getting at there is the fact that, if we look at some of these supplements trying to impact blood flow in people who have impaired endothelial function, impaired vascular function, we often do find a beneficial effect of things like nitrate or citraline.
But when I'm grabbing healthy 20-year-old college kids who are walking 12,000 steps a day, 'cause they're on campus and they have no d like no negative effects preexisting in [00:12:00] terms of endothelial function or vascular function, turns out when they exercise their blood flow is where it needs to flow.
There, there's just nothing wrong there to correct and certainly nothing that a few grams of citraline is gonna rectify. So on the blood flow stuff, we really didn't find much of an impact because blood flow increases during exercise and if you have a healthy vascular system it increases enough to get the job done.
On the muscular side, the neuromuscular side ultimately I think what happened was we were looking, it, one of the great things about Isokinetic, dynamometry is you get to control everything, right? You get to control the velocity of movement. You get to control the range of motion. So much control to be implemented there.
The downside is you need to pick a velocity. That is how it works, right? That is the isokinetic portion. And as more research came out, between the time I planned my dissertation and the time I finished my dissertation it turned out that some of these nitric oxide precursors, including bee root [00:13:00] seemed to specifically.
Be enhancing force production in high velocity movements. And so there's some really cool studies where they actually would look not just, do something explosive versus do something outta fixed velocity, but specifically doing it at different fixed velocities, going from very rapid to very slow.
And normally, with isokinetic dynamometry, people who are more strength focused, like me, you would always think we need to make sure we're going slow enough to actually see some big force production on the concentric actions. Right. The whole force velocity curve. But in this case, I think because I went I didn't go super slow, but I went slow enough that we missed that window of high velocity movements where nitrate seems to have the biggest impact.
And so one of the biggest takeaways from me that I arrived at after my dissertation work is that. With beet root and nitric oxide precursors as a broad class of supplements, I think we probably put [00:14:00] way too much emphasis on this blood flow oriented mechanism, and probably not enough on the effects that nitric oxide has on neuromuscular function and specifically the odine receptor and ultimately, in effect, that allows greater release of calcium from the sarcoplasmic reticulum.
So, so that was my big takeaway was I wasn't convinced that these supplements are useless, even though we kinda struck out in terms of our primary finding. However, I think that if you're a lifter, the findings convinced me that the applications are a lot more nuanced and narrow than I previously thought.
I used to think, Hey, get some more blood flow. No downside, right? It's gotta be good. And in hindsight I'm much more convinced that this has a lot more to do with excitation, contraction, coupling, and calcium release more so than just blood flow. And I think that depending on the type of exercise you do and your training status, it may have a pretty big bearing on how much you [00:15:00] really get out of it.
Dr Mike T Nelson: Yeah. It seems to sell any supplement. You need a single simple physiologic story to tell regardless if you have any data or not. It just seems like you could, the blood flow story has been around for. Ever and at face value to most people, you pull off the street it makes sense, right? Like you said.
Dr Eric Trexler: Yeah. Hey,
Dr Mike T Nelson: if we can get more blood flow, Ooh, everybody likes a good pump. What is the pump? Oh, you've got more blood flow in the muscle. So, oh, look at this little thing. Nitric oxide, Ooh, this is the main regulator. All that stuff is true, but we tend to forget that. I've often joked that physiology has every bad engineering word, like it's an isotropic, it's chaotic, it's redundant.
There's multiple mechanisms going on, and then you add that most of the time the local control will override all these systemic effects, which in some way is a brilliant design because what's locally going on is probably mattering [00:16:00] the most for the thing you're trying to do. And that rarely do we get something like bi alanine or creatine.
It has, relatively simple story. We've got literature to show that it actually worked out. Like the physiology story we attached to it in general is pretty true. That's, I think those are the exceptions much more than the norm.
Dr Eric Trexler: Yeah. Yeah. And when you look at for example, something like nitrate especially in a source like beet root juice, that has naturally occurring antioxidants, which also have kind of a synergistic effect of extending the half-life of nitric oxide.
It has a much simpler story if you're just focused on like, I know some people like to consume more beets or more beru juice just as a good habit for supporting general cardiovascular health. Sure. And that ends up being a much simpler story. Yeah. Where, yeah.
There, there are some, there is some benefit there in terms of facilitating cardiovascular function more broadly, [00:17:00] especially when there are impairments present. There's also, there's research in endurance activity where we see a little bit more, what you might call mitochondrial efficiency at, after people are consuming high nitrate beet root juice.
So, we tend to find some advantages there. But yeah, when it comes to your pure lifter, it's not to say that there haven't been studies identifying benefit, it's just that those benefits are relatively narrow in scope and whether or not you would call them worth it really depends on what is your kind of baseline physiological state and ultimately how much does a very tiny impact really matter to you.
And so that's something that's, that whether it's worth it is always gonna be in the eye of the beholder.
Dr Mike T Nelson: Yeah, and I think, correct me if I'm wrong, but for nitrate supplements in general, they have to probably be taken, what, two, three, maybe four hours before exercise because of the way it gets [00:18:00] circulated.
And I think it goes back through the saliva and gets converted and it's not in the pre-workouts, I would see these people taking their vaso explode or whatever, like in the locker room before they're going out to, to do their lifting. And I'm thinking, man, even if it's just caffeine that's helping that on an empty stomach, peak blood levels of caffeine are 30 to 60 minutes, so I'm like, ah, even if it's the nitrates are helping, it's probably by the time you're done lifting.
Dr Eric Trexler: Yeah. Yeah. And that's one of those things that I get so many questions about that when talking about nitrate, the. The reality is, you're gonna consume your nitrate, like you said, it's gonna take first of all, there is no like straight from nitrate to nitric oxide. That's generally not how it works.
We're trying to get it from nitrate to nitrate. Two nitric oxide. Nitric oxide has a half life that is basically the blink of an eye, which means you have to have nitrate abundant and present for [00:19:00] instantaneous use of nitric oxide that's actually gonna be generated. And so what you do is you consume nitrate, and like you said, over the course of like two or three hours, it's gonna be getting converted into nitrite.
And part of that process is this weird kind of recycling circuit where you ingest it, it goes into the GI tract, it goes back into like the salivary circulation, and then you swallow that and it's this weird revolving door. But the reason that it exists that way is 'cause the the bacteria in your mouth, in your oral cavity actually play a critical role in facilitating that conversion of nitrate to nitrite.
And so, as a result I get a lot of questions of, well, what happens if I use really strong anti, anti, anti-microbial mouthwash. That, yeah. It says on the label, kill all those
Dr Mike T Nelson: little converting guys.
Dr Eric Trexler: Yeah. It says on the label kills 99.9% of bacteria. Right. And so people say, well, then what happens?
And the answer is, you really nullify the effect of that supplement or any [00:20:00] dietary nitrate that you're consuming from vegetables in your diet. So that's really important. And if you run a study like I did on nitrate, you have a sit down with every participant Oh, yeah. Beginning to say, I'm begging you not to use, like, I, I know you're gonna look at says, don't do this, don't do that.
The one that I need you to take more seriously than anything else as if your life depends on it, is please do not use antibacterial mouthwash for the duration of this study. But, then I'll get people asking them, well, okay, what if I brush my teeth and what if I just, for whatever reason, there's some research showing you if you just spit a lot in the couple hours after you take your nitrate, that actually does impair the efficacy a little bit.
But nothing is nearly as as strong in a negative way as using an antibacterial mouthwash. But yeah, so I would get all these, and then people would ask me questions of like, well, does that mean I need to like swish it around in my mouth more? Like if I drink it too fast, will it not work? I'm like, no.
Like, you don't need it to necessarily interact on the [00:21:00] first pass, but you do need to give it that two or three hours to let that whole kind of cyclical process happen. So, like you said, yeah you'll have people who, they'll be sitting in the locker room gym saying, yeah, I'm gonna take this.
