The Peter Attia Drive - #291 ‒ The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more | Derek, More Plates More Dates Pt.2

Episode Date: February 26, 2024

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Derek is a fitness educator, the entrepreneur behind More Plates More Dates, and an expert in exogenous molecules commonly used and misused by bodybuilders and athletes. In this episode, Derek returns to the podcast to explore the impact of exogenous molecules on male and female health. He covers testosterone, DHT, DHEA, progesterone, clomiphene (Clomid), hCG, and various peptides, alongside updates from the FDA affecting peptide use. Additionally, he addresses the recent hype around increasing muscle mass through myostatin inhibition via follistatin gene therapy and supplementation. Additionally, Derek discusses the various strategies that bodybuilders use for losing fat while preserving muscle, including insights on weight loss drugs. We discuss: Testosterone and DHT: mechanisms of action, regulation of muscle growth, and influence on male and female characteristics [2:15]; TRT in women: the complexities and potential risks associated with testosterone use in women [9:00]; DHEA supplementation: exploring the benefits and risks for women, and the differing effects on men vs. women [22:00]; The role of progesterone in both men and women, pros and cons of supplementation, the importance of tailored doses, and more [28:00]; Measuring levels of free testosterone [37:15]; The trend towards earlier interest in TRT, and the risks of underground sources of testosterone [42:00]; The complexities and considerations surrounding the use of Clomid, E-Clomid, and hCG in TRT [46:00]; Low testosterone: diagnosis, potential causes, treatment options, and other considerations [53:45]; Growth hormone-releasing peptides: rationale and implications of the recent FDA categorization as high-risk substances [1:03:45]; Follistatin gene therapy and myostatin inhibition for increasing muscle mass: the recent hype online, human and animal data, and the need for more research [1:14:45]; Simple tips for lowering calorie intake and losing fat [1:32:30]; Methods of sustainable fat loss with muscle preservation: insights gleaned from bodybuilders [1:40:00]; Could prolonged fasting impact testosterone levels? [1:55:30]; High-protein ice cream [1:57:00]; Exploring fat loss supplements and drugs: L-carnitine, yohimbine, and more [2:02:15]; Potential remedies for individuals experiencing metabolic dysfunction due to hypercortisolemia [2:12:30]; The cornerstones of body composition improvement remain nutrition and exercise, even in the presence of exogenous testosterone [2:19:15]; The importance of approaching health advice found online with a critical eye and a healthy dose of skepticism [2:23:30]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Atia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free.

If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you want to learn more about the benefits of our premium membership, head over to peteratea.com. forward slash subscribe. My returning guest this week is Derek from More Plates, More Dates. Derek was a guest back on episode number 274, which aired in October of 2023. In that episode, we didn't cover nearly as much as I would have liked, so I wanted to

have Derek back for round two. In this conversation, we continue where we left off in our first discussion. We talk about a number of exogenous molecules that impact both male and female health, including testosterone, DHT, DHEA, progesterone, clomid, HCG, and various peptides. And we also talk about some updates from the FDA since our last conversation that impact the use of peptides. We also touch on myostatin, phallostatin, and more. We cover various ways that bodybuilders will lose fat and weight while maintaining muscle,

including the various weight loss drugs that are available. As a reminder, Derek is a fitness educator and entrepreneur behind the More Plates, More Dates YouTube channel, podcast, and companion website. So without further delay, please enjoy my conversation with Derek from More Plates, More Dates. Derek, good to see you again. Thanks for having me again, Peter. I appreciate it.

Yeah. So last time we spoke, we covered a lot of ground, and yet somehow at the end of it, we felt like there was still a lot to talk about, so hence we're back. And I'm gonna do something unusual, which is I'm just gonna tell you, hey, what do you wanna talk about,

as opposed to driving down my agenda? I have a bunch of things that I wanna talk about, but curious as to where you think we should pick things up. Yeah, I think that a lot of stuff we covered at a surface level, and maybe there might be some unanswered questions or ambiguity on some specifics when it comes to am I a good candidate for hormone replacement? How would I assess that? Should I be worried before I get on it? What kind of thing should I look for? I feel like getting clear on that might be worthwhile because a lot

of people are kind of in that boat where they don't know who to trust, they don't know who to listen to, and I know even yourself, you're kind of like teetering on the thought of maybe exploring it. So I feel like even seeing what your thought process is going into evaluating is it viable for you would be super valuable. Yeah. So let's maybe back up a little bit and give folks a quick primer on the topic. So let's just start by just talking about Testosterone. I don't know if it's just that I'm more attentive to it or there's truly been an increase in marketing efforts, but it really seems like the last decade and presumably it's also just

the explosion of social media and more channels through which this information comes at you. But clearly there's been a lot more attention about forth to this idea. And it's very interesting because there's historically been kind of a negative connotation associated with testosterone, natural hormone, we can talk all about that. But of course, its role as a drug of abuse in sports has sort of tarnished it in a way that we don't see on the female side. So when we talk about hormone replacement for women with estrogen and progesterone, that doesn't come with the same performance enhancing benefits. Which is odd, eh? It's viewed as such a taboo thing even though at the end of the day it is just a natural

hormone that you produce. Right. And so it's interesting, of course, that estrogen and progesterone are not scheduled drugs. They're hormones. You prescribe them without any limitation. They're unscheduled by the DEA. Conversely, testosterone is scheduled and much more highly regulated. And again, the suggestion here is that there's potential for abuse that we presumably don't see with estrogen and progesterone. That's neither here nor there. It just is what it is.

So maybe let's just talk really briefly about testosterone, androgen receptors, how they work, the role of DHT, and what this does for muscle protein synthesis. Maybe just a kind of quick background on that. Yeah. So in general, most people are aware of testosterone as the primary masculine hormone, but in reality it's produced in significant quantities in both genders, just proportionally more so in men to the magnitude of 10x that of females I believe. And also both men and women produce estradiol and DHT as well.

They just have differing proportions and binding proteins and whatnot. But at the end of the day, the action in the body is the exact same. It still binds to the androgen receptor, induces gene expression and causes muscle protein synthesis and other anabolic actions in bone, psychoactive effects in the brain, etc. And just the magnitude to which it happens differs between Texas and it also is what essentially determines how you sexually mature and differentiate as you enter adolescence. So you could realistically manually manipulate it too. And you see this in sport, doping scenarios,

bodybuilding males, you see it all the time. So ultimately, this is the primary androgen that dictates muscle growth and anabolic activity in tissues and the metabolites of it regulate a bunch of other things in the body which we could get into. But to keep it like high level simple, it is the main primary androgen that men and women alike rely on just that differing amount. I can't remember if you and I talked about it on our previous podcast. I know it's been discussed on the podcast. We'll link to it in the show notes where I go into great detail mechanistically about what happens when testosterone binds

to the androgen receptor and how that gets into the nucleus and how that impacts gene transcription into translation for protein. What's interesting, of course, is that you did mention DHT. DHT has a significantly higher affinity for the androgen receptor. Anything else you want to say about the role of DHT versus testosterone? Then we can just talk about it in one gender. We don't have to necessarily break it down. Yeah, so the spectrum of, I said androgen,

I didn't really elaborate what that even means. As far as I know, the definition is essentially to be male or to make male or something related to masculine characteristics ultimately is kind of what you derive from androgens and the further on this spectrum of androgenicity it goes the more masculine and viralizing potentially in women it could be. So DHT is that hormone essentially that drives this pathway to the extreme and is what is responsible alongside testosterone for maximal sexual differentiation, maturation in adolescence,

like I mentioned, but you see mutations in the gene that encodes for 5-alpha reductase, which is the enzyme that makes DHT. You'll note that certain pseudo hermaphrodites who don't have DHT will end up lesser developed in the masculine spectrum than normal functioning human with full DHT production. So this is kind of like an example of the spectrum of on one side, you have males producing 10 exatostostarone and more DHT subsequent to that. And then females, much more estrogen proportionally to males. Well somewhat depending on where they're at in their cycle and whatnot. And then 10x lower this testosterone and also much less Dht and this ratio of androgens

to estrogen essentially is what dictates are you going to have male characteristics or female characteristics and how much are those characteristics going to get exaggerated because even if you're a full grown female, if you expose yourself manually to these hormones, you could very much push yourself in that direction. So DHT a lot of people know about it for its responsibility and what it does for hair loss, the common side effects associated with it, but it is an important hormone that does regulate how masculine you become as you grow up. So I think that's the best way to put it. And there's a critical window of exposure too. So embryologically, obviously, exposure to testosterone and DHT have an enormous impact on sexual differentiation later in life. I'll give you an example.

I have a patient, female patient, who's on testosterone and she accidentally for a period of about a month didn't read the directions correctly and was taking 10x the dose. And that's not that hard to mess up. It's very easy to do. This is something you have to be very careful with because the doses are so, so small. And there's no FDA approved women's testosterone as well. Right. You could have it compounded in theory at a lower concentration, but

regardless, she for about a month ended up taking 10x the dose, which means she was taking a male physiologic dose of testosterone. The symptoms immediately said, there's something going wrong here. The first symptom interesting that she noted, I would have expected hair growth to be the biggest issue. It was clitoral enlargement within just a period of a month. The good news is completely reversible once the dose was restored to the 10th that it should have been. I don't really follow bodybuilding closely enough, but I assume that female bodybuilders are routinely using doses of that nature? Yeah, they are depending on their guidance somewhat or very aware of the

masculinizing potential of what they're using, and some will avoid testosterone entirely because of that, because it is essentially equal anabolic as it is androgenic. So it begs the question, why would you be using testosterone as a female if you're trying to achieve super physiologic muscle growth? You kind of know in order to push it to that extent, you're probably going to end up in male characteristics territory. So oftentimes they will defer to compounds like oxandrolone, which is anivar. They'll use things like primabolin sometimes, metenolone. So meaning much more anabolic, much less androgenic.

Yeah. So these are synthetic compounds that have been manipulated to be more tissue selective as in more anabolic activity relative to the male viralizing component. Unfortunately, you can't segregate the two entirely, but they do what they can. And the best thing they can do is keep an eye on the side effects as they manifest in very, very real time, keeping a close eye on it. I know some women who even have a decibel voice recorder, and they will monitor

if their tone is getting lower or not. Is that potentially an irreversible change if voice is changing? Yeah, so you have to be super careful especially. Even in TRT, if you were going to do TRT as a female, a lot of the clinics nowadays will advertise and market testosterone in a way that is highlighting how great it is for libido, quality of life, glucose management, muscle growth. Like there's a lot of things that sound attractive about it that are an easy sell to a female who may be asexual and like perimenopause or something. And I've seen standards being promoted as cookie cutter. Everyone should have a 200 nanogram test leader total test, which is crazy.

Wow, that's very high. Yeah. So my mom actually got on hormone replacement a few years back. And I at the time wasn't overseeing, didn't really check what she was doing exactly. I just kind of trusted that the guy who was prescribing, he was very experienced and credentialed and seemed like somebody who I would go to myself to ask for a verification. Is this like a protocol? It makes sense. And within just a couple of weeks, pick up the phone and I almost don't even

recognize her. I'm like, what mom? It's skewing in the direction of male blatantly, but she couldn't really tell. And what dose was she on? I don't remember exactly what the dose was because it was like a cream and the compounding creams can vary, like you said. But whatever it was, it was one of the practitioners that promotes 200 to 300 total tests in females, which is insane.

Well, maybe we're talking about that for a second. I mean, we'll go back and talk more about TRT, but while we're on the topic, as you alluded to earlier, there is no FDA approval for testosterone in the use of women. So there is for men, of course, and there's obviously an FDA approval for estrogen and progesterone in the use of women. The thinking with testosterone is that when a woman enters perimenopause, not only does she experience the predictable drop in estrogen and progesterone, but with it, so too, goes testosterone.

And, of course, the rationale is that testosterone is still a very important hormone in women. I've pointed this out many times before, but the units that are used to represent estrogen and testosterone are very misleading because they're not the same. So if you convert them to the same units, you will see that even in a woman, her testosterone is significantly higher than her progesterone and estrogen. So if you took a mid-follicular estrogen level, an estradiol level, and took it out of picagrams per deciliter and put everything in nanograms per deciliter.

Her testosterone as a premenopausal woman would be at least 10 and at times even 50 times higher. So the idea is, well, clearly losing a hormone that's that abundant must have ramifications. There are, you've alluded to all the side effects. And so the thinking is, well, we should replace it. And the question is to what? Now, I've never heard a compelling case for why it should be replaced to a level that exceeds her physiologic limit in her 30s, for example. And I've never seen a woman in her 30s with a total testosterone between two and 300 nanograms per deciliter. In other words, those levels exceed even her peak physiologic level. So it doesn't surprise me that that would be androgenizing women. Do you understand or do you have a sense from these folks doing this what their rationale is for going so high?

I think their idea is simply that this is where we achieve blatant symptom relief in everyone and a feeling of optimization above and beyond. Like this is what it should feel like when you take hormone replacement. And I think it's just creating a state of ultimately androgens feel pretty good if you were just crashed or very low. And then all of a sudden you're essentially on the male proportional equivalent of like a bodybuilder cycle or something.

So I couldn't say why they do it exactly, but all I know is it's too high and it's very common to have some of these like viralizing outcomes. And if you're not keeping a close eye on them, they can really, really snowball. Cause when you're seeing keeping a close eye on them, they can really snowball because when you're seeing yourself in the mirror every day and you're listening to yourself, you don't really notice these little minute changes as much as somebody else, then you might meet up with a

friend a month later and they're like, what the hell? You don't even sound the same. Yeah. The other thing that amazes me is there's another symptom that is so common even at physiologic doses for women who are sensitive enough because a lot of times you're treating a woman and let's say she's 45 and she comes to you and she has almost unmeasurable levels of testosterone. So she's sort of in the 10 to 20 nanogram per deciliter level. Now you didn't know her when she was 30. So you don't actually know what she was when she was 30. People weren't measuring her testosterone 15 years earlier. But you say, look, we're going to set a target of 80 to 100 nanograms per deciliter, which

is sort of in the ballpark of what would be kind of 70th to 80th percentile for women that age. But then it turns out that she probably was lower than that because once you get her acne is out of control. You would surmise from that that, well, she must have lived at a lower level and for her, Aidae is super physiologic. And it's for that reason that I just can't imagine that they're pushing women to 200 and 300 who are not developing horrible cystic acne and facial hair. Some of them like how much they feel so much. And now I'm having sex multiple times a day

even with my husband who I didn't even want to touch right a couple months ago. So it's a pretty big shift and if they like what they're getting out of it sometimes compromises will be made in order to continue with what they think they need to be taking to achieve that feeling. And in addition to that too, like you said with the not knowing where you were at further confounding that is how many people have been on combina roll contraceptives for like decades. Yeah, just totally skews everything. Yeah, like I've dated girls who I've seen like 80% suppression of their hormone levels.

testosterone, free testosterone, especially proportionally more so too because of the rise in the SHBG goes through the roof. That's ruthless. So they're like operating in a state of androgen deficiency perpetually and relying on this synthetic progestin to drive all testosterone-like behavior essentially. And then if they get off, they don't even know what their natural is. Like they've never experienced it because they've been prescribed it since 15 years old or 16 years old or something.

So it's tough because it's like, you don't even know what your ideal target is. Even if you were getting blood work oftentimes, it's totally skewed. And that's something I definitely want to talk about on my podcast too, is some of the testosterone suppression in different formats of birth control. Because it's pretty nebulous, some of it. Like I'm very aware of the combined oral contraceptive data, but even like the localized progestins and stuff. There's like very minimal literature, shockingly. Like if I'm trying to find out how much the marina affects my girlfriend, I don't even know.

