#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

26 Feb 2024 · 2 h 38 min

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Podcast Episode Summary: The Peter Attia Drive #291

Episode Overview Title: The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more Guest: Derek from More Plates More Dates, Part 2 Host: Dr. Peter Attia Date: (Not specified) Link: [View the Show Notes Page for This Episode](https://peterattiamd.com/derekmpmd2)

In this episode, Dr. Peter Attia continues his conversation with Derek, a fitness educator and entrepreneur from More Plates More Dates. They explore various topics concerning testosterone and hormone therapy, the effects of performance-enhancing drugs, sustainable fat loss methodologies, and the importance of critical thinking in health advice.

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Key Themes and Discussions

  1. Testosterone and Its Role
  2. Mechanisms of Action: Testosterone influences muscle growth and regulates male and female characteristics.
  3. Usage in Women: The complexities and potential risks of testosterone replacement therapy (TRT) in women. Discussion on how TRT is less common for women and often seen as more taboo compared to estrogen therapy.
  4. DHT and Testosterone: DHT (Dihydrotestosterone) has a higher affinity for androgen receptors and plays a significant role in sexual differentiation and muscle growth.
  1. Hormone Replacement Therapy (HRT)
  2. Assessment for HRT: Criteria for evaluating candidates for hormone replacement and concerns associated, especially with testosterone in women.
  3. Clomiphene and hCG: Discusses the use of Clomid and hCG in TRT, along with the risks of using underground sources for testosterone.
  4. Testing and Monitoring: Importance of measuring free testosterone levels and the implications of low testosterone on overall health.
  1. Performance-Enhancing Drugs
  2. Peptides and FDA Updates: Updates on the implications of FDA categorization of certain peptides and their use in bodybuilding and performance enhancement.
  3. Myostatin Inhibition: Discussion on follistatin gene therapy and its potential role in increasing muscle mass, including skepticism about the claims made regarding its effectiveness based on existing research.
  1. Sustainable Fat Loss Strategies
  2. Fat Loss Techniques: Strategies employed by bodybuilders to lose fat while preserving muscle, including calorie restriction, protein intake, and the use of specific supplements.
  3. Caloric Deficit and Protein Intake: Recommendations for maintaining a caloric deficit while ensuring adequate protein intake to preserve lean muscle during weight loss.
  4. Mindful Eating: Encourages a strategic approach to dieting while maintaining satisfaction with food, including the use of diet sodas and high-protein foods to curb cravings.
  1. Critical Thinking in Health Advice
  2. Skepticism Towards Online Health Information: The importance of approaching health information found online with a critical mindset, especially as it pertains to supplements and weight loss strategies.
  3. Influencer Culture: Discussion around health influencers and the marketing tactics used to promote supplements and diets, emphasizing the need for evidence-based approaches.

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Key Takeaways

  • Testosterone Therapy: Is complex and varies significantly between men and women, with potential risks and benefits that need careful assessment.
  • Performance Enhancers: Require critical evaluation; anecdotal evidence should not replace scientific research.
  • Sustainable Dieting: Focus on gradual fat loss and maintaining muscle mass through adequate protein intake and mindful eating practices.
  • Caution with Supplements: Always approach health advice, particularly from influencers, with skepticism and prioritize evidence-based information.

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Conclusion This episode provides deep insights into the role of hormones in health and performance, the importance of sustainable dieting practices, and the necessity of critical thinking when consuming health-related content online. Dr. Attia and Derek stress the significance of tailored approaches to hormone therapy and fat loss, while also warning against the hype surrounding various performance-enhancing drugs and diets.

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For more information and detailed discussions, refer to the [show notes](https://peterattiamd.com/derekmpmd2).

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Transcript

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0:10Hey 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.

0:46If 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 peteratia -md .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 want to have Derek back for round two. In this conversation, we continue where we left off in our first discussion.

1:25We talk about a number of exogenous molecules that impact both male and female health, including testosterone, DHT, DHA, 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, fallostatin, and more. We cover various ways that body builders 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.