So I get a crazy pump and it's got some nitric oxide precursor. Especially if it's nitrate based citruline, it has a much shorter yeah, it's
Dr Mike T Nelson: different. Much
Dr Eric Trexler: shorter period. Yeah. But even citruline usually you'll go 30, 60 minutes before. But yeah, if, a lot of people they'll take, if they're taking anything nitrate based and then walking into the gym, they might not even be close to getting that effect until they're already showering and on the way home, so, yeah, that timing is a big component.
Dr Mike T Nelson: Yeah. I proposed this to, I, I'm blanking on the guy's name. It wasn't Andy Beat Root, but it was another guy who's done a lot of research on beet root supplements at one of the A CSM talks a couple years ago. And if it's being converted by enzymes in the mouth, do you think you could do like a.
A gum or something that's like [00:22:00] a prebiotic for your mouth to increase conversions or do testing or anything like that. Is that enzyme really like rate limiting in any sense of the matter or it just doesn't matter really?
Dr Eric Trexler: Enzyme or bacteria?
Dr Mike T Nelson: Oh, I'm sorry. Bacteria.
Dr Eric Trexler: I'm sorry. Okay. Yeah,
Yeah.
'Cause yeah, that's always
Dr Mike T Nelson: the big, I was in conversion, I said enzyme by mistake.
Dr Eric Trexler: Yeah. No. But that's always the big the big selling point of nitrate, right? Is that it's the non enzymatic pathway, right. Versus citraline. But yeah, honestly you raise a really good question that has bothered me for a while and I haven't seen great data on it.
Like I
Dr Mike T Nelson: haven't either.
Dr Eric Trexler: There, there's really good research to showing you how to mess up. The balance. Do
Dr Mike T Nelson: we know how to screw it up?
Dr Eric Trexler: Yeah. Yeah. We know how to mess up that balance in a way that kind of nullies the effect acutely. But I've never seen really good research on how long it takes to repopulate that kind of oral microbiome environment that you need.
And I've also not seen any ways to [00:23:00] specifically, fast track that process. But yeah, it would be that would be a smart delivery system if it's feasible, is to have Yeah. Some kind of probiotic gum where, they, we've identified these colonies that, that are critical in the process and they have been identified.
I just don't have, I'm not good at memorizing bacterial strain names. No, I'm the worst at
Dr Mike T Nelson: memorizing bacteria names.
Dr Eric Trexler: Yeah they're always long and they're, yeah, they're very convoluted, but but we do know what they are, for sure. And so, yeah, if we can put those in a shelf stable, gum type product or a capsule that you just break and pinch your nose and put it in your mouth.
And it certainly would be interesting because that, that is one of the things that I do hear people who are interested in nitrate they complain about is they're like, well, okay, I am very serious about my oral hygiene and I do like to use an antibacterial mouthwash as part of that oral hygiene routine.
But I would also like to get these benefits of nitrate. And for [00:24:00] those individuals, I've never been able to give a very good recommendation other than how would you feel about an oral hygiene routine that is still rigorous but doesn't have such a powerful. Broad spectrum, antibi, antimicrobial type element to it where it's just, a lot of brushing and flossing and things like that.
But I, believe it or not, I'm not a trained dentist, so that's usually where I stop is like, hey, maybe, it is, it's really fascinating because, people get dietary nitrate in their diet, even if they're not thinking about it. Mm-hmm. Especially if you have, a lot of leafy greens in your diet and things like that.
And what there, there is some research showing that people who use, really strong mouthwash that kills bacteria in their mouth, they actually do tend to have slightly higher blood pressure. When we look at these like huge population level data, now we're talking about a few millimeters, mercury, right.
We're not talking about anything that you would consider in my opinion, to be like physiologically or clinically relevant, but it is an interesting look at how [00:25:00] delicate that little system is and that even that, that change that. I think we've been accustomed to not think twice about it 'cause it's such a normal household product.
And such a, commercials all the time for Listerine or whatever. You don't really think about like, what are the ramifications of using this? It's like, it feels like a decision on the same level as switching your toothpaste. Right. Which for me, I wouldn't think twice about, I just look at whatever they're marketing.
I have no idea if it's true. This one is for tartar control. This one makes your teeth wider. One sounds
Dr Mike T Nelson: good.
Dr Eric Trexler: This one is for everything, and I'm like, oh, everything sounds nice. But yeah, I mean it's a really fascinating little look at our physiology and it's, if you're just into physiology for its own sake and how cool the human body is it is really fascinating to see how a little change like that actually can manifest in something that we can meaningfully measure over time.
Dr Mike T Nelson: Yeah. It reminds me years ago, God probably. 15, 16 years ago I was doing my PhD and some people I knew on my list [00:26:00] were dentists and they said, Hey, we've got this cool conference in Cancun and we want you to come be a speaker. And I'm like, great. I don't know jack crap about dentistry, anything like that.
I have no idea. They're like, no, just want just a general talk on, fat loss or metabolism or something. I'm like, great. Sure. I'm like, you're gonna pay for it. Oh yeah, all inclusive. Went to Cancun, stayed at the hotel and it was great. Like dentists are actually like super fun to hang out with.
We had some fun parties and I was surprised that the talks were actually really good. Like they were actually very academic, at least this particular one that was sponsored by, I think a XCL at the time, which was a xylitol supplement and they had some really interesting research showing about how it.
Potentially changes pH maybe different bacteria breaks down biofilms. And this was like a long time ago, and I kept waiting for this information, which appeared to be pretty solid, to be more mainstream. And maybe it is, and I just have [00:27:00] never seen it again. But it always fascinated me how there's all these sub niches somewhere if you look hard enough of people who are really interested in these things.
So maybe someone in that little vein has come up with, things that might be beneficial and cross over to the sports domain, and they're just separate silos that haven't interacted. I don't know.
Dr Eric Trexler: Yeah. Yeah. No it's really fascinating and I think with any supplement or any dietary ingredient that's included in supplements, the first question is always, it's a sequence of questions. Is there a plausible mechanism? Does it appear to work? Yep. And how do we maximize its effect? Right. And so when you talk about something like nitrate, even though I've been, a little bit lukewarm about it so far in this podcast, there, there's no question. There are multiple pertinent physiological mechanisms through which bee root juice or any other source of nitrate could have an effect.
There is research showing ergogenic effects predominantly an endurance type exercise, but also some in more strengthened power type exercise. Looking [00:28:00] at things like power during high velocity, muscle actions, and also some instances of muscular endurance in like reps to fatigue tests and things like that.
So it clears those first two bars of is there a plausible mechanism that makes sense? Yes. Is there an observed effect with a magnitude that seems reasonable based on those mechanisms? The answer is yes. 'cause there are some supplements out there that I've got circled in my mind where. The effects we see in preliminary studies are just the magnitude makes no sense based on the purported mechanism, which leads me to believe there's some funny business going on in the quantification of those magnitudes.
But with nitrate, no, it all lines up. This is rigorous work done by many labs across the world. And then the next question, like, like I said, is ultimately how well, how do we maximally leverage this? And like you said I think there's some interesting ways that you could. Hypothesize that instead of just, trying not to screw up the oral microbiome, maybe we try to improve the oral microbiome.
But then of [00:29:00] course the question is what are the downstream effects of that? And I have no idea. Right. So like,
Dr Mike T Nelson: yeah.
Dr Eric Trexler: Could you imagine a scenario where someone says, oh, I chewed this gum to change my oral microbiome to bolster those bacteria to almost like a super physiological level for this conversion process.
And I started getting more cavities, or it started to re, eat away at my enamel, or now I have bad breath, like, I have no idea. I wanna be very clear, I have absolutely no idea if any of those three options are realistic. Yeah,
Dr Mike T Nelson: I don't either.
Dr Eric Trexler: But it's one of those things you always gotta think about with these downstream effects.