I don't know what her baseline probably was. Have you been following at all the Natesto product? Looks good if you're willing to tolerate it. Yeah. For folks who don't know, Nattesto is an intranasal administration of testosterone and I believe the dose is like 7 milligrams and it's used TID so three times a day which tells you that obviously the bioavailability is quite low if you're taking 21 milligrams daily. So that's slightly more than you would probably take if you were just

doing it intramuscularly. But nevertheless, the idea with it is it's quicker acting. And that's why you have to take it sort of three times a day because it's not sticking around like in a fat depot, the way an injectable source would be. But the interesting question is, does this help address some of the female use case? So for example, if one of the symptoms that a female is turning to testosterone for is libido, does she really need to be on mega doses of systemic testosterone around the clock versus in the same way a man would use C. Alice for an on-demand ED issue? Could a woman be using intranasal testosterone for an on-demand libido issue? I would hope that'd be the case. In practical application, I don't know if it plays out

that way where you could just acutely use it once a week or something on the day you're wanting to get busy. I've candidly had some experimentation with it and doesn't seem to make at least that big of a difference. With you or with a female? No, with a female with like a low testosterone. Because I was going to say in a male I wouldn't expect it to have that effect. No, I would make no difference in a male. Yeah, yeah, yeah. But you're saying in a female with low testosterone taking a couple of shots of

Natesto didn't in the subsequent hours have much of an impact on libido? No, but that's obviously N of 1. I haven't actually seen the data in literature myself. I don't even know if it exists right now. I'm not aware, but I believe there is a clinical trial ongoing. I think it might be happening at Baylor, but I'm not sure. And one thing I can say is, as much as it sounds great, typically women don't like using it that much. Just because it's messy and...

Yeah, it's like dripping down the back of their throat. It's invasive in a way that's not very clean. You just feel kind of gross. Feel like a drug addict almost, like snorting some shit before you go have sex every time. Yeah, interesting. Obviously the not having sex and not having a libido, probably a worse outcome for many of them.

So if it works in the short term on like a use by use basis, I'm sure it's individual case dependent and I'm sure you could double up the dose and maybe get more of a bang for your buck effect. I'm just like skeptical that anyone's going to use it more for novelty once in a while. And then I don't know. Interesting. I've never actually seen the product. I don't know what the viscosity of it is.

I don't know what the user experience is like. Is it particularly viscous or is it kind of like a nasal spray that you would use for, you know, an anti-histamine or something? The one I had experience with was a compounded replica of that. So maybe the Natesto formula itself is actually more tolerable. So I probably should have prefaced with that. But the compounded variant that I tried that was replicating that product was not that pleasant. And it was like almost like creamy, not a spray. I would want to see what the real deal product was like. Let's talk for a moment about DHEA. So that's the other

thing that seems to be all the rave today. A lot of my female patients are asking to be put on DHEA. And I'm not sure where this came from because DHEA has been around forever. It's one of the few hormones that's available over the counter. That's a relatively unique situation to the United States. Not in Canada though. Don't bring it back to Canada or else you get it. That's my point. Yeah.

So even across the border with our neighbors that were otherwise pretty similar to DHEA is. Yeah. Schedule one. Yeah. If you have that, you're doing something more illegal than having anabolic steroids. Wow. I did not know it was schedule one. And yet here it is going to Amazon and you can fill your boots with it. Yeah. Which makes no sense. No, it makes no sense until you understand there's a dirty political story as to why

that's the case. There's some really backwards compound selections though that are banned. Like for example, you can buy a Fedron in GNC in Canada. It's like, why? It's literally used to make meth. And then here, it's a lot harder to get a Fedron. But then you can get Yo-Him buying here, which is a fat burner we'll talk about later. And in Canada, it's banned. Who's selecting what gets banned? So a lot of women,

for some reason, have recently, like in the past few months, been sort of saying, I want to be on DHA, I want to be on DHAA, I want to be on DHEA. And there's somehow being led to believe this is the elixir of life. I'm sort of trying to scratch my head and understand why they're saying that. Presumably, they're saying if my DHEA levels are low, it could explain my low testosterone. And this is a quote unquote more natural way to increase my testosterone. I haven't seen any compelling data that DHEA does much of anything. What did the data say? I looked in a decade, by the way. So a decade ago, when I was really beginning to get interested in hormone tinkering,

I came to the conclusion DHEA didn't do much. Yeah, if you look in males, you will find no utility. It has no effect on testosterone. At best, you get a spike in estrogen and no testosterone seemingly through, you know, whatever backdoor. And yet it's a USADA water banned drug. It's treated just as testosterone would be or any other which is wild. But in females, it actually is useful and can increase testosterone to the degree that if you had, and this is a pretty wild study that I haven't really seen anyone

talk about, I'm sure somebody has, but a few years ago I was looking into for the very reason of my girlfriend at the time was shut down to nothingness on a combined oral contraceptive. And I'm like, what can you do in this situation? And I found some papers that showed using DHEA supplementation exogenously. How much? 25 a day? 50. 50 a day, okay. And a full restoration of total and free test levels

while still using your combined roll contraceptive. To me, that's pretty damn impressive for something that's not a cream you have to apply, spray you have to put up your nose. And this thing reliably depending on, cause again, combined roll contraceptives, there's many different variants you could get. So depending on the brand, you might oral contraceptives, there's many different variants you could get. So depending on the brand, you might have a progestin that's more androgenic

or one that's less, ethanol astrodial is or isn't included, that will all vary. But in general, in like the traditional, most sold and prescribed combined oral contraceptives, it was restoring total test levels to that of baseline while staying on what is otherwise a brutally suppressive compound. And give a sense of what the increase was from what to what was total T. Oh, it was like going from your natural 60 down to like 15 back up to 60. Okay. So 4x bump in total T. This was only in women on an OC? Yeah, there's probably data on just not on anything, but I don't recall at the top of my head.

So why do you think women would be more sensitive to this? Probably because a significant amount of their androgen synthesis derives from adrenal hormone production as opposed to men. It's like if you castrate a guy, you can still squeak out 30 to 40 nanograms per deciliter from his adrenals. Yeah. And in females, it seems to be similar depending on the woman, you know, proportionally, but 30 to 40 out of her adrenals could be three quarters of her total testosterone. Exactly. So for men, it's like a drop in the bucket. But for girls, it's like maybe three quarters of the bucket. I'm going to check that

paper out. But that might be a nice thing to have in your pocket if you live in the United States. One thing I can say though is DHEA in women who have natural levels that look pretty good, like let's just say you're on hormone replacement as is. And then you think you need DHEA for some subjective feeling or well-being. There's no real biomarkers to reinforce that you're deficient. Your DHEA looks normal. Your testosterone looks okay. And there's not really like a clear reason. You just kind of think you need it. Almost certainly the risk to reward is a little bit worse because acne on DHEA is very common in women to a degree where it's like the proportional upside you get out of it, you're not going to get as much

anabolic activity out of it relative to seemingly the androgenicity impact systemically or at least in skin from what I've seen. Remind me, we don't measure DHEA levels, we measure DHEA sulfate levels, correct? Yeah, that's the only proxy in like traditional blood work metrics that I'm aware of to test for it. Do you know why? I used to know why we couldn't measure DHEA directly in blood. I think the majority of it is sulfated, so getting a direct measurement is not as indicative of,

I don't know. The total body pool or what? Yeah, I wish I had a good explanation, but I just know that's the proxy. It's kind of like, why do we check IGF1 for GH? It's probably something similar. Okay. What about the role of progesterone? What do you think the role of progesterone is in both men and women outside of reproduction? So putting reproduction aside, one of the things that we're doing a lot more with our patients, we used to be pretty quick to abandon progesterone systemically. If women were having any mood symptoms associated with a full dose of it, and we would just very quickly adopt a morana, progesterone coated IUD to give the

endometrial counterbalance to the estradiol to prevent the hyperplasia and obviously reduce the risk of endometrial cancer with unopposed estrogen. But we're really seeing a lot of women in the middle ground who maybe can't tolerate a full 200 milligram dose of progesterone, which would be kind of the full dose, but feel great at 50 to 100. And so, in many ways, what we're trying to do is just find every woman's dose and what's the amount that you can tolerate. And if it's sufficient, great, if it's insufficient, we'll backstop it with a moraine. Why do you think that is?

Why do you think progesterone is so important for women? Outside of reproductive standard and utility, I think that it's more like if you look at a steroidogenesis cascade, which is like in layman's terms, I guess, if you took cholesterol and then all of the different things it could turn into when you cleave it and through enzymatic pathways turn it into glucocorticoids or like downstream to adrenal steroids and downstream to testosterone and DHT and estradiol and estrone and all that stuff. Like that is called steroid degenesis, the synthesis of all these steroid hormones in your body. And some of you guys might have seen this chart before and I'm sure you've showed it on the podcast. It's

like this big, messy thing that has like 7,000 different pathways. And it looks overwhelming, but up near the top where you start to have cortisol production, you have some of this stuff upstream for glucocorticoids as well as where pregnant alone branches from like to actual androgens and upward to like adrenal hormones. At the top you have this downstream cascade from progesterone that leads to an array of metabolite hormones that are pro anti-lytic as in they will be like anti-anxiety kind of balance out the sympathetic drive that you might get from androgens and also help you get to sleep.

So that's why progesterone is so useful at night and it's kind of why it's placed at that time for dosing as well. Taking it orderly also is like impactful on the way it's metabolized out to get some of these proportional metabolites too because if you had it in a cream or an injection not only maybe is it harder to get the dose you want out of it but the metabolite content that you get is totally different when you have a first pass metabolism versus you skip it. So with progesterone in particular, it produces an array of different things,

including but not limited to one is called allopregnant alone, which is seemingly implicated to some extent in post-phenasteride syndrome, but also very much in postpartum depression. And they've even created a synthetic analog of it now that they use to treat postpartum depression, which is interesting. But all of those different metabolites cumulatively, if you are deficient in some amount of them, depending on the individual's biochemistry and genetic predispositions, could result in like a more anxious human than otherwise.

So the dose required to balance out the androgenic signaling relative to all this other stuff going on, I would expect it would vary quite significantly female to female. And especially when you are backfilling hormones from a shut down state, It's not endogenously regulated the same way when you have feedback mechanisms. So you're kind of just manually shooting stuff at your liver and hoping it's gonna spit out the right amount of stuff. And you can only really do that through

some sort of titration slash experimentation and what dosages seem to produce repeatable outcomes in the literature we have available. So I would imagine a lot of women would have a dose dosages seem to produce repeatable outcomes in the literature we have available. So I would imagine a lot of women would have a dose that is far less to achieve the outcome they want or much higher or perhaps don't respond at all because it's not what they need depends but I think that would be my educated guess. Is there a role for progesterone use by men?

Yeah, so I said this last time and you seem baffled and it definitely does not have an approved use in men. There's no literature that points to it as this is something you should use in men or replace, but I do believe and see it play out where it could be useful to balance out some of that sympathetic drive and whatnot. You can look at blood work and kind of see, okay, in my like minimal negligible amount, should I be pushing that to the top of the negligible amount

that is my threshold? What doses do you see people using here? The same doses, like 50 to 200. That high. Yeah, yeah. And what are the side effects of that? So if you are not on exogenous hormones, it does have negative feedback. So

similarly to most people are very familiar with how estrogen has negative feedback to the hypothalamus pituitary ticular axis, antistosterone through androgen receptors, but what often goes overlooked is some of the other hormones like progesterone. So progesterone isn't as potent of a negative feedback regulator that I've seen, but it definitely is. And it seems to maybe even have antiandrogenic activity as well. And if it does that through competitive inhibition

or like I don't really know off the top of my head, I don't recall how it does it, but it does seem to produce antiandrogen like effects. And some of it may be mediated through the negative feedback and some of it may be inhibited through actual like transcriptional activity, but ultimately it's something that will lower your ability to have androgen like effects in the body to some extent.

But if you're on TRT... Doesn't matter because you're already shut down. Correct. So what would be the benefits when you're on TRT, doesn't matter because you're already shut down. Correct. So what would be the benefits when you're on TRT, what is it helping you balance out clinically? I think very common, we will see disproportionately high free androgen levels in men, especially when you look at, a lot of guys will look at their total testosterone,

their free testosterone, their SHBG, but what often goes overlooked is SHBG binds DHT with, I believe it's a five times higher affinity than testosterone, might be 10, I think it's five though, whatever it is, it's much higher. And that ratio of DHT to testosterone to estrogen that's freely circulating. Like you're regulating mechanism in the body, the primary one, because SHBG is like the main thing that determines how male you are essentially, well, besides the actual production of the hormones,

but DHT gets bound up with five times higher affinity than tests, which is like 20 times higher than estrogen. So if you have that regulatory framework, kind of like driven down through either a dose of testosterone that is higher than you need or like a super infrequent dosing pattern that results in like a disproportionate drop on certain days or an array of different things,

you could end up in this free androgen dominant environment where your sympathetic drive is kind of like keyed up perpetually. And because you have a long ester compound in your system, you don't have the luxury of indogenous manipulation of your hormones going up when you need them and down when you need them. Like the pulsatile framework of your natural production

is non-existent. You're just like getting a big spike whenever you inject and then it's slowly gonna diminish out of your system until you wanna inject again. And a lot of guys, even when they're doing, you know, twice a week or something, you're still getting like some level of spike and then dips and then spike and dips,

where if you were a natural with normal natural testosterone production, it would be like very pulsatile with a diurnal rhythm with natural dips and valleys and peaks and it would not fluctuate where it's like bam, bam. And if you look at a steroid plotter, you can kind of see how this looks and you want to compare a steroid plotter to your actual rhythm naturally. It's like not really the same. So that's kind of where you get into, you know, more frequent dosing might be better. But at the end of the day, a lot of people are overlooking how dominant the free androgen

profile could be in a guy on TRT, because you'll see your total testosterone, and it might be 700. When you measure it, but you're measuring it three days after your injection, you're looking only at free testosterone, your DHT has not been evaluated, your free DHT surely hasn't been evaluated. I don't necessarily think everyone has to spend hundreds of dollars to check those by the way, but just be aware that if your SHBG is lower than it was before you started TRT, there is a disproportionate regulating mechanism in play here now that you have to perhaps account for if you're in like a state of anxiety, like that might be a factor or if you have trouble getting to sleep, there's certain cues I would look to as to am I a little bit too redlined right

now? Given that free testosterone is typically estimated, I guess we can talk a little bit about testosterone measurements you were mentioning earlier that there's a direct way to measure free testosterone. I was unaware of that. Do you look at free androgen index where you're just taking the ratio of testosterone to SHBG? So you're taking the ratio of two things that are directly measured. Is that a better proxy for what's happening physiologically than this indirect calculation

of free testosterone? Which I mean, again, if my memory serves me correctly, free testosterone is a calculation based on testosterone, SHBG and albumin. Is there anything else that factors into it? Yeah, I'm pretty sure the free direct measurement via LabCorp is just based on those binding proteins. I don't think there's anything more to it, but with the equilibrium dialysis,

it is separating it and measuring it directly. And... Does LabCorp do the equilibrium dialysis, it is separating it and measuring it directly. And does lab core do an equilibrium dialysis? Yeah, it's just more cost prohibitive. So the good news is a lot of these tests, when they evaluate them against it as a gold standard track pretty closely with it, so you can use them as proxies that are relatively accurate. It does get skewed when you get into trying to measure hypogonadal men that might have, you need to be a bit more, I don't know, lower concentrations and you want to make sure you get it right. It's not just tracking trends as much or individuals who are using synthetic androgens, it will for sure cross detect if

you're using a immuno assay or a calculation Because it's gonna be based on the cross detection of the total testosterone presumably as well if you use that So in general if you wanted to use the gold standard, it would be equilibrium dialysis I don't know if it's always necessary however at baseline measurement for people who are trying to get as Ideal and accurate of blood work as possible. I would typically always go with the highest sensitivity and that's even with your blood work, it's not like it was wildly different on some of the metrics, but like it was significant

enough. Yeah, let's talk about that. So I wrote my values down. So for my last blood test, I did it, I had LabCorp run them both. I had them run the Immunoassay, which is not the gold standard. That's the cheaper test for both Testosterone and Estradiol and then the LCMS, which is the gold standard. And so here's the difference. So the enzyme-based Immunoassay for Testosterone was 502, but the LCMS was 381 so for people who want to know how to tell if the test is that one It says rosh eclia Right beside it. Yes, a roach is the company that provides the assay for them. That's like the only thing I think it says underneath it to identify. Yeah. Yeah, so that's a pretty big difference, right? I mean that's a 25 percent difference. I think it's significant enough to justify getting the accurate one.