Especially when you're talking about, like you said, you go to, you talk to a dentist about teeth and it's not just like, Hey, don't chew rocks, and they'll, they shouldn't break, right? You're talking about. What is needed to create this environment in terms of the pH and the bacterial levels and all these things that ultimately are conducive to good gum health, good tooth health, and hopefully not bad breath, right?
It's like this whole, it's, it really is an environment or an [00:30:00] ecosystem and so you always have to be cognizant of any time that you try to go in and change something like that, who knows, you know what would happen? Certainly not me.
Dr Mike T Nelson: Yeah, and I think even on some other blood flow tests, like part of my research I did was on energy drinks and looking at metabolic flexibility and HRV and stuff.
But one of the studies, and unfortunately the bane of my existence was not able to get published. I did a bunch of FMD data, so flow media dilation,
Dr Eric Trexler: right?
Dr Mike T Nelson: So for people who aren't familiar, we use a brachial. So you put your arm in this device, you clamp down on your forearm with a blood pressure cuff for five minutes.
You image the vessel in the upper arm and then you let the cuff go and you've got this huge inflow of blood flow, which then sees shear stress along the wall, causes it to dilate. And so I was curious to see if energy drinks messed that up because, back 10, 11 years ago, everyone's like, oh, energy drinks are gonna kill us.
And there's very little data at that point. And fortunately ran the study, did all the initial [00:31:00] analysis and everything was good and. When I went to publish it, basically my standard deviation of the pooled data was super high. And my advisor's like, you suck as a sonographer. This is bull crap.
Like you, there's no way we could publish with this high standard deviation. I'm like, oh man. I did all the trials, I did all this practice, I did everything. And I started looking at the data individually because we had pre, we had energy drink condition, and then we had post or we had three conditions.
We did the baseline when they did their body comp and then it was intervention. So they either got the energy drink or they didn't, which was, randomized and placebo controlled. So we had FMD over three different time points. Two of them not energy drink. One of 'em was an energy drink.
And when you looked at all the data and you pooled all of it? Yeah, like the standard deviation was pretty high. But then I started looking at individuals and on both of their baseline conditions, so to speak. I got like the most extreme outliers you could ever imagine. 'cause these are all like normal, healthy individuals.
These are [00:32:00] not vascular disease or anything like that. And it didn't change a whole lot across individuals, but some of their baselines were way higher than other people. So some of these people just dilated like crazy. Other people were still within the norms. They weren't pathologic, but they just didn't dilate as much.
So unfortunately when you pull the data, you get this high standard deviation, but in my head I'm like, oh, maybe I don't suck that much as a stenographer. I just got unlucky and got like the extreme ends of a healthy population and therefore my argument was we should still try to submit it and publish it and show, if you look per individual, here's the range we got, here's our stats.
It is what it is. Like it's not invalid, it wasn't sexy and the SD was high. And so that. He never even allowed me to publish it, which is a bugger, but I think it did.
Dr Eric Trexler: So he allow you to, wouldn't allow you to submit it for
GMT20251017-165833_Recording_640x360: publication?
Dr Mike T Nelson: No, he wouldn't even allow me to submit it.
Dr Eric Trexler: I was gonna say I've, I would almost be really [00:33:00] thrilled and encouraged if you got a thorough enough review that they were nitpicky about the baseline standard deviation.
Dr Mike T Nelson: I'm like, I guarantee almost no reviewer is gonna look at this.
Dr Eric Trexler: No.
Dr Mike T Nelson: Like it sounds horrible to say, but Correct.
Dr Eric Trexler: Yeah.
Dr Mike T Nelson: And the worst part about it was that was my third study, right? So for the PhD, how to do three complete studies, I'll be human studies, et cetera. So now I didn't have a third study, which meant it literally added another three years to my PhD just because of that.
But it also emphasized to me that when you're dealing with normal physiology, I don't think we understand real well what are the ranges that can be normal. And I think they're much wider a lot of times than what we realize and. Almost nothing when you do actual human measurements lines up exactly.
Like all the books tell you.
Dr Eric Trexler: Yeah, no we do convenient sampling of what is ultimately a non-representative sample. And we often pretend that [00:34:00] represents the spectrum of human physiology. Yep. Right? Yep. So essentially we know what it looks like for people who have a little bit of free time, who are between the age of 18 and 23 who live within five miles of a college campus.
It's pretty much the understanding of human physiology that we've developed. No, I totally agree and this is something that comes up a lot. I've been very privileged, a lot of times people get into exercise science and they want to do something involving elite athletics, and those opportunities tend to be few and far between.
Definitely. But I have been really lucky to be able to get some exposure to working with, nFL athletes preparing for the combine. Retired NFL athletes, high level college football players extremely elite college basketball players, we're talking about top 1% of top 1% kind of global athletes, right?
People who have signed a hundred million dollar deals because they are that different. And it never ceases to drive me nuts when I'll, talk about [00:35:00] something that is just like slightly outside of the norm for a 20-year-old college student. And immediately people on the internet will be like, that's physically impossible.
No human is like that. And I'm like, I need you to understand that the people who make over their career $170 million playing elite sport are not like you. Or your training partner or your neighbor down the street,
Dr Mike T Nelson: they're not even close.
Dr Eric Trexler: They are fundamentally different. And they are still also part of humanity.
So we need to understand that yes, most data will be near the mean, but at the end of the day we have, so for so many different physiological parameters and characteristics, there is so much variation. And ultimately that is part of what makes sport cool. It's part of what makes clinical conditions devastating.
And it's, that is the human condition is this tremendous amount of variability that we rarely actually observe and measure and report.
Dr Mike T Nelson: Yeah. And that's also what is both [00:36:00] extremely fascinating and maddening at the same time, like, I remember I said this in the podcast multiple times, like talking to my buddies, Dr.
Ben House and Dr. Tommy Wood, and we're all like, just going about. When you get the chance to work with sort of the elite, we all agreed that it's hard to explain how freaky the freaks actually are. Yeah. You know what I mean? If someone would have explained that to me 20 years ago, I'd be like, that's bs.
There's no way. Like that's not happening. And then you see the actual data, you do the measurements yourself, or even if you're just on the sidelines watching NFL players that are over 300 pounds move ungodly fast. You're like, if you saw this human standing in the grocery store, you're like, yeah, that's a freak, but there's no way that guy is moving that fast.
And then you see it and you're like, holy shit. That's insane.
Dr Eric Trexler: Yeah. Like I, I think people are, start with the NFL. I think people have an easier time. Understanding it, but they still miss it by a lot in the sense that like, [00:37:00] there are people in the NFL that weigh 307 pounds who are faster than you were in high school.
Oh, no. When you weigh one 50, right. If you did a 40, 40 yard sprint against them, they would beat you at your athletic prime when you weighed 150 pounds.
Dr Mike T Nelson: Yeah.
Dr Eric Trexler: Yeah. It's, I always hear these things about, what is the, no one actually burns 6,000 calories a day. Have you measured a seven foot tall person who runs all day every day?
They do. They burn a tremendous number of calories that, that you couldn't even believe. Yeah, it's it's really cool to be able to get a window into that. And I think the first time it struck me, there was a guy on my wrestling team in high school who ended up winning a Super Bowl as an offensive lineman.
So he was our heavyweight. And Mike, you ever watch any like wrestling freestyle? Yeah. Oh yeah. Yeah.
Dr Mike T Nelson: It's crazy.
Dr Eric Trexler: When you watch a wrestling match between the lightweight, 110 pound wrestlers, and then you look at the 160 pound wrestlers and then the 280 pound wrestlers, [00:38:00] the moves that they do are different.
The sport looks different based on, the size of the individuals. And I just remember one time watching this heavyweight on our team who weighed about 270 pounds at the time do a move that I had never seen a person over 150 pounds ever try and do it with such grace and flawless execution.
And it was right on the boundary of the mat. So he did that thing where you just drag the tips of your toes, that two point take down before you go out of bounds.
Dr Mike T Nelson: Yep.
Dr Eric Trexler: And I remember it striking me as just like, and this was a person I would see in practice every day, but there's just that, that one flash of a moment where you go, oh my god.
This is different in a way that I can't really convey with words. And so then it's like no surprise that, 10 years later he is got a Super Bowl ring and you're like, yeah, that checks out. I get it. And no surprise, he was a guard, right, who is somehow 305 pounds, but also has the footwork, the [00:39:00] agility, the speed to pull and hit a hole before the running back gets there.
Yeah. Only someone like that.
Dr Mike T Nelson: Yeah, I remember, I won't say the guy's names, it's probably not PR public, but worked with a couple. NFL guys just trained him in the off season and they were doing box jumps and he had the two guys, one on his left, one his right, and the guy on his left, he was like doing some other stuff with him because he had a, an ankle injury.
And he is like, okay, whatever you don't do the box jump, don't jump up with both feet. You've got a left ankle injury. I was working with the other guy was, I don't know what the box was, like 40 inches, three six inches or something. It was pretty high. And so he is working with the other guy, doing the boxing jumps, doing the landing.
He looks to his left, he sees the guy with the injured ankle standing on top of the box and he yells at me. He goes, what the f are you doing? Like I told you not to do two footed jumps. He is like, oh, it's all good, coach. I did this off of one leg. And he literally did it off of one leg. And he's like, oh shit.
Okay.
Dr Eric Trexler: Yeah, no it's amazing man. And that's another thing that, it drives me nuts, is I don't [00:40:00] want to like, pr on and on about this, but
Dr Mike T Nelson: yeah.
Dr Eric Trexler: One of the papers I published was about fat free mass index in high level college football players, and I published it.
Yes, I remember that one. I published it and then immediately everyone said, Eric Drexler, you gullible idiot. They must be giving away PhDs because clearly all these people are on steroids.
Dr Mike T Nelson: Right?
Dr Eric Trexler: All
Dr Mike T Nelson: of 'em,
Dr Eric Trexler: of course. 'cause none of my training partners are as big as these guys on like a high level SEC football team.
Right. Who play defensive linemen are about to make 20 million a year. Okay, fair enough. I said, but but man, like I remember bringing in a retired NFL guy who looked like a Greek stat, like, just like he looked like a Greek god carved outta stone. So muscular, enormous did a dexa with him and sat down and was talking to him about, what his diet, his training, stuff like that.
And I was like, first of all, holy crap, you're huge. And so my first question was like, what does your training program look like? And he looked me dead in the eye and said, I forget the [00:41:00] exact number. It's been a long time, but it was, I haven't worked out since I, the day I retired, which was like five to seven years ago.
And so just activities of daily living allowed this man to maintain a physique that he looked like a very good natural bodybuilder. And similarly I've talked to someone who coached A NFL running back who could not do. A lot of upper body work because his arms would get so big, he couldn't comfortably hold a football with just a small amount of strength oriented training with upper body.
And so he said you're full of crap. You're just trying to get outta training, do this work. And lo and behold, his upper body like blew up and they could no longer geometrically fit the ball in there the way it needed to fit. And so then they detrained, right? Yeah. Like you have to and then there was this one guy who was getting ready for the combine, a high level running back who looked like not only a good, he looked like an elite natural bodybuilder who that day could walk on stage and win a high level pro show conditioning and [00:42:00] everything.
And we asked him after he was training, it was combine prep, right? So they're in there from like nine to five. Yeah. Just training. So it was like, toward the end of the day, what'd you have for breakfast? First of all, he looked at us like, we asked him what his favorite color was. Why? Why would that be relevant?
Why do you care? We said, what'd you have for breakfast? Nothing. What'd you have for lunch? Nothing. What have you been eating or sipping on during this like eight hour training session? Water. And like, again, I've got people telling me, anyone who looks like that must be on steroids. And I'm like, steroids, we can't get this guy on breakfast.
Dr Mike T Nelson: Right?
Dr Eric Trexler: Like, you think he's in there like managing this careful steroids cycle when we just can't get him to like eat a thing before 5:00 PM So yeah. It's so many anecdotes. If you talk the moral of the story is I beg listeners to believe any person you've talked to that works with these elite athletes, the spectrum, the variation in human ability, physiological capacity is just so vast.
And [00:43:00] it's important not to not to lose sight of that and put all of achievement into this tiny little box. 'cause ultimately what a boring way to enjoy sport. What a boring way to enjoy physiology at the end of the day.
Dr Mike T Nelson: Yeah. That's why the kind of the. Netty or not? Arguments always just drive me bonkers because I am sure there's a lot of people using a lot of drugs who lie through their teeth.
I have no doubt that is a hundred percent true, but I've also seen enough freaks, so I don't think we're all lying to me either to know that if you take a big enough population, you're gonna have some of those freaks included in it too.
Dr Eric Trexler: A hundred percent. Yeah. It's, and that's the biggest thing I think at the root of this is that at the end of the day, Mike, I have a lot of passion for statistics.
Dr Mike T Nelson: Yes.
Dr Eric Trexler: Statistics are in, are inherently unintuitive. Yes. So we, it's very easy to understand that most people should be about average. But it's [00:44:00] very difficult to convince people that not only is it possible, but it is expected. There should be people out there who are more than three standard deviations from the meeting.
Yes. For a given,
Dr Mike T Nelson: that's a given a big enough population.
Dr Eric Trexler: Exactly. Yeah. So when people see an outlier and they say, well, how could this be a better question is how could it not be? Mm-hmm. If we expect this to be normally distributed and we have a population of 8 billion people it is not only possible, but a probability that we will run into those things.
And it's, you will live a happier life if you marvel at it rather than be suspicious of it. That's my general approach.
Dr Mike T Nelson: Yeah. And my bias is those are the people we should study. And even if it's only case studies, and I know everyone's gonna lose their mind of like, okay, studies are such a low thing of evidence.
But like there, there's, I think. Physiologic gold if we can figure out like what's going on with those people, which is why a lot of times these weird genetic [00:45:00] pathologies are so fascinating. Like not many people have me car's disease, but when they do, holy crap, that just confirmed everything we thought we knew about glycogen because they're missing the enzyme.
They can'ts store glycogen or they can't break it down, so there's not a lot of 'em. You're not gonna, you're gonna be hard pressed to get high statistical relevance on these weird genetic diseases. But many times there's countless things in physiology where we learned more from those handful of individuals than we did from all these great high powered studies.
And again, you need both. I'm not arguing one is better than the other, but I think in this rush to always publish stuff and to do bigger trials, which are a hundred percent needed, I think sometimes these cool little case studies get thrown by the wayside.
Dr Eric Trexler: No, a hundred percent. And my PhD was actually in the school of medicine at UNC.
And so it was a very interdisciplinary program where, we had people there who studied all sorts of genetic conditions specifically [00:46:00] ones that impact movement. So a lot of different neuromuscular conditions. And we took a grant writing class with all of us together. And it was always easy for me, if I'm writing a paper about muscle sarcopenia, massive clinical impact in, impacts this many zillions of people, this many zillions of medical expenditures every year, like the grant writes itself.
Same thing if I'm talking about weight regulation, obesity, number one cause of this, that, the other thing, right? And so the, making the case for impact in terms of human mortality, morbid morbidity, in terms of economic hardship on the healthcare system. It was all there. But a lot of my colleagues, they had to really lean into exactly what you're describing, not when I say had to, it's not that it was some kind of strategy, it was just, it's hard to convince a grant funding agency, yep.
We need to do this work on this ultra rare thing that impacts a low number of people. And you really have to help those funding agencies recognize, [00:47:00] number one, how much we learn from studying these very anomalous conditions. And number two, how even though it impacts a small number of people, it may ultimately end up being treatable.