Yeah. And that's the only one we do, but I just wanted to see what the difference was. So the accurate test read 381 to the inaccurate 502. Here's what's more telling was the estradiol. So the estradiol on the accurate test, the LCMS was 18.3 and on the enzyme-based test, it was 41.3. So that's more than a 2x difference. Yeah, the enzyme-based testing will cross-detect estrone synthetic astrogens as estradiol and it's annoying. I mean, that still seems really high, right? Given that my estrone, my estriol, they should be very low. I'm obviously not taking any synthetic estrogens. Why do you think it's off

by more than 2x? And by the way, I see this in other patients as well. That would be tough for me to speculate without seeing the full gamut. I think it's picking up something in my supplements. Like I think there's probably something else that's being detected. Now they say that probably. Yeah. I'm assuming you didn't take any biotin for ever taking biotin. Yeah. Okay.

You don't have any methylated B vitamins, bro. I do have methylated B vitamins. But biotin's not in your B complex. I don't think it is. Maybe it is in tiny amounts. I'm not taking a dedicated biotin. Put it that way. That would still mess with it.

Yeah, maybe. So maybe there's something in my methylated B complex. Stuff you should not take before your test. Last time we spoke, you said, we were both aware of biotin. And then you said, I'm not sure if there's other stuff that could affect it. I checked with Merikelth, which is my team,

they don't know of anything either. So I think biotin is the main thing. And I think it's skews, if I recall correctly, thyroid values pretty dramatically as well. So if you're taking a biotin supplement, it's worth noting you should stop it periodically before you take a blood test for, I would say, at least a few days, if not a week,

probably before your test, just in case. Got it. Okay, so let's now kind of shift over to the testosterone replacement decision-making in a mail. So it seems to me that younger and younger men are seeking out testosterone replacement therapy. Is there any data on that, or is that just sort of our perception?

No, you were right. As far as marketing efforts and exposure, if you look at just Google trends and you type in TRT, it's like the graph of how many searches are on Google is skyrocketed over the past decade. Where do most men get their TRT? How much of it is done from an endocrinologist, for example, like someone who presumably spent a lot of time understanding the system?

How much of it is done from clinics that only do testosterone as the other extreme example? Yeah, it's tough because countries will differ in their scrutiny on this stuff to such a varying degree that if I speak, I could speak to the US and give some sort of ballpark and I feel that's probably the most useful. And again, this is not based on some sort of survey or anything. This is just my speculation as to what I would imagine is happening from trends I've seen. Underground market is still the most easily accessible with the cheapest barrier to entry

and with the advent of internet e-commerce stores. It's not that difficult to find a website that sells testosterone or other anabolics and get some Bitcoin and buy it. So there's a lot of people that will get it from their Jimbros or online. It's very accessible now. The cost aside from the prescription barriers of finding a doctor who you actually think will give you the prescription and not necessarily knowing when you go into that consultation or whatever that they're going to be, you know, the flexible doctor that you need, it's just easier for a lot of guys to get it black market. So there's a significant amount of guys, at least in the fitness industry that are suppressed from their hormone use that will be on TRT underground. So I would say that

probably the majority of them are on not scripted TRT, even like lenient telemediclinx. I would say a majority are still using underground. Presumably crypto is what enables that because otherwise the DEA would shut these things down or is it too much of a game of whack-a-mole or there's too many of these around? Yeah, whack-a-mole. Yeah. So there's a lot that sell an amount of volume, presumably, that is not significant enough to focus on, or it's just like, it's so hard to track. Because even if you shut one down, another one pops up,

it's based in some country that's not even the US supposedly, and they drop ship it, and they use crypto, so it's harder to track the currency. Got it. And what kind of testosterone are these guys getting? Are they actually getting branded depotestosterone? Are they getting some knockoff from China? Often it's underground, but there are resellers of pharmaceutical grade too. And sometimes these guys will have connections with people in Europe, in certain countries where you can just walk into

a pharmacy and buy whatever you want for one tenth of the price. And then they will mark it up and then sell it to you in the US. And yeah, so there's an array of different options, but typically it is a underground lab that is producing it and making what they're advertising as a accurately dosed sterile product that is branded under their underground lab brand, essentially. Okay. So for folks that want to do this in a little bit more of a responsible way and go and see a doctor, there are a lot of these dock-in-the-box operations where they're basically just T-Docs. I don't know how they're operating. I assume that a lot of this is telemedicine.

I don't know how much longer that will be in existence. I do believe that a lot of that stuff is going to be shut down. But for the time being, you want to just talk maybe a little bit. I know we talked a bit about this, but anything else you want to say on the Clomid, E-Clomid, HCG, T trade-offs? I think when you are trying to restore fertility in the short term and you're averse to injections and there's a lot of factors that could lead me to say clomid might be viable, but in general, if you're looking at something long term, I would say typically clomid or enclomaphein, which is a more progressive version of the drug, all but not FDA approved. Neither of those, I think, are viable long term, at least from a risk perspective. You are essentially putting yourself in a position of long term estrogen receptor antagonism

in certain tissues, meaning you're going to be missing out on estrogen receptor activity in certain areas of your body that down the line could manifest an array of issues. Like if you look at the side effects of serums, you'll see weird stuff depending on the compound. Sometimes it's ocular issues. What do we know about the long-term use of clomid? We've got more data for clomid than we do endclomaphen, which is, as you said, just a very, very close derivative of it But they both work the same way they both block the estradiol receptor of the hypothalamus, correct

Yeah, and then the zoo clomaphoene component of Clomid has two Drugs essentially in it because they will have differing effects That component of it is more have differing effects. That component of it is more anti-gnatotropic, I believe. So it's like the endclomaphing component is far more specific to the serum activity you are seeking in the hypothalamus. The zooclomaphena is longer half-life, less efficacious, doesn't even really represent the target therapy of the drug. So in general, if you're looking at cloma, that's the only one that has approval. So you would potentially have the data. But I, off the top of my head, don't know of any studies that are going decades long

to evaluate something like that. I don't know if it exists. I would be kind of doubtful it exists, to be honest. But I would think from what I've seen, at least anecdotally, take from that what you will, is typically no one ends up with a stable mood long term. It's not a sustainable therapy long term, in my opinion for the vitality component you seek from replacement therapy to begin with.

So perhaps on paper, your testosterone looks good, but it's more of a metric that you're using to justify the drug because you are achieving the target, which is look, my testosterone is better now, but at the expense of literally tricking your brain through inhibiting very, very necessary mechanisms. So it's not like you are stimulating production through a means that is directly targeted. It is more like you are trading off the health of one part of your body to get an outcome that is potentially ROI justifying in another aspect of your body. So at the expense of estrogen receptors working everywhere in the body, you're getting more

testosterone. And is it blocking estrogen receptors everywhere or just centrally? Yeah, it is selective, hence SIRM, but it's not perfect. As we talked about last time, you were going to get, we could just Google Clomid Side Effects and you'll see an array of different things, I believe, including but not limited to skewing of lipid parameters. You were the one who taught me about, you know, it's a fact. Does Monstral?

Yeah, I like that sketchy. I wouldn't want to have that long term. Like there's stuff you'd have to track that are very unknown variables. At least we kind of know what to expect when you have natural testosterone increasing, what happens at a lipid perspective or a negative feedback perspective, or you're not dealing with some, I don't know, nebulous activity in different tissues and having to account for it. So actual brain inhibition is a sketchy to me. And from what I've seen, people end up not in a good state of mind long-term on it.

I suppose it's possible you could. What doses are you seeing people use in the wild? 50 milligrams daily, 50 milligrams three times a week? Around 50. Obviously in the bodybuilding world, I told you about the absurd PCT regimens, post-cycle therapy where guys are using 100 per day for shorter time frames, but it's super high doses. Dr. Justin Marchegiani I think we're going to see a big increase

in the use of clomid and eclomid even beyond what we're seeing now just based on the regulatory environment which is to say that there will be no use of telemedicine for the prescription of any scheduled compounds. So that means that testosterone and HCG, which we'll talk about again in a second, can only be prescribed in person, at least if you're adhering to the law. Whereas via telemedicine, you could still use clomid or potentially eclomid. So that just sort of suggests that we're going to see H.C.G. kind of plummet and clomid go up. So I think the implications of understanding this are actually pretty significant and I'd really like to see this studied better because everything about clomid

is easier to use. You're going to have this, you're going to get over the regulatory issue. It's oral, it's a pill, you don't have to inject it. H.C.G. as we've talked about is a bit more difficult to use because it needs to be refrigerated. It's a pill. You don't have to inject it. HCG, as we've talked about, is a bit more difficult to use because it needs to be refrigerated. It's a very fragile peptide, and it's probably more expensive than both testosterone and clomid put together, right? Oh, yeah, for sure. Anything you want to just say about HCG that we didn't cover last time? I think that if you were looking to restore natural production or assess your testicular response in general before you

decide to go down the TRT pathway could be a worthwhile thing to do. So if you're considering TRT, you have a total testosterone of 300 or in your symptomatic 381. Yeah. And let's just say you're symptomatic. Don't even remember the last time you had morning wood. Your energy levels are much lower. It's much more difficult to retain muscle, etc. etc. Actually looking at your blood work to assess what is the release from my pituitary down to my gonads to actually

produce the testosterone, what is that signal and is it sufficient? So do I have in range, high normal, like what does it look like on my blood work of my luteinizing hormone LH and FSH? And if it looks to be adequate or even high, would be even more indicating of something's wrong, you could determine from there, why are my test is not responding to it?

I mean, Clomid gives you two pieces of information, right? It tells you that pituitary response and the gonadal response. HCG will only give you the gonadal response You're not getting any pituitary information out of it other than the shutdown, but that's not real. It's obvious Correct, but I was just saying as far as interpreting the blood work to understand what luteinizing hormone even does in general You would be looking to your response at the testes to the signal from your brain. And if you were going to use an HCG, you can mimic that, which is HCG essentially, it's not identical, but it looks very similar to LH, and it behaves in a very similar way on the luteinizing hormone coryonic gonadotropin receptor, which initiates the light-acceler

stimulation and intratesticular testosterone production that you would want to actually produce natural testosterone. And when you use an HCG, it's the only way you can directly do that if you had an inadequate signal. But the only viable way that would be something you could stick to and have as a Monotherapy as in it's the only thing you're using for your HRT is If your testes are healthy enough to respond to it to make the testosterone So when people are trying to determine if they should take literal synthetic testosterone, I feel it's worth fleshing out What is my actual health of my testes first? But let's say you learn this, okay? So let's say with my testosterone of 381, I take HCG

and my testosterone goes to 1200, 1200. Like it goes to upper end of the range. So we've learned that, hey, my hypogonadism is central. It's not peripheral. Somehow my pituitary isn't making enough signal because clearly my testes can make enough testosterone. Armed with that information, what is the best course of action? Is it to stay the course and just say, well, hey, keep taking HCG because at least your testes are responding to it or is there some obvious

problem solving. And I'm thinking about this even in my case, right? Because when I think of all the things that would normally impair pituitary function, the first thing that comes to my mind is sleep disruption, knock on wood. That's one thing I've pretty much got down in the toolkit. My sleep is great. Maybe stress, probably hypercordysalemia, maybe not so great. Training, overtraining, under training, like what are the things you would look at to brainstorm if that's scenario or the case? I don't know if that's the case, by the way, but that's an experiment that's probably worth doing to see, hey, why is my T low? Is it low because my brain isn't saying the right thing or is it low because my body can't do it?

Yeah. I think there is multiple factors here that could be fleshed out before you ended up on an HCG to even figure out what's my response at the testes level. Figuring out if you can top out the natural signal I feel is the first thing to do, pending your blood work looks like gonadotropins are low to mid-range. Why am I only getting a 381 response out of that?

It would be to look to many of the things you just said, which obviously you're pretty dialed on. And then above and beyond that, it would be assessing the basics, like micronutrient intake, macros, are you eating enough to recover relative to your training stimulus? I'm not gonna say a lot of people over-train too much.

Maybe they're just under-recovering and their sleep is bad. That's probably a more realistic outcome. But in general, there is not in your case, but in many other individuals, micronutrient deficiencies across the board. Zinc intakes not being adequate amounts. Magnesium intakes super low and that's impactful as well. An array of things, vitamin D being low, also very impactful. And these things can all move the needle like 100 plus nanograms per deciliter, potentially, depending how deficient you are. So some of these low hanging fruits with the sleep, micronutrients, minerals, actual macro intake, some people are eating ultra garbage processed foods, no micronutrient

density, they're under eating, maybe they're on semi-glutide and they're super calorie deprived and they have very low protein or something. That's also impactful. All of these assessments, do I have an adequate energy intake and of that energy intake, high quality nutrient value in that energy relative to my demands and my training hard enough to actually maximize the testosterone too? Because that's also a factor as your resistance training regimen and the sleep, all of these things in concordance will ultimately dictate what is your output. And then let's just say you've had that all dialed in.

At that point, if it's still either suboptimal signaling, so low normal, whatever it is, or even normal, can add a trope in output, and then you're still getting an inadequate response, you could then potentially discern partly that you're not gonna be able to get the signal you need at your pituitary to optimize, or you actually have some degradation of response at the receptor level in the testes themselves, which is an age deteriorated thing as well, unfortunately.

Like I would love to just say everyone's testes are gonna retain perfect function forever, but it's not the case. So similar to the signal, there's also the health of the actual organ. So if those things are all optimized, you've kind of done your due diligence. It's just making sure you actually know

what the due diligence is. And if those things are optimized, and you're at 381 and you take HCG and your T goes up, what does that imply? That there's some other factor that we're unaware of that's impairing central stimulus. Yeah, I would be like, what's your GNRH output then? Not that I know how you could even measure that, but presumably that may be low or the receptor response to the GNRH is suboptimal too. Yeah, interesting. So it's like a whole upstream. Yeah, that's interesting.

That's the problem with these. Is there anything that... You could use a GNRH agonist and even test out what your pituitary output is from there. But that's like good luck finding a doctor who understands the nuance of not castrating you with that. Yeah, although what you could do is then you could use Clomid. Sure.