And the impact on that small number of individuals is absolutely massive. And so there's, there is a huge, human cost to not doing this work to better understand these rare things. So yeah, I totally agree that those are really unique research opportunities that unfortunately don't, they don't, we don't have as many opportunities for people to dig into them because of those funding constraints.
Dr Mike T Nelson: Yeah. Last question on blood flow, and we'll transition a little bit quickly to some of the stuff you've done with NEAT and et cetera. My bias, if you want a bigger pump, like just for God's sakes, don't be dehydrated. Maybe have some fluid and some electrolytes, like, don't have your blood plasma volume be low.
You can make an argument for low level aerobic training, things like that. Maybe sauna [00:48:00] as long as you're not dehydrated, et cetera. And then the second part to that is over time, I think that if you, maybe, if hypertrophy is your only goal and that's the only thing you care about. I could see an argument of, getting a pump, not getting a pump might be beneficial.
But I, I think the more you move into athletic development, and even just on my personal experience, the times I've had, let's say the best pump, my performance has been worse. I think it actually occludes your ability maybe to do more reps, to do more work, to lift a little bit heavier. And then maybe it's because that muscle isn't relaxing as much as it should, right?
It's staying more, for lack of a better word, tous or on, or whatever words you want to use that is ven trapping more fluid in there. So your performance, like you were talking about rate of power and this on and off again, like there's old [00:49:00] Russian research to show, like their high level athletes could relax their muscles faster.
Wasn't necessarily all about contraction. So to me it does. Would you agree that these are like two. Opposing camps almost depending upon what your goal is.
Dr Eric Trexler: For me at the beginning of my PhD, I was very bullish on the idea of a pump and like, oh yeah, get a better pump. It'll help with muscle growth.
And, but the more you start to dig into that I'm not saying
Dr Mike T Nelson: how much data in
Dr Eric Trexler: that, yeah, it's, I'm not saying that it can't be true, right? Or that it's like fundamentally implausible at face value. But you start to look into like, well, what is the evidentiary basis for that particular belief or established piece of knowledge?
And it's shockingly limited, shockingly weak. And so that, that's my, one of my biggest takeaways from my dissertation work, was I was like, now that I think through it more carefully, I'm not even necessarily convinced that a pump is. [00:50:00] Has a high probability of aiding, like you mentioned, performance.
It doesn't even really make any sense. Right? But even for hypertrophy it's still a, there's a lot of gaps in that story that you have to fill in. And we know, we, when we talk about a pump, usually we're describing a totally subjective sensation in which the muscle feels particularly full greater in volume tighter.
And a big question when it comes to the muscle pump is where exactly is the fluid? You know what I mean? In the, okay, within the muscle, fine, but where within the muscle is it actually putting any kind of pressure or stretching stimulus on the correct tissues that it's actually gonna ultimately stimulate any kind of signaling that would ultimately promote greater growth?
I, no one's really. Laid out that whole framework from start to finish with a granular enough level of [00:51:00] detail to really satisfy my curiosity on that. And again, I'm not saying that I've worked through the whole thing and concluded it to be completely false. I'm saying nobody's really laid out, step A, then B, then C, then D in a way that is cohesive and actually relies on evidence from muscle tissue.
Usually they're gonna end up leaning on evidence from non-muscle cells that are exposed to some kind of stretching or, increased volume that kind of induces a stretch on the boundaries of the cell, which causes this, that, the other thing. So I'm really intrigued by it and the short answer is.
It's hard to imagine a, an immediate benefit for performance. Like you said, there could be a detriment, and I'm sure we've all had those instances where you get a pump in the wrong muscle and you're like, this actually is painful. And I am, I'm demonstrably training worse, and I wish this pump would go away so I could train more effectively.
Like we've all had that. I think I've heard a lot of PED users talk about getting pumps in their lower [00:52:00] back mm-hmm. That, that are very frustrating and ultimately lytic rather than genic. Yeah. And then at the end of the day for hypertrophy, I'm pretty sure don't quote me on this, but I'm pretty sure Eric Helms is advising a doctoral student who is really zeroing in on that question Cool.
For their dissertation. So I do believe we'll be getting some more direct evidence on that sooner rather than later. But yeah, the whole kind of traditional narrative of. You take the nitric oxide booster as a young, healthy person with a perfectly functioning vascular system, you get a bigger pump and then you grow more muscle.
There's a lot of missing steps in there and a lot of missing evidence to tie that whole thing together.
Dr Mike T Nelson: Yeah, and I'll put a link up to Dr. Mike Roberts, who we had a big podcast about muscle hypertrophy and everything too. 'cause his lab's done a lot of that stuff for many years.
And yeah, I guess my argument in general is for most people we know mechanical tension is the big thing. [00:53:00] And if you're applying overload and you're doing more volume and you're doing high quality work, you're not getting injured. You can do this day in and day out. Nutrition's not a walking trash bin.
Fire. Your stress is not through the roof. After that, like I, drugs aside, everything is just icing on the cake. And if I saw something that drastically dropped their output I don't know. I think you might be going in the wrong direction.
Dr Eric Trexler: Yeah. And I think to me, what it really comes down to, to like lean on a metaphor, right?
So like you said, we know that mechanical tension drives a very substantial amount of this muscle growth stimulus. Yeah. So if you're looking for little low cost, low risk things that allow you to train the same way, but get you a better pump as you do it, fine, whatever. Yeah. Cool. Right? No big deal. But if you are altering important variables related to training or nutrition for the sole purpose of getting a better pump at the [00:54:00] expense of that kind of traditional model of progressive overload, mechanical tension, et cetera, et cetera.
If you're doing that, then it feels to me like you are taking money out of your, like, index fund investment and putting it into a meme stock. I'm like, well maybe let's just like stick with that's clearly tried and true and like we know works. Like, but again, if you if you're still training with your same bread and butter and you're just trying to find other little nutritional strategies to maybe get an extra pump on top of that, at the very least you didn't liquidate your retirement account.
Yeah. Right. Like it's, stick with the stuff that works and is, gonna keep you on that very predictable track. That we know is tried and true. And if you want to try to do some other fun stuff to facilitate that, no big deal. But yeah, when, we've seen this so many times, right?
Like back in the day we're both old enough to remember when people were training in a particular way to maximize their. Acute growth hormone response. Oh yeah. Something like that. And ultimately they were abandoning [00:55:00] some pretty basic key fundamentals that we know work to chase this other thing that ultimately has a pretty unimpressive track record.
Dr Mike T Nelson: Yeah. And Dan West has done those studies, like two of 'em to show that it pretty much doesn't matter much.
Dr Eric Trexler: Yeah.
Dr Mike T Nelson: I still remember an ar Right. I wrote an article for Team me on that back in the day and man, I got so much hate mail for that. Yeah.
Dr Eric Trexler: Were you downplaying it saying,
Dr Mike T Nelson: yeah, it didn't
Dr Eric Trexler: matter time with this,
Dr Mike T Nelson: and everyone just woo, like lost their mind.
I'm like, we've got pretty good data here. And again, like you said, if you can do that and still have overload, still have all the other stuff, great. Go crazy. But we saw everyone just shifting away doing this, what I would say is crazy training, just putting all their eggs in one basket that didn't turn out to be true.
And then you rip the teddy bear away from 'em. People just don't like that.
Dr Eric Trexler: Yeah. Well, my, my. Rigorous evidence-based rebuttal to your article, Mike is for God's sakes, it's called growth hormone.
Dr Mike T Nelson: Right.
Dr Eric Trexler: It's not to [00:56:00] like,
Dr Mike T Nelson: yeah,
Dr Eric Trexler: it's, it sounds really good if you promise not to think about it. So yeah I'm sure that you got all sorts of hate mail.
Dr Mike T Nelson: Yeah. We got about 10 minutes left, but I did wanna touch on briefly some of the work you've done with looking at just overall energy expenditure. And I guess the main question I had was, we know that simply, neat. So non-exercise activity through neurogenesis, like a shocker move more generally works, but I think one of the issues is that people, myself included, although I try not to, it is just human nature to think linearly.