Right. So then you could say, okay, if the response to HCG is favorable, then you know directly stimulating the late egg cell produces testosterone. Assuming you had enough testosterone to aromatize the estradiol that was a meaningful impact from inhibiting its negative feedback to begin with. At least with a GnRH agonist, I know I'm maximally stimulating pituitary output to whatever capacity it is. With Clomid, I'm just inhibiting negative feedback

to whatever suboptimal capacity my ER is agonized. Yep. Although you'd want to think if you gave a high enough dose, yeah, you're right. In my case, maybe that wouldn't work because my estradiol is so low to begin with. You're not inhibiting that much. That's a very interesting point.

If estradiol is really low, Clomid could fail just on the basis of that. Like if you really wanted to test pituitary output potential, you would use a GnRH agonist and see what happens. Is there one out there? Gnadirellan is often used and I think misrepresented as a HRT therapy. It is a GnRH agonist. There's other ones that are used for other indications, but like, yeah, they exist. It's interesting in that the question is what's the so what, right? Like, so this is a super interesting line of inquiry.

And let's say you learned, oh, you respond favorably to HCG, you do not respond to the GNRH. Oh, well then the problem is something is wrong with the pituitary, the pituitary is missing the signal. I've seen people diagnose adenomas by actually digging into that stuff. So I think it's worthwhile to understand because maybe you have, again, it depends how long you've been monitoring your hormones.

Like, have you always been a healthy person? Well, this is where maybe the endocrinologist can really do the heavy lifting here, right? Like, if you go and see a physician who day and night is thinking through all of the intricate pathways here, yeah, maybe there is a microadenoma. I mean, one of the things we like to do in people when we can't solve this problem before we send them to an endocrinologist is measure prolactin, ACTH, a few of the other pituitary hormones to kind of get a sense if anything else is out of whack. Yeah. Sometimes you'll have like a prolactin secreting at a nomenon and it's problematic as

well. There's a lot of weird stuff that I would love to say. You should understand this before you take hormones for the rest of your life, but it's hard to expect everyone to understand this axis to the degree where even we're going back and forth, like, what about this? You just have to find as good of a medical provider as possible, I suppose. Yeah. I mean, I do hope that people take from this discussion the following, right? Which is HRT is serious business. I do think a lot of people are doing it incorrectly. And I think there are a lot of really irresponsible people out there who are frankly just practicing dangerous medicine, if not veterinary medicine outright. And again, I don't see a lot of this in my practice. They're usually people

aren't coming to see me who have been terribly decimated by someone doing awful HRT in them. But I can see people on YouTube where I'm shaking my head going, oh my God, what's that guy talking about? What's that guy doing? So there is clearly a use case to understand this stuff before you go down the rabbit hole and hopefully this type of content helps. Anything else you wanna say on TRT before we kinda pivot to something else? Yeah, I guess just to put a bow tie

on the whole natural stimulation thing, I do think if you are mindful of fertility, it's worth consideration of HCG concurrently with whatever you're going to be using. If you're on TRT and you're going to shut yourself down, don't make the mistake that thousands of bodybuilders have where they got on hormones, ended up with atrophy testicles. And then when they were 10 years later wanting to have a child, realized the arduous recovery process was like pretty

significant. Are there guys that can recover after 10 years of TRT? So I dug into that because you asked me about a five year last time I was here. Okay, sure, five year. The longest I could find was four and it seemed to be pretty reliably restored, but there are some that just doesn't seem like. So you're saying someone is on uninterrupted testosterone replacement therapy for four years? These were abusers.

Okay. So they're on very high doses. But it's not like a controlled trial to where it's like, you're going to take super physiologic trend. It was like you guys abuse some amounts of synthetic drugs and have been shut down. And to rescue these guys, they were using recombinant FSH and HCG and megadoses? No, they were just doing whatever PCT they deemed worthwhile in general. Some of them, no PCT.

Wasn't it a trial where they all got? Oh, I see, it wasn't a standardized recovery. Yeah. But what I've seen at least from these studies, which admittedly, it's not like I'm behind them or anything, so it doesn't really matter, but they're not the most high quality controlled things, but it's very difficult to control for illegally used drugs at abusive dosages in random body building population.

So what we see though, in general, is once the hormones have left your system and there's no more residual negative feedback, there is a recovery period that could be as short as weeks to months, but in general, most people will recover within one to two years, even if abusing. Yeah. But it's not 100%. Okay. When we last spoke, we talked about a whole bunch of peptides. Just recently, meaning after we spoke, but before this discussion.

Yeah, the wild timing. Yeah. The FDA came out and took a list of about 30 peptides and put them on a list called category two. Now, this included six of the peptides we discussed, including BPC-157 and what is it? CJC. CJC- 1295. Yeah. IPAMRELAN. That's right.

So a bunch of the things we talked about are now on this Category 2 list. And I've been doing my best to understand what that means. My interpretation of what it means to be Category 2 is these can't be sold, compounding pharmacies cannot make them, and any interstate commerce of these things is a felony. That said, I've noticed that there are still sites selling these peptides, and they seem to be suggesting that they're selling them for research purposes, which is clearly bullshit.

What's your understanding of this FDA ruling? I think that the ruling has basically put them on a super high-risk list, essentially, whereby they're not outright banned, but you will invite heavy scrutiny and perhaps legal action should you decide to make them. Maybe it's not comparable, but in the dietary supplement world, they have an advisory list and they will pick certain things they think are high risk and add them to this list. And then if you continue to make or sell these, you may receive a warning letter at which point you have to either discontinue immediately or they will take you to court and you have to prove why it's to share a compliant and legal to sell. And you could have a court appearance where you could try and make your case, but

you will lose essentially. So I don't know if this is going to be the exact same outcome because it's pharma stuff too, so it's probably heavier scrutiny. But from the people I've talked to in the compounding world, people who even are in the business of selling peptides, they seem to think the common ality that I'm seeing is it is very risky. It was already risky to be honest, but it's very risky. And you are inviting scrutiny, but it's not necessarily actually illegal. They

could easily prove it probably if they wanted to and took you to court. But I don't know that all of them are going to get whack-a-mold. I feel like it might be a scenario like that. When you look at these research chemical sites, they're no different than they were months ago. These are the same sites that have been operating with their pseudo research chemical use only fake umbrella the whole time. Those companies exist to try and sell whatever with no prescription, no compounding pharmaceutical standards, like at least in compounding, there is some level of oversight where you have to be plus minus

some amount of potency. You should be submitting it for microbial testing and stuff. And in this world, it's buy it from Alibaba private label it, and then you sell it online. That's what these research chemical sites are. So maybe some of them are doing HPLC testing, but that's like the really responsible ones, if you wanna call it that, relative to the rest of them that are just straight up buying it, repackaging it and selling it. Do people buy there with a credit card

or they're not having to use crypto to buy through these sites, are they? I think it depends on how big the company is, because sometimes you could get away with credit card processing up to a certain amount until, you know, Stripe or whatever your processor determines you're doing something high risk. That's not a part of their compliant activities.

And up until that point, oftentimes they're accepting credit cards. So the bigger companies will do Bitcoin only or other more loophole ways of paying, MoneyGram, Western Union, stuff like that, typically crypto. Yeah, some companies do credit card too. So the rationale for putting these 30 peptides on this Category 2 list provided by the FDI is it's a safety question. So the question was, we don't have sufficient data on the safety of these things, so we're going to sort of schedule them in a way.

Was there anything else to it? I mean, is there any reason to believe that these things were harmful? I guess I just don't really understand what the rationale was. And by the way, I'm not saying I necessarily disagree with it. I just, I'm trying to understand what's being communicated in this ruling with respect to these peptides. I think publicly what they're saying is it's a safety concern and there's no actual FDA approval to justify the production of these and prescription of them, which is not the most unreasonable

conclusion, I suppose, given that a lot of these are research chemicals at the end of the day. Like it's not like Milano Tan 2 has an application right now for somebody who's too white. So some of this stuff is very fudged at the end of the day anyways with compounds that got abandoned in the middle of a pipeline, but people had a demand for it. So the research chemical companies have never stopped selling it and then compounding pharmacies, the ones that are willing to risk it for the biscuit, will make a certain amount in quantities that they deem is enough to satisfy the perceived demand, but not enough to get whack-a-mole potentially. So it's really weird because you would think it'd be black and white.

You don't make it or you make it illegally and that's kind of it. I think a lot of people do believe that it's gray area enough that it is still legal to make. And there are small compounding pharmacies that are going to do business as usual. I think some of them are looking to other abandoned pipeline products now to replace the existing ones because those aren't on the list, even though they're similar mechanism of action or whatnot. And you could find a catalog of Frankenstein compounds that a pharma company didn't want and get it from China and then do the whole process over again because there's endless amounts of those. Why do you think there's such an epidemic of interest in this stuff? I'm constantly

amazed at the frequency with which people forward me links to these bizarre molecules that they've heard some influencer talking about on social media and they're asking me should they be on it. My patience for it is so low, it's so thin, when it's like if you would spend, I don't know, take half the amount of time, use scroll social media, looking for obscure molecules that idiotic influencers think you should be taking, and maybe put it into working out. Call me then. Is this just a symptom of our quick fix obsession?

I think some of it for sure is, and one thing I do want to preface too is, I probably should have also mentioned, some of those compounds I do think are useful. Yeah, well we talked about them. Yeah, some of them have utility and I think are a shame that they're banned or harder to prescribe now or get or what have you.

Some of them I feel like had no use being sold to begin with and then some or things I'm sad to see. Did we talk about CJC 1296 last time? Yeah we did. And what was the upshot of it? It is a good GH RH analog So it works quite well in conjunction with growth hormone releasing GH secretagog that will essentially enhance the output of growth hormone concurrently So it's not bad. It just never made it through its pipeline

I think Tessa Moreland is superior for that purpose. And Tessa Moreland is still okay. Yeah, it's superb for lipo dystrophy and presumably it's still going to be prescribed and sold. I don't know if they're going to clamp down on the compounded version. You can only somehow get a pharma version. I don't even think I've ever seen, I think it's called a Gryfta is the actual pharma version. I don't think I've ever seen it. probably way too cost prohibitive to even see the light of day, but that will continue to be prescribed. And BPC 157 was kind of a VEGF analog.

Yeah, that one is, uh, interesting because it's like pro angiogenics that they're going to be pushing the whole, it's going to cause cancer angle or it might. So we can't really get behind it, which understandable if it didn't make it through its trials. So I get it at the same time it sucks though, because it's like we've all used it or know someone who's used it who's had benefit from it with perceptively like no downside at least that we can see acutely. So that's a tough one to see go for sure. But yeah, I think a lot of it is hype, sexy, new thing.

Oh, this mechanism that's never been targeted, like it inhibits myostein or does this or does that. You know, there's an array of different compounds that do different things that don't have FDA approval. So you want to be the first to be in a performance enhancing advantage position relative to other people too, even if you're not a professional athlete, everyone wants the competitive edge or better focus, better muscle growth, better body composition. Understandably so. But it's not clear that these things really do that much in terms of performance enhancement.

When you consider testosterone, for example, which has enormous performance enhancement, do any of these other peptides even come close? I would say in terms of like hard lean body mass and strength outcomes, no, definitely not. That's part of the thing that sort of fascinates me is all of these things are so marginal in their benefits. What would be interesting if there were infinite resources

would be to do clinical trials for specific use cases. I would actually be very interested in seeing a clinical trial of BPC for specific type of injury recovery, where there's a really clear use case. We're going to do an eight to 12 week trial in postoperative orthopedic patients where, boy, if there's one time when you want to see more VEGF, that's probably it. And let's compare that to a placebo and actually see, are we getting quicker recovery? And if so, maybe that becomes a use case for it.

I mean, maybe in part that's the challenge here. And I don't know what the right balance is for something like the FDA to strike, but they've clearly had enough of kind of the Wild West. Yeah, I do wonder what really brought it to their attention if there was some like. Must have been our podcast. Yeah. There's something presumably that brought

to their attention, this is being, I don't know, mass marketed, misused. These aren't even approved compounds, what's going on? And let's go down the laundry list of which ones have FDA approval. Okay, that's pretty easy to exclude those and the rest of them are gone kind of thing. So I believe there's definitely been an uptick in just haphazard promotion of them because it sucks because some of these do, even though

they don't have impactful outcomes on muscle growth necessarily and like ergogenic outcomes that are sport performance enhancing blatantly from a rehabilitation standpoint or potentially even a longevity standpoint. Not saying any of them do definitively, but like some of them have promise and had like really interesting outcomes and rodents that would have been nice to see what happened in a human's play out. Now granted, if they got halted in trials, probably wouldn't have ever happened anyway. So it's just random people taking it. You mentioned myostatin a second ago, which of course reminds me of something that's been going around social media lately, which is this interesting discussion about a gene therapy for follistatin. So for folks listening to us who haven't been following this,

I guess there is a gene therapy out there where you introduce a vector to somebody and I don't think you fully silence, but you clearly attenuate. Actually, no, I'm sorry, you activate the gene for fallostatin. That makes more of the fallostatin protein which inhibits the expression of the myostatin gene or maybe inhibits the protein myostatin one or the other. And this of course is theoretically interesting because of what we know about the actions of myostatin. When I think back to images that stand out from my first year of medical school, clearly on the top 10 list.

You haven't even said it, I already know what you're talking about. Yeah, you know what I'm talking about, right? Because this is still like more than 25 years ago, I still remember sitting in class when they showed the Myostatin knockout mice and cattle. And do you want to just tell people what a Myostatin knockout looks like? It produces a double muscle phenotype is what they call it. And if you look at these cattle, it's like,

you would think it's Photoshop by how absurd it looks. This is like the Mr. Olympia of cattle, essentially. Like it would be no chance anyone would come close in cattle sport, whatever. And in the mice, same deal. They have literally, they call it double muscle, essentially, because it's, you literally have double the muscle fibers as the wild type. Yeah. The reference.

And I remember like the chickens, the mice, the cattle. I mean, it was truly remarkable. There's this dog too, super jack dog. I forget what type it is, but she has the same moustache. So my roommate and I spent the rest of medical school just talking about, we've got to figure out a way to inhibit our myostatin. Yeah, yeah. Okay.

So apparently now someone's working on this and they're claiming that for just, I don't know, $25,000 for your first shot and maybe $25,000 for every subsequent shot, you can get a gene therapy that will activate and produce more of a protein called phallostatin that inhibits myostatin. And so that should be good, right? Yeah. Yeah. It seems like at least in the literature in animals, you see the myostatin knockouts and you see this double muscle phenotype, you would assume there is actual rodent data too, where you see fallostatin administration does enhance muscle, like it does happen. And I guess, as a result of that, a lot of these research chemical companies

were very quick to come out with freeze-dried, life-alized, fall-as-satten product that had one milligram per vial and you would buy it for hundreds of dollars and then you would basically shoot a vial a day or something of that nature and spend thousands over the course of a cycle, which was based on no data at all. How did this peptide get created? Is this an FDA approved drug or is this one of those? No, it was like, we know what the chemical structure is.

Let's go get an Alibaba chemist. And technically, yeah, okay, so got it. So you've got this kind of gray market, phallostat and product out there. Yeah. And this one is not gene therapy to be clear too. It literally. Yeah. Yeah. No, you're actually injecting the protein Yeah, yeah, so you'd literally get bacterial static water shoot it in switch it around till it's mixed and injected in yourself and The half-life is like a couple hours So you'd have to inject them multiple times a day to have it be stable in your blood to actually get the effect them multiple times a day to have it be stable in your blood and to actually get the effect, presumably.