So if we think, Hey, I only get 5,000 steps a day, so Dr. Drexler told me to go 10,000 steps a day, that's gotta be twice as good. So if I do. 15,000 and I do 20,000. Oh my God. Like, this has gotta be like three times as good as my lowly 5,000 steps a day. And shocker, I think you would agree that it, the linearity of that just doesn't [00:57:00] quite play out that nice and neat.
Dr Eric Trexler: Yeah. Absolutely. And so, I, I was really excited a few years ago. I did a 2013, or sorry, 2023. I started a postdoc in Herman PO's lab here at Duke. Did a two year postdoc and then joined the faculty here in a different department. But I had such a great experience working with Herman that I still, I'm in his lab every single day continuing the research Nice.
That we started. Yeah. So we still work, we work together every single day. Yeah. And the work he's done in this area, the reason. I don't know if I would've gotten back into academia if it wasn't. There's an opening in Herman's lab. Mm-hmm. He was doing the coolest research, in my opinion, that was happening in the whole world.
And it was 20 minutes away from my house.
Dr Mike T Nelson: Oh, perfect.
Dr Eric Trexler: And I was like, okay. Like, come on take a hint. Yeah. Do it right. And I'm so glad I did. 'cause just being at Duke the last few years has been incredible. I really love it here. But Herman did a lot of groundbreaking work. Basically getting at exactly what you're talking about, that it's so [00:58:00] tempting to believe in this kind of linearity.
But when we look at so many different examples in human populations and in non-human populations, we find that energy expenditure is a managed budget. It is not something where you just increase one thing and everything else promises to stay the same, right? And so, this goes even to there's research in birds where you would look at, what is their energy expenditure when they're just sitting in the mess in the nest versus when they're actually migrating?
Youd be amazed at how small the total energy expenditure differential is in these totally different phases of their activity level. And it's because when they're sitting in the nest for those, deter predetermined periods of time, they're doing a lot of biological processes that basically get put on the back burner when they're actually, flying around and migrating all day.
What's interesting about primates is, primates compared to other mammals our resting energy expenditure scaled to body size is pretty similar, but our total daily energy is ac daily energy expenditure is actually considerably lower [00:59:00] than other mammals really when scaled to body mass.
And so it's not just a human thing. It seems to be something that evolved pretty early in the kind of primate lineage, which is that we are particularly aggressive about managing this energy budget. And so, we see whether we're looking at hunter-gatherer populations, sedentary Americans sitting behind a desk all day, whether we're looking at elite endurance athletes we see this huge body of evidence indicating that when you go from being super sedentary, like you said, I'm doing 5,000 steps a day.
Eric told me to go up to 10,000. We do see a fairly linear kind of, you do a little more activity, you get a little more expenditure, and it's in a pretty predictable proportion. But when you start pushing that higher, that's where the linearity starts to fall apart. And we start to see, for example if you try to push your activity level super, super high for very long periods of time, what are we gonna see?
Well, you go into the [01:00:00] doctor and you say, well just for ease of, the example, we'll say that this is a woman goes into the doctor and says, well, I haven't had a menstrual cycle in three months. Take my blood. My, my sex hormones are low, my thyroid hormone is low. And we see all these clinical manifestations of what is ultimately just downregulating.
Some of these, noncritical biological processes that cost energy, and so, so it's a really fascinating line of work that I've tapped into here where, you know we have studies going on with various subsistence populations throughout the world. So, we've done previously work with the Hadza the Dawson community the Chimani community in South America.
We have a network of folks who are up in Siberia, down in Southeast and all over the world with groups that are maybe hunter gatherers or maybe do just small scale subsistence farming, or maybe they're pastoralists who tend to small, a small herd. And so we see across all these different lifestyles, [01:01:00] including all the way up to extremely elite endurance and ultra endurance athletes, the same story, which is that when you're going from a.
Very low activity and usually a caloric surplus to moderate. We do see that linear relationship holding up pretty well, but the two things that throw a wrench in it are really high levels of physical activity, or very substantial under consumption of calories. And that's where we start to see these energy conservation mechanisms kick in.
And that's where we start to see, Mike in the fitness world, we see the result of that is very frustrated people, right? Oh yeah. You look at and the thing that's, that really surprises me is I mean I get the pushback to this because it's a very counterintuitive concept. But, then you start talking to people about, all these different areas of research and even just showing them the clinical trials where there are weight loss studies, where they will bring people in, in very tightly controlled conditions and ensure that they were on the treadmill and burn the amount of calories they were told to [01:02:00] burn in this study.
And time again, we find that exercise alone as a weight loss tool. So pairing it with some degree of dietary energy restriction, it never. Basically never meets the actual intended rate of weight loss or the intended magnitude of weight loss. It almost always falls short, sometimes to a fairly large degree.
Sometimes, people only lose 20, 30, 40, 50% of the weight that they were predicted to lose from the expend expenditure that was literally induced and measured in the lab. Where they are measuring the energy expenditure during the workouts. And so it's really fascinating to see how humans manage this energy budget.
And there, there's a whole like, there's a whole like, field of evolutionary biology that, that really leans on. Life history theory that kind of talks through like what are the most pertinent biological resources at a, as at a given phase of your life, and what ramifications would that have on how you manage this energy budget.
When is it time [01:03:00] for wound healing? When is it time for reproduction? When is it time for just trying to survive and shutting other stuff down? So it's a really fascinating area.
Dr Mike T Nelson: Yeah. And I know people will hear, oh, well, Dr. Traxler said exercise is worthless for fat loss then, which is not what you said.
You said that exercise only as an intervention without any caloric control is not the most effective. And it,
Dr Eric Trexler: yeah,
Dr Mike T Nelson: drives me in insane that the fitness industry has to be very polarized, one direction or the other. But we've got tons of data at this point showing. Exercise is helpful with shocker, some dietary control.
Dr Eric Trexler: Yeah. And I think, I always say whenever I'm on a podcast and this topic comes up, exercising is probably the single best thing that you can do for your health. Yeah. If it's not number one it's very close. So we always are, we are an extremely pro exercise research group [01:04:00] because the benefits are just so multifaceted and so widespread, and so.
Significant in magnitude. So we are not in the business of telling people not to exercise or discouraging exercise. However, we do think it's worthwhile to note that, like you said, exercise alone without any other intervention tends to be a pretty poor tool with regards to inducing significant clinically meaningful weight loss.
However, it is worth noting that there are some elements of exercise that can support a weight loss program that is predominantly dictated by either dietary restriction or a combination of dietary restriction facilitated by some of these newer pharmacologic pharmacological interventions, right?
Sure. So now that we see more of these GLP one. Agonist drugs and they are a very strong tool for helping people stick to a significant caloric deficit. So the caloric deficit with or without the aid [01:05:00] of these GLP one agonists seems to be certainly the best way to drive a deficit, but there are some additional benefits of having a high activity level along the way, whether it's in terms of maintaining muscle mass or getting some boost in energy expenditure, even if it's not quite as large as you'd predict based on the calculations in a, as a CSM handbook.
Yeah. It still counts being high, but not as high as we thought. And also there's some research really intriguing stuff related to the capacity for some amount of exercise to help with appetite regulation. So for whatever reason the exact mechanism still really eludes me when I try to think through it critically.
But there, there is a non-negligible body of evidence to suggest that. Going from very inactive to moderately active seems to really cut down on hedonic eating. So just,
Dr Mike T Nelson: yeah,
Dr Eric Trexler: overeating for the pleasure of how good it feels to eat. Yeah. Which by the way, another cool [01:06:00] thing that Herman published within the last couple years that whole idea of like humans when we're not very active, we tend to overeat a little bit.