And essentially the outcome that we saw in the bodybuilding world, because this has been around for a decade plus at this point, if not decades, was not really anything. There'd be the random outlier who's like, I gained 20 pounds in two days. And it's like, okay, bro, and everyone else got nothing, essentially. I think you couldn't help but think that guy was probably selling it or something. So anyway, not that impressive. And we just assumed it didn't work. And then we come to find out that there's these viral

vector studies going on behind the scenes and rodents. And there was one in humans, I believe too. And more recently, there's this bacterial vector version of it, which is being created. A lot of big names are getting it and stuff that Brian Johnson biohacker dude got it. And I've yet to see any actual metrics of before and after muscle growth or anything of that nature. He's kind of just produced apparently his follistatin increased. So presumably it's actually doing something.

It's just that outcome of more follostatin actually binding enough myostatin to have an effect that is worthwhile. Dr. Justin Marchegiani By the way, how is phallostatin measured? Is there a certified assay for measuring phallostatin? Dr. Justin Marchegiani I don't think so. I think they're using their own like internal measurement as far as I know. So they have like their own assay that they've developed. So I don't really know.

Dr. Justin Marchegiani There might not be a validated assay for measuring this hormone, but this protein rather. Yeah, I couldn't say for certain that that's actually measuring it correctly. So assuming that it is, it is increasing it. And then is that actually doing anything? The picture that you got sent, obviously looked pretty impressive. Objectively to me, it kind of looks like it has some of the hallmarks of fitness industry angles and like lighting manipulations and stuff. Just to back up for a moment, this discussion came out of a patient sent to me something off Twitter, which was like kind of a before after of someone who had done this gene therapy.

But just for folks who aren't in the space, including me, although I feel like I kind of can see the bullshit when I look at it. But walk through the how do you take a pre and post photo and create the most difference? Because you've actually sent me pictures before of pre and post on the exact same day and they look totally different. So clearly there's no biologic difference but there's a huge aesthetic difference. So what are the tricks that people use to manipulate photos shy of just straight up Photoshop? Anybody watching has probably had a cheat day. When I say cheat day, I mean just the day you go off the rails and eat whatever junk you want where you had horrendous distention of your stomach to the point where it almost looked like you're holding an alien baby or something like that is not uncommon for us to have all dealt with at some point some really bad digestive problems and

a lot of times these before and afters are not actually shot I'm not saying this is the case with this before and after by the way I'm just saying in the fitness industry pretty typical especially Years ago when they could get away with more egregious examples of this and it's gotten a little bit better now But now there's Photoshop and all that shit. But anyway, You could and what is typical people would take the after shot and they would get their pump They would make sure that they have heavy down lighting They'd be like oiled up potentially in the perfect circumstance essentially for even temperature vasodilation

Changes just in temperature very massively. So you want a higher temperature presumably? Yeah. So if we went in your gym and we cranked the heat and I did five sets of curls, five sets of something, I could get my arm vascularity to look unrecognizable compared to what it is now. And then I could walk outside and you would see me just like disintegrate in front of you essentially as it all vasoc constricts from the cold so that is something that is

very abused in the before and after kind of transformation shots where they will achieve a transient look that is not representative of them walking around and it is certainly not representative of the complete opposite circumstance that they representative of the complete opposite circumstance that they do the before shot in. So they will do everything perfect and take their after shot, which is as good as they can possibly look with all circumstances accounted for, which is actually shockingly as much as you say you're aware of it and you know how what goes into it and you can call obvious bullshit. You'd be shocked how many people in the fitness industry still can't do that.

They'd be like, how'd you gain 30 pounds of muscle in like three weeks? It's like, dude, you should know this. You watch these videos all the time. Come on. So anyway, and then you would take the before shot and depending how egregious you want to make it, you go on much worse lighting after you have successfully downed 4,000 to 5,000 calories of processed garbage food. So you actually are swelling, you're so inflamed.

Yeah, think of everything you could do to look as horrendous as possible, even down to the facial expression of looking disappointed on camera with how abysmal your physique is. And of course, you deliberately stick your gut out to exaggerate it. Yeah, it's not hard because you're so distended too. It's just like exaggerated plus you're distending it plus you're looking disappointed and you're not flexing Yeah, you're rolling your shoulders forward instead of rolling them back. You have no pump. You just walked outside You've been hanging out eating shitty all day There's a lot of things that it sounds like these factors are not significant enough to make this big of a difference

But it's you see them all stacked. Yeah, and if you haven't gotten to 10% body fat or less, I can't highlight enough how dramatic it can really get. Like sometimes you will see a guy who's 150 pounds who's shredded. In the perfect lighting circumstances, the guy could look like a Mr. Olympia competitor through angles, lighting, etc. And then you see him in real life with a t-shirt on, you're like, dude, do you even work out?

That's how dramatic it gets. I don't know why people don't, well, I think I know why. I think a lot of people have never got there to know what the difference is, but when you're lean, it's a pretty dramatic how much you can fudge things. And it is abused to high hell by people who want to sell things.

So anyway, in this circumstance, I'm not saying that's what happened. Like there was a pretty impressive before and after for what is supposedly, I don't know if he used drugs alongside it. That wasn't really at least clearly disclosed at the glance I took at the caption. Maybe it was, but there was no change in nutrition

and exercise supposedly. He looks quite a bit better, but the sniff test was a little bit like, you're kind of like sticking your head out a bit. Are you trying to look worse? So I don't know. He seems like a nice guy, the guy who's kind of like at the forefront of speaking about its utility and all the viability it may have in regenerative medicine. And there's no viralizing outcomes either, because it's not acting through AR. It's like an independent mechanism. So it sounds cool in theory, but the outcomes we see at least clinically have not been impressive

enough for me to be floored by it. So I'm not sure if the transformations we see online are typical or if they're a little bit exaggerated or what, but I think there's some level of potential exaggeration that comes with this stuff. Yeah. And how much muscle mass are they? Because they did a sort of open label trial, didn't they? But the phase one.

Yeah. Yeah. So they, I don't know if it's published now or if it, I think he said it will be soon. I think they're submitting it. I don't know if it's been accepted anywhere. Yeah. So it looked like the lean body mass gain was statistically significant, but not that impressive from what I recall. It was like two pounds. Yeah, something like that. And then what do they have like inflammation markers, which were kind of like stayed the

same. The only p values to my recollection that were statistically significant was an increase in lean body mass. You said to the tune of about two pounds. I think there was something else. I don't remember what it was. A slight reduction in body fat. Intrinsic biological age. I don't know if you want to speak to the validity of those tests because I think you're there is

none. Okay. Okay. So those are meaningless. I think there're... There is none. Okay, so... I think those are meaningless. I think there was about a 1% decrease in body fat that was statistically significant if my memory serves me correctly. It didn't seem like they controlled for exercise or anything, so I don't really know how... what the takeaway is. I was surprised at how little the effect was if this mechanism matters. And it might not matter. In other words, it

might be the case that while knocking out the myostatin gene at birth produces a profound muscular phenotype, attenuating the gene later in life might not do much. I did ask one of my analysts to look this up today. She found an experiment where they took mature mice, call it like a two year old mouse, and they did a near complete block of the myostatin gene. So not 100% knocked out, but like more than 99% of the mRNA was deleted. And it did increase muscle mass in the mice by about 25%. But 25% increase in muscle mass is significant, but that's at basically completely knocking out myostatin. Whereas if you do that at birth, as you said, you're going

to more than double muscle mass. So that also suggests that best case scenario, if you did this in a developed individual, you're going to get big results, but it's not game changing. And of course, doubling or tripling, fallow statin levels, which kind of indirectly work on this pathway, it's possible this would have no effect. I mean, you'd have to see this studied more rigorously, potentially with people who don't have a conflict of interest, which is also something you have to be careful of when you look at this type of literature.

But I don't know, I guess I wouldn't bet on it would be my two cents. apparently there's a phase two trial that is happening either in Canada or Japan and then there's six months results that are more impressive that they're highlighting. So and these phase two studies are specifically for sarcopenia. So I'm assuming they're recruiting people over 60. Look, if you could add five or 10 pounds of muscle to somebody over 60, that would be really impressive. Do we have any insight into how much training stimulus is required to produce these effects?

I don't know what their phase two trial is going to encompass or the inclusion criteria or anything, but I don't even know if they're using training in the phase two. Dr. Justin Marchegiani To me, an interesting study would be a placebo, a placebo group that trains, a treatment group that does not train, and a treatment group that trains. That would be a very interesting comparison. Dr. Justin Marchegiani Yeah, no for sure. Dr. Justin Marchegiani Because I'd love to see placebo who train to no stimulus treatment. You get two very elegant comparisons with those three groups.

Yeah, that would be great. And like this stuff has definitely been hyped for years. So if there is a way to actually get the answer finally, like does fallastatin work in humans and produce an outcome, that is something you could avoid anabolic entirely for the androgen sensitive that might otherwise need anti-catabolic action in later life or in a burn scenario or whatever. Like that seems like pretty useful to flesh out because SARMS definitely didn't pan out the way Pharma had hoped. Now what's interesting though is wasn't there a trend towards didn't everything move in the wrong direction? I don't know if it reached statistical significance on lipids and metabolic markers.

Yeah, I don't really get it. Resting glucose was elevated. Insulin went up, HDLC went down, Triggs went up, LDLC went up. So all of those things kind of moved in the direction you would not expect if this were beneficial. One thing that is weird is this fallow statin, when I was looking it up, I kept seeing the FSH inhibition statements and I was like, is this some sort of like precursor and I'm misinterpreting the acronym because surely it's not intertwined with.

Follicle stimulating hormone. But it turns out it actually used to be called follicle stimulating inhibitor hormone or something. And it's like primary mechanism that was known was how it would inhibit the production of FSH at the pituitary, which is really weird that that is something that apparently the isoform used in this vector is one that is less specific for that component of what fallow stand typically does endogenously. But that is, I don't know if there's some off target mechanism that is resulting in the glucose aberrations or whatnot, but like, I have no idea what

would be causing it. Well, it'll be interesting to see the phase two, as you said, and hopefully they study it with a large enough sample size that you can sort of make sense of it. Anecdotally, there's some like big names that are using it and I don't know if it's placebo or what, or if some of them are getting good results and it's just like outliers. I don't know. I don't really know. Yeah, I got to tell you, my interest in hearing about what celebrities are achieving using any sort of treatment is zero. And I'll tell you, just for people to understand this nonsense, it doesn't matter what celebrity X achieves using drug Y. If you have no idea how their diet has

changed, how their exercise just changed, how many steroids they're taking alongside of it, whether they're being paid to talk about it, like all of these things so dramatically impact what message gets filtered down to people that I just don't think we could work hard enough to increase the scientific literacy of people to help them make sense of this. Just notable, by the way, for anyone watching who's not a member of the drive, this is why I pay for your membership is like the trust factor I have in your stuff is above and beyond any piece of content I consume essentially. There's no bias, there's no financial incentive.

Even to the degree of you don't push companies you're an investor in, it is just legit facts, totally unbiased. Here is Peter's opinion with no incentive inherently manipulating my opinion whatsoever. I just want to say I really appreciate what you do and anyone who's not a member, you should go be a member right now. Thanks very much. I really appreciate that. Okay. I want to pivot a little bit to talk about something. You made a video a while ago. I thought it was a great video. I don't know how long ago you made it though.

It was all about appetite suppression tricks that bodybuilders use. And I think the purpose of the video is, hey, for those of you, most of you who are not bodybuilders watching this, who still want to shed a few LBs, these are some tricks that can be used, dietary tricks. Do you remember some of that list? Yeah. And I do want to preface when I say this, that when bodybuilders are trying to get very lean, it gets to a point where you're pulling out all the stops to an extent whereby it's not necessarily reflective of what is the optimal healthy diet. Sometimes it's to the extent whereby it's not necessarily reflective of what is the optimal healthy diet. Sometimes it's to the extent of short of any attempt at micronutrient density,

how do I hit my protein and satiate myself to the maximum extent and fuel my training with enough carbs and have enough fat that I don't have hormone suppression. Those are the metrics. Once you get to the end of a dieting phase. Now, that's not necessarily indicative of what everyone's going to do because most people just want to see a hint of abs for the first time. So you don't need to take this to the extreme. I interpreted your video as this is the full suite of things you have. Sure. You wouldn't do all of them simultaneously. You

kind of pick and choose from this list with what works. Correct. I guess I just definitely want to make sure because people watching your stuff know what high quality food is and I do not necessarily advocate for these in all circumstances. But diet soda, quite useful for calorie restriction in my opinion for maintaining some satisfied sweet tooth. I think Lane has published a really good video recently highlighting that even compared to water, I'm not suggesting replace it with water, but in a state of calorie deficiency, if you have a craving, you're probably better off drinking a diet soda than you are eating some calorie rich, fat, laden, sugar bomb dessert.

Even some of the keto treats that you see that are marketed as healthy and diet conducive, oftentimes look at the nutrition facts. You'll note the calorie component is horrendous. So just because the sugar content might be low, the fat content proportionally to make it taste good is far more destructive to your actual body composition goals. So that is something of note as well. Some of the first things I do typically that are low hanging fruit are trying to maintain the same volume of food on my plate, but just replaced with more calorie light options.

So as much as I love the micronutrient density of red meat and it is one of my go-tos, I will consider swapping some of it to chicken breast, for example. Not necessarily saying to do that long term, but it is certainly an easy way to maintain if I'm having a six ounce portion of meat in a meal to hit my protein needs, having a lean chicken breast as opposed to my ground beef that I had at the grocery store, the difference in calorie to protein content is pretty significant.

One of the first low-hanging fruit things I do is see how can I replace what to me perceivably is the same amount of food, but just with lighter options. So that will be going from a fat-filled Greek yogurt to maybe a more fat-free Greek yogurt. And it doesn't taste exactly the same as you remember it, it's pretty damn close and the calories are perhaps a fraction as much and you're still getting proportionally the protein you need. Swapping some red meats to whites, eggs going from some eggs with egg yolks. If you sprinkle in some egg whites with it as opposed to just all whole eggs, you can still get yolks in and get your micronutrients, but it almost tastes indiscernible different when you have just maybe like one or two of them replaced

with egg whites as opposed to the whole egg. There are little things that are just noticeable, but not enough for you to consider it. Oh my God, I'm in a deep deficit right now and it's like, I'm starving. You almost don't notice that That in itself, just even three things I mentioned, you probably could have chopped off 500, 600 calories. An egg is 80 calories per large egg, I believe. Could be even higher depending on how large it is. And then an egg white for the proportional amount of protein, I think is like 30 off the top of my head.

Could be wrong on that, but something like that. Chicken breast, I think it's like 30 calories per cooked ounce, depending on, you know. This is why I like Wild Game, because you're still getting red meat, but it's super lean. Yeah, this is one thing I was gonna ask you on our podcast for my channel too, is like you pound these venison sticks that are so lean and great.

How would you, as a budget friendly person go about getting your protein with the most lean cuts? It's pretty cost prohibitive to get the really good bison, venison, stuff like that. One option is if you want red meat and you want to build it, I think you just go hunting, right? If you shoot one large deer, one elk, that's going to feed your family for more than a year. See, this is unconventional advice, but that is like actually practically applicable advice for what is budget friendly. Yeah. And by the way, people would say, oh my God, like how do you shoot an elk?

I mean, you know, it's impossible to get elk tags to shoot big elk. Well, guess what? It can be a cow elk, like a cow elk, a female elk. Those tags are over the counter. Anybody can get them. You're not trophy hunting. States regulate how much you can hunt. You get incredible meat from the cow. I would argue that's the healthiest thing you could eat, frankly, is wild game because these animals are completely unstressed. So I think those are options if you're sort of doing it on a budget because the amount of meat you would get out of a cow would more than feed you and your family for a year.

What would you think? I don't even know if this is the right question to ask because I've never hunted. So I don't know what this looks like as far as the costs to get what you need to hunt with whatever licensing you need, how many states this is viable in and then also skill level. Does it take a long time to even get to a point where you could successfully achieve? The big divide is if you wanted to bow hunt

versus rifle hunt, it's much, much quicker to get there with a rifle than a bow. But also, I truly believe rifle hunting is more humane. A person who's a really good shot, believe me, it doesn't take that long to become a really good shot with a rifle, you would be able to shoot an animal within,

inside 300 yards or 400 yards and the animal would die immediately. So there's no suffering involved. That would not be a terribly expensive proposition. Now, maybe the first year it is, but remember you amortize the cost of your learning and buying a gun and things like that out over the cost. I mean, I'd have to sit down and do the calculation, but I think that would be less expensive than if you were spending that much money on meat for sure, because you're going to get thousands

of dollars worth of meat from that. Definitely sounds better than what I used to do, which was buy really shitty frozen chicken and boxes at Superstore. I'm sure I said this before on podcasts, but the more I've eaten and migrated my diet more and more towards wild game, the less I can really tolerate. I mean, I can't eat anything that's farmed. Even chicken, chicken is just so nauseating to me in general. But anyway, it's just everyone's palate is somewhat different.

Yeah, that's one of the problems with getting exposed to better food too, is you develop this refined palate where the stuff you used to get away with that was super budget friendly and you lived on, you thought was fine, now tastes horrendous. But anyway, aside, some of the things like I think the meat discussion is definitely useful. I hadn't even thought of that. So that's worthwhile to note. What's your advice to somebody who's trying to lose weight, but in a sustainable way? In some ways, when bodybuilders are doing it, it's not really sustainable because they're really starving themselves down to a competition.

And the way that they're eating during that period of time, it's so catabolic that they're destroying their endocrine system along the way, but it's short-lived and they're gonna refeed when they're done. And so while we can talk about all of the different things that they might stack and do all simultaneously, what's your view on the sustainable way to lose 10 pounds and keep it off in terms of deficit?

I think your perception of what bodybuilders do as far as aggression towards their diet is hinged on their final outcome and how steep it is to get there cumulatively. But the way they arrive there, no one is more mindful of preserving tissue than bodybuilders. So in other words, they're not creating huge deficits at any one point? Eventually they are. At the point that they absolutely need to, but they're more careful than any human I know. Oh yeah, I would believe that. So if you were to try and take away from a bodybuilder,

how would I apply this when they're stepping on stage at literally dice to the socks, 5% body fat, it's not that you're getting there, it's that you're stopping at the eight week out from competition mark of a bodybuilder, maybe not eight, maybe like 10 or 12, but the process they took to get even there was very staggered, calculated.

And by the way, 10 to 12 weeks out, what's their body fat relative to that five they're going to step on stage? It depends at what level and how on track they are, but some of them are starting at like 12% body fat. Everyone has different goals of what they consider good. So maybe this is like my skewed fitness perception saying 10 week old bodybuilders, what you should shoot for. But just in general, the process they take to get from their peak body fat percentage to stage lean, no one is more mindful of tight trading accordingly,

the macronutrient and micronutrient input to sustain training volume two, because they need to actually make sure their training doesn't deteriorate, because if it does, they're going to lose tissue. So taking from that, you see them at least hitting one gram per pound body weight in protein without fail. And they will hold that until the stage? Unless there is some like, maybe on the week of they're already at their target body fat. And then at that point, they're trying to do tactics to make their stomach as not full of anything as possible.

So what they do on the last week doesn't really count. Okay, okay. Up until a week out. But up until the week out, they would still be taking one gram of protein per pound of body weight. Typically. And to your point, at this point, you can't be doing that with steaks because there's way too caloric. So you are on the chicken breast protein powders. Depending on the person, though. And I guess it depends on, again, the quality of your meat, because it's way too caloric. So you are on the chicken breast protein powders.

Depending on the person though. And I guess it depends on again, the quality of your meat because it's like, I've seen the macros on your venison and it's basically just protein. Yeah. Yeah. So basically the staggered approach you want to take is that you don't really want to lose more than, I think typically it's like 1% of your body weight per week

is a general rule of thumb, which is I guess could be depending how obese you are, could be a little bit aggressive. But even let's just say a pound a week maybe is like maybe a more reasonable target. But in general, if you are and this is kind of a perhaps a more applicable cookie cutter recommendation, one gram per pound of body weight, which I think everyone would essentially agree with in a deficit to sustain tissue, lean tissue, muscle mass. Then from there, you want to be whatever your maintenance calories is, which is, it might take a little bit of finagling to figure out what this is when you've never done it before. But there are calculators online that roughly ballpark give you what will be plus minus 300 calories or something of what it takes to

Stably hold your body weight for if you ate that diet it wouldn't go up or down What I do typically is I take that number and I say use your exact diet for a Week with this calorie amount like this is your diet model and this is your totally calorie goal for the day week with this calorie amount, like this is your diet model and this is your totally calorie goal for the day. Eat exactly this every day and then see what the average is at the end of the week. Cause just going by a daily fluctuations could be wildly different. You might jump up or down based on water, based on food volume, based on if you took a dump or not.

By the way, when did bodybuilders come off creatine? They don't. They'll take creatine to the stage. Yeah. They used to think you should come off because it's bloating. I'm sure Lane would tell you the same. But most of the water weight is in the muscle. Yeah. It is helpful for cosmetic appearance and for sustaining training performance. Got it.

So it's anti-catabolic. Interestingly enough, it's one of the only natural compounds that may inhibit myostatin too. So it has that upside. And it's all the things it does from a neurological standpoint, perhaps fertility, it's even used for depression now in women at like 10 plus grams or something, which is crazy. So a lot of use cases are coming up. But overall, we all know it works for muscle, for performance in the gym, as well

as volumizing the muscle. Would you say creatine is hands down the best over the counter supplement for performance? For sure. Can't think of anything off something I had that would be superior. Depending on your sport though. Yes, if weight is everything, if you're a cyclist or a runner,

the downside of the extra five pounds of lean mass is- Perhaps, yeah. Probably not very much. But making sure you have some sort of number you're going to adhere to and you know how to measure every day which basically is just reading every nutritional label you have and becoming intimately aware of what you're ingesting. If you put something in your mouth, you count it regardless of it's a sauce, regardless if it's a drink, regardless if it's a lick, you count that shit. Do most bodybuilders use like an app to do this or can they just keep tracking their head after a while?

After a while, they are so in tune with it, you can look at a piece of meat, know how much it's going to shrink after cooking, know how many ounces it is, how much that equates to in protein, calories at a high level. It becomes so ingrained that you don't even need to track it because you can literally look at it. Maybe you'll keep the calorie count and the protein count, but you know what you're looking at and you can just write it down quick.

You don't have to go look up and cross-reference, you know, on my fitness pal, what is a chicken breast, one ounce cooked, equal. So you can at least look forward to, even though it's cumbersome and arduous at the start, eventually it becomes so habitual you'll just know it. So you have a target calorie amount and you eat that every day for a week

and you see if your weight goes up or down. And if it goes up, you know, you're eating a bit too much. If it goes down, you know you're in a deficit and you decide from there is the weight loss too fast. If you lost three pounds in a week, perhaps it's too fast. And you wanna kind of like, titrate it back up a little bit. But ultimately you can kind of shoot for

once you know your maintenance, some amount of calories where you're dropping 300, I feel like is a good deficit to start at. Cause ideally, and this is kind of the whole general approach without getting way too boring for everyone, is you want to keep your protein where it needs to be, which is a gram per pound. You want to have enough carbs to fuel performance,

which depending on what sport you're doing can vary. But without getting too complicated, a good split, a lot of people follow is 40% protein, 40% carbs, 20% fat. And this is kind of like a ratio that allows you to sustain hormone production and have some amount of fat that supports it carbs for some level of gym performance and then protein for hopefully hitting your goals. And it'll depend on the person and modulate accordingly. But that's just a general framework people can start with. So that's a pretty low fat

diet. Ish. The fat and the protein would typically stay around neutral and you would typically lower the carbs accordingly, depending on how intensive your exercise regimen in sport is. But in general, I feel like that's like a minimum amount of fat that would be no lower than that is kind of what I'm saying. What are some of the concessions a person has to make to get that low in fat? I think I'm probably literally the last time I tracked my macros, I was almost exactly one third, one third, one third between the three.

And I didn't feel like I was like eating a ton of fat. Typically when you are eating meat, you will achieve the majority of that through the fat content of your meats. And it will depend how lean of the cuts you are getting, how many eggs you are eating. But I'm just thinking like the olive oil on the salad and stuff like that. Yeah, but I guess that's like. They're just cutting that out. Yeah, like olive oil on a salad is one of the first things

I would be looking at as you probably just added what 200 to 300 calories to a big salad, if not more. So unless you're Brian Johnson are willing to get like 25% of your calories from oil, probably not a bodybuilding conducive macro allotment. Even though fat is satiating, it's nine calories per gram. Where do bodybuilders get the majority of their fiber? Typically, it will be through veggies if they're having them, and those are going to be proportionally

lower calories, I suppose, but oftentimes fiber is not, I don't know, some of them use like supplements to like psyllium husk. I don't want to get into like a fiber debate necessarily because I don't even know like what the actual answer is there. But in general, bodybuilders aren't really paying. Right. They're not optimizing for health if we believe fiber is healthy. Yeah.

And I'm not saying neglect it. Like I think that it is important. I'm certainly not saying remove your fiber in order to achieve your deficit. I'm just saying that you can proportionally get to your goals almost certainly by modulating carbon take essentially exclusively, typically. Yeah, and that's gonna be in the form of starchy carbs then.

Yeah, and like you can modulate the type of foods you're eating too to accommodate the satiety is ultimately the takeaway From me because when it comes to actually describing the nutritional literature, I hate it as much as you dude It's not like something I like to talk about. Oh, how much fiber should you keep in? I don't know man a decent amount like some But enough that you can go to the washroom properly and it's some healthy amount But ultimately what I've seen in the bodybuilding space is modulating carbs up and down accordingly based on needs in the gym and protein stays at an amount that is anti-caterbolic or conducive

to muscle protein synthesis in a surplus. Fat is some amount that at least supports steroid hormone production as much as you can tolerate. And then carbs is like the most performance enhancing macro in terms of actually driving your performance outcomes in the gym, volumizing the muscle, having glycogen topped out, etc. And from there, I would typically recommend a 300 deficit and literally milk that. And that week prior to show, how many calories is a bodybuilder typically down to? If they're stage ready and they're natural and like sub 200 pounds, like they might be

down to below 2000 calories potentially. If they're a top IFBB professional, Mr. Olympia competitor who weighs 260, they could be at 2500, 2600. It kind of depends. Which is interesting for many people listening, that sounds like a lot of calories still. But you're saying given how big they are and that they're still training pretty hard,

but it's a pretty big deficit. It also depends how much they're willing to lean into cardio, because some guys will actually prefer to just diet themself into the body fat and not do any cardio because they just don't like it. I wouldn't recommend that though because one thing I have learned over the years is from a nutrient partitioning standpoint.

Actually moving when you're eating is going to produce a better body composition typically than trying to just diet the whole deficit. So what we see even in like the IFBB with these top body builders who are trying to not get fat as they eat exorbitant amounts of food and they're on insulin and HGH and huge amounts of antibiotics, they are doing things like going for walks after they eat their meal, which is more potent than metformin and controlling blood glucose.

Like they're actually making sure they are moving around and actually shuttling nutrients as much as they can even outside of the gym. Some are lazy and don't do that, but the ones that are trying to make the most use of maximizing the calories. I see. So the mobilization doesn't require that you're clearly not going to oxidize everything you ate. Like if they just ate 800 calories, they're not going to burn 800 calories on a walk of any duration, but just getting out there and walking, you're saying leads to better fuel partitioning. Seemingly. Yeah. Interesting. And I think that is, and you could correct me if I'm wrong.

I mean, I've certainly anecdotally noticed the improvement in blood sugar. Yeah. Yeah. Even for stabilization of like energy levels too, like making sure you're not hanging out on a couch with your spike blood glucose seems to be pretty impactful, not just for mental performance, but also for partitioning and actually optimizing body composition too. And that's an enhanced rank set guys eating exorbitant amounts. But anyways, backs of the blame in general, you're in a 300 deficit, you kind of milk that for all you can. And by that, I mean, the biggest problem and I guess one of the biggest takeaways from this whole discussion could be that the people who aggressively cut way too fast will end up losing

more weight off the bat, but they will end up in a state of adaption faster, whereby you are basically going to not only expend less calories at rest via the depression of non-exercise activity, thermogenesis, which is like fidgets and moving with just like your everyday activities, you will actually start to subconsciously do that less. In addition, you are pushing yourself to a state of nutrient deprivation much sooner than was necessary to achieve a fat loss outcome. So rather than trying to lose six pounds in two weeks, why don't I go with one to two pounds at most and actually milk what I can out of that little tiny calorie increment before I decide, okay, do I need to then add some more cardio to my regimen or do I want

to decrease food by another hundred calories or do I want to then add some more cardio to my regimen? Or do I wanna decrease food by another hundred calories? Or do I want to add metabolic enhancing pharmacology? You can actually make the call at that point because you've exhausted the actual increment and you know you're not unnecessarily depressing hormone production. And also putting yourself into a whole of what is essentially a malnourished state.

Because if you push too hard and you go from, let's just say you're eating 2,800 calories a day and you instantly dropped an 1,800, you will lose a ton of weight off the rip. And you'll think, oh, this is great. And then very soon you will get to a point where it's like, holy hell, I am starving. This is not sustainable. What am I doing? What do I do next? I plateaued now. And where do I go from here?

It becomes easy to dig yourself into a hole if you're not careful about this titration down, essentially. So I typically recommend trying to milk what you can until weight loss has averaged out at neutral for at minimum a few days, but typically a week. And then from there, because as a natural natural you are very susceptible to major aberrations and hormone suppression if you are going to deprive the hell out of nutrients and especially if you're doing huge amounts of cardio concurrently because you think that's what you need to be doing also don't put yourself in a hole on the energy expenditure side try and do what you can in a tight trading manner. I

sometimes wonder if my low testosterone is in response to how much fasting I used to do, because I used to always do a check of testosterone. I would do full blood work before and after a fast. So if I was doing a seven to 10 day water only fast, which I was doing once a quarter, the change in hormone levels after seven to 10 days of nothing was profound. So if my testosterone started out at five to 600, it would probably end at one to 200. Total T. If my TSH was two, it would go to four, maybe even higher, maybe even six. But free T three and reverse T three, if free T three was two and a half to three,

and reverse T three was 12. So the higher the free T three and the lower the reverse T three, the better thyroid function you have post fast, that free T three would go maybe from three down to one and a half. And the reverse T3 would go from 12 to 32. Yeah, not surprising. Yeah.

And so I just wonder if repeating that cycle over and over and over again has maybe impacted endogenous production. Although interesting, my thyroid function looks stone cold normal. It's just that my T is very low. Yeah. I would be interested to see like what your gonadotropins did when you went back to normal dieting at that point. And then how you responded from there.