It just is how it is. That's not a uniquely human thing. That also seems to be a primate thing. So he did a really cool study where he compared like, very sedentary a adult humans in industrialized nations to. Hunter-gatherers who have fewer caloric resources and are on their, they're, it's not unusual for a hunter gatherer to walk 20, 25, 30,000 steps a day versus, a sedentary American at like 6,000.
Right. So that was the human comparison. But also he looked at a variety of different primates. I think it was close to two dozen different species, ranging from like an orangutan to like a mouse lemur, and everything in between. But basically looking at doing a comparison of.
This species in the wild compared to this species in like a cushy animal sanctuary or zoo, where it's basically like you got no predators, you're not [01:07:00] running for your life every day. You don't have to go forage, long distances. All the food is brought to you in a beautiful little silver tray.
It's always, the freshest fruit or whatever you like to eat. And basically the obesity or the magnitude of excess adiposity that is developed in primates who are just living the cushy life is actually very much on par with what we see when we compare sedentary, generally overfed populations to populations who are, like I said, they're on their feet, 25,000 steps a day when they want food, they gotta go hunt or forage.
And the caloric resources, there are low physical activity levels are high. So. It does seem to be that if you're a primate and you're living the good life, we do tend to overeat a little bit. But for whatever reason like I said, it seems like being at least moderately active seems to cut down on some of that excess hedonic eating that is actually driven by more, seeking of pleasure and comfort more so than pure like physiological [01:08:00] hunger.
Dr Mike T Nelson: Yeah. And I think a lot of that just comes down to state management too. Like you're relying on a biochemical solution and you should probably lean on somewhat of a biomechanical solution, some movement and things of that nature. But again, does that, it's like what we talked about, that's not a linear scale either.
Right? Right. It's gonna break down probably at both ends of the spectrum.
Dr Eric Trexler: Oh, yeah. And we also see like, and that's, man, well, like you said earlier, it's so. Comforting to think in linear terms. Like, oh, how it's so much, much easier. That's how the human mind likes to operate. But yeah, so we see, just like we talked about, how energy expenditure versus activity that it starts to, get very non-linear.
This relationship between, activity level and energy consumption. At first, there's this excess energy consumption due to hedonic eating mostly, and then you get more active in that hedonic eating comes back down and we see energy intake dropping, but then you start going from moderately [01:09:00] active to extremely active, and then we see energy intake spike back up again because now there's actually a physiological reason.
To be over, to be eating those extra calories and actually replacing what's being lost by this high activity level. So yeah, it ends up being this extremely non-linear relationship and something that is worth noting. Mike, I don't know if you've ever dug into the literature about the relationship between, physical activity and exercise and.
Energy intake or hunger responses. But it's a mess, man. Like, no,
Dr Mike T Nelson: it's a mixed bag of, I can't figure out shit.
Dr Eric Trexler: When you talk about like, like actual exercise intervention, so structured intentional exercise interventions, you can go find five of 'em that say, oh, this intervention, attenuated hunger, and then five more, so these people could not stop eating after they did this intervention.
And then one study that says half of our people stopped eating the other half gained 10 pounds. And it's, I'm exaggerating a little bit, but it's a complete mixed bag. You're not that
Dr Mike T Nelson: far off from what I've
Dr Eric Trexler: seen. And yeah it's really chaotic. And so I think we [01:10:00] need, we still have a lot of work to do to digging into what are the factors that causes response A versus B eating way more versus eating way less.
Certainly I think it goes without saying that timescale and intensity are big drivers of that variability. Yeah. So if the workout feels intense to you. And we're looking at short timescales of energy intake. Think about it. You go do a just brutal workout of 200 meter sprints on a track on a hot day, and then you come in, do you want to have a big old, Turkey meal?
Like no, of course. Like you're just like, I want some water, maybe some Gatorade. I can't even think about eating. I'm still nauseous from that workout. So clearly, the timescale is a major confounding factor that makes this research look so messy and chaotic. Certainly the intensity relative to that person's fitness level is gonna be a major modifying factor.
But even with those in mind, you start digging through that research and you're just like, man, this is really hard to sort through. So I expect we'll learn more about that over the [01:11:00] next 10 or 15 years, but it's gonna take some time.
Dr Mike T Nelson: Yeah, and I've noticed that in practice, like I may have, some people do super high intensity stuff.
Most people will not feel like eating right after it. Some people could just not eat the rest of the day and it doesn't like literally bother 'em at all. Some people get stupid hungry like two, three-ish hours after. And I've even tried, making an UPS same percentage of their capacity in their VO two max and, trying to normalize the output.
And I don't know, like, I still find it, I can't figure out why that happens in one person and not the other person.
Dr Eric Trexler: Yeah, it's like so many things related to weight management and appetite regulation, probably we're gonna find that there is some kind of quantifiably distinct response that's happening that involves, something in the hypothalamus neighborhood, right? Sure. It's gonna be probably a very neurochemically mediated thing in terms of the response to, to exercise that. That's always if [01:12:00] that is your default guess on matters related to weight regulation, you're gonna do better. Probably pretty
GMT20251017-165833_Recording_640x360: close.
Dr Eric Trexler: Yeah. You're gonna do better than anybody else. So I do think eventually we'll get to the bottom of that, but for now this is one of those areas and when possible, I, I try to lean on research to, to guide the way, but this is one of those areas where I'd say, well, because of leaning on research, I can tell you that I have no idea how you're gonna, how you're gonna respond to this in terms of appetite.
And so I think it's really important if you work with people or you're managing your own training. You got to, frankly just pilot that and see what you get. You may find that the right balance of increasing your energy expenditure and not having this disproportionate hunger response, maybe it ends up being lower intensity stuff maybe ends up being higher intensity stuff.
I think more often than not, the higher intensity stuff seems to work a little better for many people than the lower intensity stuff in terms of that kind of chronic elevation of appetite. But that's one that I think you gotta experiment with and play it by ear. And if you're [01:13:00] a coach, I would implore you do not let that be one of the areas where you get really stubborn and set in your ways and say, no, I know how people are supposed to respond to this.
Because at that point, you are completely outta step with the literature as it currently stands. We do not have this kind of unified, very clear response of do this much exercise. Here's how your appetite will respond. It seems to be highly variable.
Dr Mike T Nelson: Yeah, because I've posted some stuff in the past as we wrap up.
That was high output, high, like true high intensity interval training. And it was a person whose main goal was body comp. And more than a few emails I got from people were, oh my God, what are you doing? You stupid nerd. Don't, everyone gets super hungry after this. You're just increasing their appetite and you didn't really burn that many calories for it.
And I'm like, but this person didn't overeat after it. I could show you someone else who did, who we did some of that, but it was controlled [01:14:00] because of that. And that's, and again, that's like I could go find five studies that say yes, five studies that say no,
Dr Eric Trexler: yeah, no it's a vexing problem.
And yeah, there will be no, no shortage of research on that in the coming years, I think.
Dr Mike T Nelson: Yeah. My last little axiom is, what do you think about this? That. In general, my simple story I would try to sell would be, do exercise primarily for adaptations, whether that's lifting or cardiovascular. Your goal should be to get the adaptation of that thing in the best scenario, and then use your neat or walking as a way to titrate movement with the overall assumption that your goal is more on the body composition side, and then obviously control your calories.
Dr Eric Trexler: Yeah, I think that's very fair. I think that's a very practical approach. And, I ended up writing the chapter on cardio for nasa made a certification for like [01:15:00] bodybuilding and physique coaches.
Dr Mike T Nelson: Yeah, I heard about that. Was it Dr. Guillermo was helping with that too, I think.
Dr Eric Trexler: I believe so.
Yeah, I believe so. Yeah. So I, I wrote the chapter on cardio and that ultimately was the main thrust of it was I was like, you know what? If you're a bodybuilder in theory you're not, cardiovascular adaptations are probably not high on your list. So I basically said, in the off season or early in prep, you're just doing enough cardio to make you feel good about your general health.