Cause if you could see like a trend in your testicular response to and how your brain was shooting things out, that'd be interesting. What about things like carnitine, caffeine? What role do these play in weight cutting? Not nearly as much as good diet choices. So I would love to get into the fat loss pharmacology momentarily. There's a lot of diet hacks that we could take all day talking about, so I don't want to bore the audience, but one thing I do want to mention that is super impactful is protein

ice cream. I don't know if you've ever had this stuff, but there's this thing called a Ninja Creamy, and it's basically a mixing device. The ninjas like the blender. Yeah, but this one in particular is very popular lately because of the consistency of ice cream that it creates. What's it called? Ninja Creamy, like C-R-E-A-M-I.

So it's not the blender, it's a device that's different from their blender? Correct. So this thing mixes what blender. It's a device that's different from their blender. Correct. So this thing mixes what is already blended into an ice cream. So you would put it in the freezer, blended, and then you'd put it into this thing, and it would turn it into an ice cream consistency. Got it.

And what do you put in it? How do you make it? Well, it depends what you want to put in it, because you could make this as healthy as you want, which is essentially just like whey isolate, plus some non calorie feels like sweetener, if you want to risk it, maybe some sugar free pudding mixture in there too, like a chocolate or something. And from there, you could have something that is like 300 calories, if even, and is as good tasting as horrible ice cream but hits, you know, like a 60 gram protein hit with super high quality stuff, minimal sugar content is like 80% as good as something you

would buy in a store almost like the consistency makes all the difference here because it's like typically and this was how it worked when I was younger and I first tried all this stuff is And this was how it worked when I was younger and I first tried all this stuff is Perhaps there was a similar device, but at the time I was using a standard I think it was a I forgot which blender it was from Costco But I tried a ninja a different one before another one. I used to put in like huge amounts of ice Fruit you could do fruit to obviously and make it but basically the consistency I got out of it was not that attractive So it was not like you could tell it was an ice cream You're kind of eating like this sludgy healthy thing

But this it's like you could make it near not identical, but pretty damn close I'm actually derailing our conversation to come back to it like that's how significant it is So for people who are wanting that sweet tooth, but if I make a protein shake, yeah, what I'm gonna use is real simple I'm gonna use almond milk or cashew milk. So as my wife calls them, nut juice. Like a whey protein. I'll typically mix the unflavored ProMix. Do you know that, Bran?

No. ProMix, I think it's, maybe I'm getting it wrong. Anyway, it's unflavored whey, high quality whey, but I like it. And I'll go 25 grams of that with 25 grams of one of the other flavored ones. But that way it just cuts. I still get 50 grams, but half the flavor because I find them so sweet. And then frozen berries. And that's it. Imagine that not drinking it, but actually eating it. And it takes 10 to 20 minutes to eat. But the consistency is that of actual ice cream. So I would blend that in the blender and then put it in this ninja creamy thing would blend that in the blender and then put it in this Ninja creamy thing

and stick that in the freezer? You would put it in the blender and blend it and it would be in this thing that you would freeze overnight and ideally you would have your wife or somebody mass blend multiple so you can just stick it in the thing. But anyway, once you have these frozen ones you stick it in the creamy

and then it mixes up a serving of ice cream for you. And from there you would have the same mac, but it's infinitely more satiating. Right. Because liquid doesn't satiate me very much. And it's not just the speed of ingestion though too. That's part of it for sure, but there's just some psychological component of eating something. And one of the things I can say too is low hanging fruit for dieting and chopping many hundreds of calories off is immediately anything you drink unless it's water. If you can switch it to some sort of solidified format, you will be infinitely more satiated, maybe not infinitely,

but like a significantly more satiated. So no juices, no nothing, like see if you can make that into a slush of sorts or something that you would want to, instead of that tequila I like to have, I'm going to make like tequila sticks. Like I want to freeze. Oh dude, but alcohol doesn't freeze. This is the problem. I can't make little tequila popsicles.

I know some people who do like protein popsicles, pre-workout popsicles. They do the ice cream. They do like protein brownies. Like so much stuff that can be done when you get creative. It's just you need to have a significant other who's down to do it. It's the only problem. Why do you need your significant other? If you like cooking and you like spending time on that stuff, then perhaps

that's fine for you. But like, at least for me and for a lot of dudes out there, it's like, I don't know. I'm missing something here. This isn't that time consuming, right? You're just blending this stuff up and you put it in the freezer. I'm more talking about some of the more creative stuff, like the brownies and stuff like that. People might just call me lazy or far too optimizing. I will not do anything kitchen related if I could.

Oh man, I love cooking. That's a blessing for you then. You can get really creative and actually enjoy the process. For me, I'm like, I really hope I can throw in a microwave and cook it and it's still high quality food. Okay. So let's talk about some of the fat loss pharmacopoeia. So I have friends that swear up and down by carnitine, L-carnitine. I think they inject it. So tell me about that. L-carnitine is present in red meat and depending on your diet, you may or may not be deficient in it. And it is something that can help incorporate free fatty acids into the mitochondria and help you produce energy.

And it also is implicated in certain indirect processes like AR content in the muscle, which is some of the more fringe literature, but it seems to in the presence of sufficient anabolic stimulation actually increased the expression of what you can get out of your testosterone input. So this is the main reason why people I know use it and presumably why a lot of people use it that you know, too, is it's often advertised as get more out of less androgen, essentially. But does this work if you are getting sufficient carnitine in your diet? Do you need super, super physiologic doses?

In general, if you're injecting 500 milligrams, for example, like you will be supras, so similar to creatine, you can make the argument that indogenously or through your diet, you maybe get enough. Maybe you're not going to saturate muscle stores, but I mean, it's not analogous to creatine, but it seems to be at least in supplemental form. And this is something you inject subcube daily? Depending on the volume, because it is depending where you get it, could be 200 milligrams a milliliter, 500 a milliliter. And you can only put so much water based subcube before you have lumps.

So even though it's more easily absorbed, it's still not something you wanna be injecting milliliters of. So are we back in the same problem of like where are people getting this stuff? Typically compounding pharmacies or online or they're making it themselves because it's just an amino acid that you could just buy anyways.

So homebrew sometimes. Homebrew, how are they sterilizing the water? I'm not a chemist. He's going to explain really how you would do it. But it's the same process by which you would make your underground steroids, presumably. I mean, in other words, this is a bad idea. Yeah, maybe. Yeah, this is an awful idea. Unless you know what you're doing. Because some of them are like, pretty intelligent, but I still wouldn't risk it even if I had the instruction manual personally. So in general, though, there is pharmaceutical, not grade, but like compounded versions that

are made in an environment that's been at least fact checked, depending on the rigor of the pharmacy in question, of course, because you've done deep dives into compounding, which I recommend people check out. I think we did an AMA where we covered the ins and outs of compounding. And even with compounding pharmacies, there have been enormous breaches of good manufacturing processes and that results in contaminations of legitimate FDA approved molecules like corticosteroids that have led to literally thousands of deaths.

So it's one thing when people are compounding things without good manufacturing process that you'll take orally because the gut is a lot more forgiving. But the moment you start talking about things that are injectable and now you are injecting something in yourself that's dirty, that could be a huge compromise. So, I hope there are ways for people to vet that stuff. How effective is caffeine both in terms of its effect on appetite and potentially its effect on fat oxidation? I want to touch on carnitine quickly. The reason people inject it is typically because

the oral format is only about 10 to 15% bioavailable. So you have to take literally 10x the dose to achieve the same yield outcome. And then in addition to that, when you ingest things like carnitine and choline, there is a potentially unfounded but still potentially concerning scenario where there is TMAO conversion. So when you ingest a lot of carnitine, like four plus grams to get your yield that is enough to actually have some sort of effect that has shown to have some hopeful AR content upregulation, which is still like a fringe thing you're seeking that may not be ultimately founded. You are using an amount that is going to have some level of conversion that you could avoid by injecting. So you are averting the need to use

as high of a dose. And in addition to that, you are potentially avoiding some level of risk from gut related circumstance. Some people use Allyson with it to kind of like circumvent and try and prevent TMAO conversion. It's from garlic and it seems to attenuate TMAO conversion in the gut. But it's also like a fringe application with like a hopeful outcome that I guess you can measure in serum your TMAO before and after Allicin versus not and see if there's a difference. Are there any clinical trials that demonstrate any efficacy of injectable or oral L-carnitine? With carnitine the results are mixed. Some of it looks promising and some of it doesn't.

So if this is one of those things where you largely go by anecdotes and with it being a natural amino acid, a lot of people that use it, it depends on their baseline circumstance too. The deficient will obviously get more. Exactly. Like you could sort of see a scenario where somebody's like a vegan and then you might see, well, maybe the risk is worth the payoff. But if you're an omnivore who happens to eat red meat, I don't know, maybe it's less so. I'm sure if you saw the data, you would not be convinced that it's worth trying. So I'll just put that out there for people who watch your stuff.

I don't think that they would blindly want to inject this. The reason people find it very attractive is because it works for a different vector. People anecdotally have seen muscle growth outcomes on the same dose of anabolic or less or so and a grow leaner when they use it. So it's not like there's literature to show when you're on testosterone plus carnitine, you get better results than just test, but that's what people claim and seems to be at least somewhat reproduced anecdotally. But that's speculative. I would not hang my head on that and be like, I recommend for sure you take this. So putting that out there,

I don't think it's a potent fat burner by any means, which is like the subsection we're kind of talking about. As far as caffeine, super reliable. One of the best things you could do, you know where the data lies for upper tolerability and safety. I think the FDA even has like a threshold amount that they say you're good to take.

It's like 400, which is pretty significant. And yeah, you can get some level of increased energy expenditure from that, but largely the benefit from the stimulant category, I would say comes from the increased energy you have even as you go deeper into a deficit as well. So as you enter into nutrient deprivation territory, it becomes a lot harder to even move subconsciously, let alone actually fuel your everyday activities. So I'm not to say you should become a caffeine addict to support your deficit. And it's not necessarily sustainable. But if you were going to use something to help attenuate an energy

deficit, or one day where you need a bump. Caffeine is certainly a reliable way to do it that increases metabolic output, but also reliably increases performance in the gym and has appetite-suppressing qualities and has safety data simultaneously. So I would pretty blindly recommend caffeine for most people short of special circumstances. You mentioned him being earlier, say more about that. So that is a Alpha 2 Adrenergic Antagonist and when it comes to some of these like Adrenergic type receptors, it gets kind of confusing.

Even though it's an antagonist of the Alpha 2 receptors, it will have stimulatory effects, but contradictory to what you'd expect from a stimulant that's not vasoconstrictive the same way you might get from a amphetamine or like essentially any other stimulant that works well. So this stuff raises adrenaline signaling very significantly. And there was thought that it could liberate free fatty acids via the adrenergic signaling that you could then take advantage of during exercise. Now, is the energy expanding component of it worth hanging your hat on? I would say no. But the adrenaline-inducing component is

substantial enough that some people really, really enjoy the use of it in their training and get a uptick and energy that is markedly different than through a adenosine receptor antagonism, which is caffeine. Which is caffeine. Yeah. So like it feels much more racy and aggressive than caffeine. How does it compare to like aphedrine? Aphedrine, I believe is a beta two receptor agonist off the top of my head. It could be wrong on that, but it is less euphoric, I would say, and more like

adrenaline spiking. So you feel more like almost borderline anxious to a degree where you have a sense of urgency. How long does it last? Jo-him buying half life. Can't recall off the top of my head, but it's relatively short list. But is it the type of thing that people take for the workout when they're in calorie deficit?

Yeah. Typically, you would take it before cardio or before training is the typical application, but interestingly enough, it's also used as an aphrodisiac and can enhance erections, which is weird. You wouldn't expect that from a stimulant. And also, like, that doesn't seem like the right mix of things to be super anxious and irritable. Sure, yeah.

But that's one of the things where it's like, is this a drug for you? Because if you happen to get an uptick in performance, in exercise performance, and then also, you get some sort of uptick in libido and or enhanced bedroom performance later in the day could be attractive. I would typically reserve it for a deficit whereby you have tried all standard

low hanging fruit options and you're kind of, okay, now I need to actually boost my energy in some way that is not like I'm at my wit's end for I can't do more cardio or reduce my intake of calories anymore without it being overwhelming or I'm just in like a very deprived energetic state or I got low sleep and I need to acutely modulate it so I don't use it I wouldn't use it as much as caffeine caffeine I would very easily recommend daily use in a diet I think this is something that's more use case specific and not as reliable.

One of the clinical scenarios I see a lot of that I think plays a significant role in the state of over nutrition. Again, I've talked about this when I look at somebody, I want to know these three things really quickly, right? Are you over nourished or under nourished or adequately nourished? Are you adequately muscled or under muscled? Are you metabolically healthy or not? And depending on where you fall in that matrix, you have to decide whether calories need to stay the same up or go down. Now one of the scenarios that is I think most clinically vexing is the person who is overnourished,

typically metabolically unhealthy, typically undermuscled. So that's a pretty common phenotype. You're a little too fat, you don't have enough muscle, and you're not metabolically healthy. And a big part of the driver is basically the hypercortisolemia that accompanies sympathetic overdrive. So an individual that is under so much stress, chronic stress, that you basically can't stop the glucocorticoids from chronically being catabolic to lean tissue and anabolic to fat tissue. And when you think about all the other endocrine scenarios, like we have ways to kind of manipulate them, this one we don't really. There are

certain things we can do. You can use ashwagandha, you can use phosphatidylserine. They certainly help with sleep in that setting. But do you know anything or do you have any insights into ways to manipulate that person's physiology in addition to pulling the big three important levers around nutrition, sleep, and obviously exercise. Yeah. And by the way, the Alpha 2 receptor antagonists, yo-hem-bine and alpha-yo-hem-bine, which is a bit better of a drug in my opinion, are definitely not the drugs you want to take if you're in the hypercurtisolimia. That's right. That's what made me think of it is when you brought them up, I'm like, well, that's actually producing a phenotype that a lot of people are in chronically.

Yeah. Some people people the use case again it's not like it's indicated or anything, but some people get a Significantly better appetite suppression effect out of those particular drugs too than something else that might be where you would look but anyway that aside as far as actual Anti-catabolic action the most potent thing I'm aware of is actually anabolic. There are certain ones that are more potent at antagonizing the glucocorticoid receptor and actually compete with glucocorticoids for binding.

And that's where they get their anti-catabolic action and a deficit. So something like an oxandrolone, not that you can get it now, which we could talk about, but that in like burn victims, it is literally indicated for antagonizing the heightened cortisol glucocorticoid response that you get from being in that state. So it is one of the most potent anti-catabolic drugs. What happened there? Oxanderloin was also scheduled just banned altogether. What's the

status of it? It's my understanding. And I may be not entirely correct, but it was FDA approved for many indications. Yeah. And then basically the FDA determined based on, and this seemed like kind of a nonsense thing, but meeting in the 80s where they determined that anabolic in particular anavar by extension that anabolic in particular anavar by extension had no efficacy anymore, essentially. And for whatever reason, they determined that that decision back then,

they have you up far back enough, you can find studies where they're like, anabolic steroids aren't performance enhancing. And it's like obviously nonsense, but at that time that was what the literature available showed. It almost seems like they're leaning on some of that in order to justify pulling it. We don't think it is useful for all of these approvals anymore.

And then there's pressure from that for all of these companies that have generic approved versions of it to subsequently pull it as well. I'm sorry. So the FDA pulls ANAVAR, which is the branded version of Auxander loan. Sorry. Yeah. So ANAVAR is made by a pharmaceutical company and the branded version of Auxandrolone. Sorry. Yeah. So Anivar is made by a pharmaceutical company and I'm referring to Auxandrolone, the chemical, not Anivar. Understood.

But they're speaking to the molecule, not the branded drug. Yeah. My apologies. Sometimes it's easy to conflate what laymen speak for these Anibaloxes too. But I'm just saying, then it doesn't really matter who makes it. Isn't this rule directed towards not just the company that makes Anivar, but even a compounding pharmacy that would make Oxandrolone. Yeah.

So they are saying that there is now no approved use for Oxandrolone in totality. So if you are a pharma company who has a generic version of it or you're a compounding pharmacy that makes it, there is no approved use for it. So you presumably can't justify the prescription of it as a doctor unless you can somehow lean on it. I guess it's not even off-label because there's no... Well, that's what I was about to say. So is the implication that if there's a patient

in a burn unit and a physician there says, we've been using Alexander alone for years and it's got great results, can they override that for exemption? I feel like you would be able to tell me, hopefully. I'm not sure, man. I would think, yes, I would just imagine there's higher risk to actually prove

that it was a necessity than it used to be. And then where do you get that filled? Some pharmacy that is a bit of a cowboy pharmacy that's making it, I'm not really sure. So, what I do know is compounding pharmacies are making it as of now, still. And the pharma companies that had generic versions of it have pulled voluntarily their own approvals, essentially. So these companies that had like Oxandron, which was what I know to be what used to be Anivar, which was sold I know to be what used to be anivar, which was sold multiple times.

And oxandrolone is taken, SL, it's taken under the tongue, right? If you get a trochey from a compounding pharmacy, you could get a sublingual format of it, but it's typically a pressed tablet that you just pop, and you would take it twice a day. Orally? Yeah.

Isn't that kind of hepatotoxic? A little bit, but it's one of the least hepatotoxic 17 alpha-alkylated anabolics there is. So if you look at the pharmacology of it, it is metabolized by the kidneys proportionally more than any oral agent. And that creates superior hepatotoxic outcome where it's not nothing, but it's lesser than oxymethylone anodrol or like, you know, windstrawl or some of these other ones. Or stenazol. Yeah, stenazol is injected, right? That's typically taken orally, but it's also injected in water base, but almost no one does that. Bodybuilders do, but it leads to infections very often, so they often don't

do it now. To me, listening to this, all roads point back to nothing seems to matter more than what you eat when it comes to body composition, what you eat and how you exercise. Oh, for sure. Like all this other stuff is like a rounding. I mean, it's 90% exercise diet and testosterone. And it's 10% all of the other stuff. Yeah.

And I think a good note to make, because at the last time we spoke, we had talked about the development of pharmacology and what is leading to the change in physics as of recent. And I said in order, it was like drugs and then diet and then training. I don't even remember what the order was at the last two. It almost doesn't matter when drugs are like that important for achieving the outcome on

a Mr. Olympia stage. All but, and this is the caveat that I definitely want to make clear here if I wasn't in the first one, just in case, what you just said that 90% of it is this, you do not achieve even the outcomes from anabolic without the support of a great infrastructure of diet and training and sleep. So as much as it could be a band-aid for shitty all those things, you will achieve a fraction of the results even on anabolic if those are not in check. I've even done it myself as much as I don't want to admit, but I've talked about this publicly. When I was younger, I thought, what would it look like if

I just did like I've seen hypereponder bodybuilders do fluff workouts and get crazy results being the guy who wants to experiment with everything. Maybe I'm just working too hard. Maybe I'll try like the fluff Phil Heath workout I saw or something on YouTube. Turns out it doesn't work for me at all. I basically wasted a full cycle of exposure to these compounds to get almost nothing out of it because my training was kind of half-assed. So having that baseline, regardless of your natural or enhanced, it is the fuel to actually support the recovery that may be at an enhanced level with anabolic, but like it still doesn't exist without these things. Marshall has someone done the study of testosterone replacement therapy in a non-active individual who doesn't change any behavior and how minimal the changes are? Yeah, so

the Boston study which is like the standard graded dose response study that everyone's familiar with He had two different studies that were using 600 milligrams of testosterone. One of them was a graded dose response. 600 a week or every two weeks? A week. Holy cow. Kind of 6x physiologic dose. Essentially, yeah. The other study that I think was done in the 90s was doing 600 milligrams

of testosterone versus placebo in a non-training training and then also on the testosterone non-training training individual. Two by two, yeah. Yeah. And what they found was that the, obviously the 600 group who trained got the best outcome, but the group that didn't train and took 600 test still had better lean body mass outcomes than the training placebo group. Yeah.

Which kind of spits in the face of what I just said a little bit. Although that's 600 milligrams. 600. Yeah, so. You almost need to see that on 100. You also have to draw it out over the span of a training career. Like you're not going to sustain perpetual muscle growth. And some of that is ultimately when you take steroids for the first time, there is a temporary increase in lean body mass metrics that are essentially, and you could probably speak this better than me, unquantifiable by standard metrics

of measurement of body composition. Cause ultimately the way these work is not just through the production of muscle protein synthesis and contractile tissue. It's also like the increase intracellular water that you would not hold otherwise and the increased blood volume and increase this. These are things that although they're not contractile,

they are still making up your muscle, which is largely water. So even though they do try to account for like total body water that is not muscle based, you are still some confounding level of the drugs actually facilitate this as the desired outcome. So there's going to be some of that in the outcome regardless. But I think it's unquestionable that anabolic's even if you're not training, will produce a level of muscle that is higher than if you had no hormones.

That's definitely an outcome. To wrap up, any influencers online you're particularly excited about as far as just the amount of buffoonery that's going on. Anyone that particularly has you excited. I mean, one of the things you're known for is debunking the charlatans. You've done some legendary work in this, which we'll link to some of your best videos on this.

Is there anybody you're looking at now just sort of shaking your head at like, how is this person fooling so many people? We've talked about him briefly. Gary Brecca, he has a lot of good information. Don't get me wrong. I don't want to turn this into a shitting on him parade necessarily, but the guy very heavily emphasizes the importance of getting gene testing for a limited amount of SNPs that are ultimately

very common to find in general population and then making wild extrapolated claims from that that assert all of your Elements and problems could be attributed to this and then he has good information. That's general about lifestyle training sleep hygiene But then he'll sprinkle in these like aggressive claims about methylation If you have your homozygous for C677T methylation, if you have your homozygous for C677T, MTHFR, which I am, and a lot of people are. Almost everybody is. Yeah, then you need to be taking this exact blend of methylated B vitamins, and he speaks

very articulately, eloquently, confidently, concisely, and it very much gives the impression that this guy knows something you don't know and you should be following his advice because he ultimately is the one who transformed Dana White's physique too. And Dana White speaks very highly of him. And I don't know, man. Like some of the products she sells, it's like, it's a $140,000 red light bed. Does that improve methylation? I don't know.

I have no idea, to be honest. I would assume probably doesn't do a lot of anything, but I haven't even looked into it to see because it just never even occurred to me as something worth looking into. But it seems a bit expensive, you know, objectively. Borderline, you're in a low end exotic car territory, essentially, for a fucking bed that emits light on my face. So I'm a bit skeptical. And then he has other stuff, but in particular his gene testing. How much does it testing cost? I think it's like 600 bucks. So $600 for a gene test?

Yeah. So it's like assessing, for example, if I got a 23 in me and I had my data, I could submit it to Rhonda Patrick or somebody who has one of these like automated reports and get something as comprehensive or more so with no suggestions to buy stuff after that either just like straight up here's the interpretation based on everything we know about these SNPs. And it would tell me if I had methylation impairments. We do all of those tests as part of a standard blood panel and it's basically free. Yeah, yeah, I've note that MTH of our stuff is also in your...

Yeah, it doesn't cost anything. So, I mean, $600 seems a lot given that you can do a whole genome sequence now. Three billion base pair. We're not talking snips. Whole genome sequence for $300 today. Damn. That's crazy. I don't know, man, but then you get his, you know, interpretation of it, which is, it almost feels like he's hoping you have one of the most aggressive methylation impairment, so he could point to it and say, here's why you feel this way. Like, that feels like what I'm gathering from the content, or, oh, you clearly are a worrier because of your COMT, polymorphism here.

This is why you are so concerned about little problems that you shouldn't be ruminating over. All you need is some SAMI or whatever. I feel like even if you are right, you got a needle in the haystack because there's so much that goes into genetics that is beyond these maybe common snips that have some impact.

Like for example, if I'm the most methylation impaired, sure, I'll look at B-Tain or whatever to lower my homocysteine, like totally reasonable, but like, don't assert it's the root of my everything that's wrong with me, or I don't know, like he highlights it as it just like comes across a little bit disingenuous to me, and I really do wonder how much of it is him, perhaps deluding himself, because he speaks so confidently.

It's hard to believe he's this good of an actor, or just genuinely doesn't know, which I think is unlikely. But I mean, he goes on the biggest podcast in the world and spits complete misinformation, says that T4 is methylated in the gut to T3 and like all this. What? Yeah. So if you have a gene mutation, or if you are MTHFR is messed up,

you will not convert T4 to T3. And that's why you might have hypothyroidism. That was an assertion made recently on Joe's podcast, which is pretty fucking wild to me because Joe is actually hypothyroid and has been for a long time. So you're basically appealing to some like actual medical condition he has saying you have the answer and it's your like cheek swab thing. And it's like, I'm highly doubtful that's the case. And I'm nearly certain that methylation is not the

thing that converts T4 to T3. Dr. Derecki It absolutely most certainly is not. It's a series of enzymes called DI odonases that make those conversions. And to my knowledge, has nothing to do with your MTHFR gene. Dr. Justin Marchegiani Yeah, Chris Masterjohn had a really good video recently that kind of like summarized it all. I would recommend people check out his stuff if you want to know anything about methylation. You've had a lot before. Yeah, I've had Chris on the podcast.

Super intensive and great podcast, by the way. We'll link to Chris's discussion on that. Anybody else out there that's got you excited? I guess Brian Johnson's an interesting dude who we we talked about briefly Brian Johnson the liver king other Brian Johnson the Vegan king, I don't know. He doesn't have a nickname Brian Johnson's in the world Yeah, and shockingly as prolific as each other just in their own way So yeah, this guy is the total antithesis of that guy's diet model He's like eating sludge vegan shit on camera every day and saying it's proven by data to

be the answer to longevity. I don't know. He's done the fall of Staten thing. He's done tons of stuff. He's on telomere lengthening peptides. He's on thymus regeneration enhancing peptides. Ones that are all banned now based on the thing, or at least category two. I don't think I've ever seen something

on more stuff than him. Like his protocol is endless. And I'm like, how do you control for anything at this point? The other day he added in oral monoxide at two and a half milligrams, which is super outdated antihypertensive that causes a demon. Is he doing it for hair growth?

Yeah, but it's like, okay, you've added that in, which could affect myriads of things that are also affected by the 77 different things you're on right now. Like obviously hair growth is a pretty easy metric to count, but when you're counting health metrics on organ function and stuff, I just don't really get how he's controlling for everything.

Granted, no one else is doing it, so it's interesting, but I watch with skepticism about what is gonna come of it. If it's gonna become this monetary incentivized hype train, or if he's just gonna produce the data, some like noble billionaire dude who's just doing it for the good of longevity community or what, but he's interesting.

What's up with Mr. V. Shred? I don't know, cause I have my YouTube premium, so I don't see him. You got to get on that, dude. Did you do it last night? I didn't do it last night. I'll do it. So what does V. Shred do?

He, it's like, I don't even know what to start with. The worst things he's done. The business model is, despite having seen the commercials, I still don't actually know what to do. I have that skip button that I use. In general, I think his go-tos are, here's your body type quiz and you tell me if you're like an ecto, mezzo or endomorph. I mean, remember the types at this point.

But, and from there, I will tell you the diet that you need to like actually get lean because you've been given misinformation by everyone else this whole time. And then you end up with his program. But if you're an ectomorph, you're already lean. Yeah. So if you're an ectomorph, you can do whatever you want. Is that the takeaway? I don't know.

I've heard his programs are pretty cookie cutter and it doesn't surprise me because he's clearly a hammer you at scale. I'll just recruit as many people even to the detriment of my credibility kind of guy. So I don't think he gives a fuck what happens. But also very old school marketing, but like Harvard has discovered this secret ingredient that they've been keeping from you. And it's the secret to fat loss. I figured out what it is and it does xx and x and it's like a 15 minute commercial where he's hyping this thing up and you've invested so much time to find out what it is. You're thinking there's no way I'm going to buy this

shit. You just want to find out what he's going to're thinking there's no way I'm gonna buy this shit. You just wanna find out what he's gonna say at this point. It turns out it's like capsaicin, which is from like peppers or something and it makes you feel a bit hot. And it's like, okay, so I waited for you to drop the capsaicin on me now what? And then you're selling me a fat burner that has some negligible amount of caffeine

and capsaicin like four other things, which is like pretty typical old school marketing that is not that great. Certainly not ethical. And then he'll sell it for like $130, even though it's worth $4 to manufacture. The bottle costs more than the ingredients. Like that's how bad it is. But he's giving us a discount because we made it through the video and you know, we're clear. So instead of 140, you'll get it for 99. Yeah, but on subscription, on subscription run out it for 99. Yeah, yeah, yeah, but on subscription. On subscription.

So you don't run out of course. Yeah, of course. Yeah, he's doing us a service. One of the worst ones I've seen though was him pretending to be on the Joe Rogan podcast. I did see that little commercial. That was wild. That was unbelievable.

Yeah, I don't know if Joe's seeing it, I haven't sent it to him, but like dude, it was almost ingenious level unethical. Like to actually think, you know, without even having to say it, that's what people are thinking. Oh, this guy was on the podcast. He's probably a trusted authority on X. Whatever he's talking about, Joe must trust him because he's asking about what he should do with his diet. And he's just sitting there confidently. I know it's complicated, but this is how fat loss works. Let me tell you the secret.

You just need to take my body fat quiz, Joe. So go to vshred.com slash whatever. And it's like, surely people fall for it. You see the ad over and over again. So it's like, that means it's working because he's dumping the ad dollars into it. So I don't know. I feel like that guy needs to change his name and get plastic surgery at this point to avoid the damage he's done to his credibility from people in the industry who know who he

is. And it's just like an at scale, hammer as many people as I can with ads kind of model, which it was interesting that you're served up him so much. Well, it's funny. I haven't even seen an ad for him in months. There was a period when I was getting them nonstop. I wonder if there's a way to like selectively exclude certain demographics or something.

Cause surely knowing that you said he's a huckster and you see his ads all the time and you were starting to say some stuff about him publicly, doesn't help him. So I don't know. I don't know if there's a way to get that granular on the ads, but that's interesting. Yeah, interesting.

Well, my friend, this was interesting. The biggest takeaway for me here is I need to get one of these ninja creamy things. I'm really curious to see if I can up my protein shake into ice cream games, so let's order one of those things right now. Yeah, I'm down. Let's go get you a YouTube premium.

Perfect. Yeah. All right, thanks, man. Thanks for having me. Thank you for listening to this week's episode of The Drive. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members. And in return, we offer exclusive member only content and benefits above and beyond what is available for free. So if you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. Premium membership includes several benefits. First,

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