So maybe that's just going for a walk. Maybe there's some cycling or jogging in the mix. But for most people, that's gonna be pretty simple stuff. And I pretty much advocated in that again, because those, kind of athletic adaptations aren't really a high priority, you probably want to delay reaching, deep into the cardio drawer metaphorically for as long as you can.
And to the extent that you can such that in your bodybuilding prep, maybe you get through the whole thing and you don't need to do any structured cardio. Beautiful. [01:16:00] I've done that before. I've heard of other people who do that before. But yeah, it's the same kind of premise, which is I want you to maintain a high activity level mostly by just being a physically active person.
Be on your feet more, do more things that involve walking rather than sitting. If we need to dip in to do, more substantial cardio for a targeted reason, then we will. But yeah, for the body composition element of it, definitely the two big pillars are lift weights be generally active and some people will need to layer some cardio on top of that.
But I, in my view, you probably want to be pretty sparse with that unless there's a specific adaptation that you're adamant about achieving, then you do your cardio to the level of adaptation that you want.
Dr Mike T Nelson: Yeah, and that's why I make an argument for if you have the VO two max of a field mouse, like you're probably not gonna accumulate enough volume lifting unless you've got.
Oodles of time to make it worthwhile.
Dr Eric Trexler: Yeah.
Dr Mike T Nelson: [01:17:00] But that's getting into kind of more of the weeds of it. And if you're a bodybuilder, do you need a VO two maxxi 60? Hell no. That's probably way, that's like taking a sledgehammer to kill a mosquito, yeah. And again it's back to what are your rate limiters, what do you need to do to fix the rate limiter on an individual basis?
That type of thing.
Dr Eric Trexler: Yeah. And I know it's challenging 'cause a lot of people you know, right now are really into kind of a maximalist approach to VO two max. Oh yeah.
Dr Mike T Nelson: Well, VO two max is the be all thing. And trust me, I put out a lot of stuff on VO two max. I think it's important.
Dr Eric Trexler: Yeah.
Dr Mike T Nelson: But it has to be within the context of who you're working for, what you're doing that kind of stuff
Dr Eric Trexler: too.
Yeah. Yeah. So you, I, you will encounter some people who are like, okay, my main thing I'm interested in is bodybuilding, but I did hear that if I wanna live long, I should get my VO two max to like 71. 71. It's like good luck, so go become a pro cross country skier and then also be a body boat.
No but I definitely I think it because, and because people make very good content pointing out how [01:18:00] important VO two max is. There's no disputing that.
Dr Mike T Nelson: Yeah.
Dr Eric Trexler: But it does I think a lot of people struggle with the compromises that come with chasing this goal or that goal. And if they're both very ambitious and they maybe pull you in two different directions in terms of your training, programming or the body weight that you wanna maintain, I think people run into a lot of confusion with that and feel like they're stuck.
So but like you said, like if your goal is to be a person in generally good health, maybe not the like epitome, like the poster child of optimal cardiovascular health, but if you just wanna be a reasonably healthy person and have your metrics in those ranges that say kill cool. You get a thumbs up.
Like you said, I, I remember. When you do an exercise physiology degree, they're gonna get you on the treadmill. They're gonna make you, they're gonna make you do a VO two max test. And I was really pleasantly surprised the first time I did it, I was in bodybuilding mode had relatively low body fat, relatively high muscularity.
I was an active person who didn't do cardio, but did walk around a campus all day. [01:19:00] And I was very content with my note, I think it ended up being high fifties. And I was like, great.
Dr Mike T Nelson: Oh, that's great.
Dr Eric Trexler: Yeah. I was like, that's
Dr Mike T Nelson: great. I
Dr Eric Trexler: was pleasantly surprised. It was mid fifties.
Dr Mike T Nelson: That's
Dr Eric Trexler: too
Dr Mike T Nelson: good.
Dr Eric Trexler: But no, I was very happy with it. Yeah. I was like, oh my God, this is great. So, but yeah, it's important to like, set expectations that it's like, yeah, like that's, if you are lifting a lot, very active, maintain a low body fat, high level of muscularity, your relative vo O2 max will probably end up being in a pretty solid range.
Yeah. But if you're trying to like, maximize it, then you're gonna have to start, you're gonna have to layer. A substantial amount of structured cardio in, if you have any goal that is remotely approximating the highest vo O2 max I can get. Right. It's just part of the deal.
Dr Mike T Nelson: Yeah. And then it's back to, it's a nonlinear output.
Like if someone is training and let's say their VO two max is 30 and they come to me and they want to get to 40 and they're not doing a lot of cardiovascular work, that's not too bad. 40 to 50. Okay. Yeah. We might do a little more [01:20:00] dedicated stuff. 50 to 60. Oh man, I don't know. You're in my opinion, you're got that break point of the curve where you're gonna have to do some very high dedicated work and probably give up something else to get to that point.
So you're back to these non-linear trade-offs you have to make along the way.
Dr Eric Trexler: Yeah. And of course there is a big heritable component, right. So,
Dr Mike T Nelson: oh, it's a huge genetic
Dr Eric Trexler: component. Yeah. So
Dr Mike T Nelson: massive.
Dr Eric Trexler: I I don't want my anecdote to seem like counter-evidence to the ranges you just gave. It's. I think I'm born to be an endurance athlete.
Mm-hmm. It's always, even though I don't find it remotely fun or interesting or engaging, every time I've dabbled in things that are endurance oriented, it just, it's way easier for me than anything strength, power oriented. So I'm definitely unusual in the idea. And I also, at the time I had like legitimately like 7% body fat, right?
Yeah. So there's always gonna be a muscularity component, a total body weight component, and then can you walk uphill for the Bruce protocol long [01:21:00] enough to hate yourself? But yeah the numbers you mentioned are completely in line with the evidence and yeah, it's, if you want to, like you said, make that jump from 50 to 60, you're pretty much gonna look like an endurance athlete at that point.
Dr Mike T Nelson: Yeah. Yeah. Awesome, man. Well, thank you so much for all the time. Where can people find out more about you? All the stuff you got going on? I know you've got stuff on the social media, you've got masks, you've got podcasts, so tell us all about it.
Dr Eric Trexler: Yeah. Well the big thing, obviously, as always, is the mass research review over@massresearchreview.com.
We review new studies every month related to exercise, nutrition, and all sorts of related subfields. In support of that, I, we do a couple podcasts. So I co-host Iron Culture, the podcast with Eric Helms. I also co-host a newer podcast with Lauren Colenzo Simple, which is called Front Page Fitness, which is more topical, timely stuff that's in the headlines.
And then if you wanna look out for me personally, you can find me on Instagram at Drexler Fitness.
Dr Mike T Nelson: Awesome. [01:22:00] Well, thank you so much. I really appreciate it. This was great. And good to chat with you again.
Dr Eric Trexler: Yeah. Appreciate it. Take care.
Dr Mike T Nelson: Thank you. And Cool.
Speaker 3: Thank you so much for listening to the podcast today. Really appreciate it. Huge thanks to Dr. Eric Drexler for coming on the podcast and having a great discussion. As always. I always learn new stuff chatting with him, and I'm sure you did too. And our affiliates that I use. Yeah. And these are all devices I use.
Check out our friends over at Element if you're looking to change your nervous system. Check out our friends over at Shift Wave. Uh, they just posted a cool little story about the San Jose Sharks using some of their devices after NHL games to help down-regulate in the evening, which if you have to train late or you've got a goofy schedule or you're a professional athlete [01:23:00] and like the NHL, a lot of times you have to perform games late in the evening.
One of the real issues with those athletes and even other people who work in different professions is. It's hard to down-regulate at night. And so the shift wave I found is super amazing for that. Sometimes I've had to do late night, uh, training and allows me to down-regulate, uh, much better. And again, it's using basically pulse pressure waves to do it.
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Speaker 4: There's something wrong with his hearing aid. Yeah. What's wrong? I can't hear with it.
Speaker 5: Oh, no wonder. It's too far away.
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