2:07So without further delay, please enjoy my conversation with Derek for more plates more dates.

2:17Derek, 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. Yeah. Hence, we're back. And I'm going to do something unusual, which is, I'm just going to tell you, hey, what do you want to talk about as opposed to driving down my agenda? I have a bunch of things that I want to 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 might be some unanswered questions or ambiguity on some specifics when it comes to a good candidate for hormone replacement.

2:53How 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.

3:26I 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 fourth 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 it's a 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.

4:04So 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.

4:40That's neither here nor there. It just is what it is. So maybe let's just talk really briefly about testosterone, antigen 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.

5:19But 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.

6:03And 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 energy 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 endogen 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.

6:39DHT 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 endogeneity, it goes the more masculine and viralizing potentially in women, it could be.

7:18So, DHT is that hormone essentially that drives this pathway to the extreme and is what is responsible alongside testosterone for maximal sexual differentiation, maturation, and adolescents, like I mentioned. But you see mutations in the gene that encodes for five alpha reductase, which is the enzyme that makes DHT, you'll note that certain pseudohermaphrodites 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 10X that testosterone and more DHT subsequent to that and then females much more estrogen proportionally to males, well, somewhat depending on where they're at and their cycle and whatnot.

8:09And then 10X lower this is the australian 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 DHC, 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.

8:51So 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 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.

9:29Right, 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 literal enlargement within just a period of a month. The good news is completely reversible once the dose was restored to the tenth 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.

10:09Yeah, they are depending on their guidance somewhat or very aware of the masculineizing potential of what they're using and some will avoid testosterone entirely because of that because it is essentially equal anabolic as it is endrogenic. So it begs the question, why would you be using testosterone as a female if you're trying to achieve superphysiologic 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, those of the use things like premabullin, sometimes, metanolone.

10:51So, meaning much more anabolic, much less endrogenic. 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 our 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?

11:33Yeah, 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. Wow. Which is crazy. Very high. Yeah. So my mom actually got on hormone replacement a few years back.

12:17And I at the time wasn't overseeing, didn't really check what she was doing exactly. It's 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 that 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 mail, 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.

12:56So, but whatever it was, it was one of the practitioners that promotes 200 to 300 total tests in females, which is insane. Well, might be 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 paramanopause, not only does she experience the predictable drop in estrogen and progesterone, but with it so too goes testosterone.

13:33And 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 -folicular estrogen level, an estradiol level, and took it out of pica grams per desoleter and put everything in nanograms per desoleter, her testosterone as a premenopausal woman would be at least 10 and at times even 50 times higher.

14:16So, 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 desoleter. In other words, those levels exceed even her peak physiologic level. So it doesn't surprise me that that would be the Androgenizing Women.

14:53Do you understand or do you have a sense from the 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 Androgen's feel pretty good if he were just crashed or very low. And then all of a sudden, you're essentially on the male proportional equivalent of like a bodybuilder 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.

15:40And if you're not keeping a close eye on them, they can really, 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, that 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.

16:14So she's sort of in the 10 to 20 nanogram per desoliter 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 desoliter, which is sort of in the ballpark of what would be kind of 70 to 80th percentile for women that age. But then it turns out that she probably was lower than that, because once you get her, her acne is out of control. You would surmise from that that well she must have lived at a lower level and for her 80 is Superphysiologic 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 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 for their confounding that is How many people have been on combined or all contraceptives for like decades?

17:29Yeah, just totally skews everything. Yeah, like I've dated girls So I've seen like 80 % suppression of their hormone levels to testosterone, free testosterone, especially proportionally more so to you because of the rise in the SHPG goes to do. Yeah, it'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. It's like they've never experienced it because they've been prescribed it since 15 years old or 16 years old or something.

18:04So it's tough because it's like, you don't even know what your ideal target is. Even if you were getting blood work off in times, it's totally skewed. And that's something I definitely wanna talk about on my podcast too, is some of that 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.

18:38Have you been following it all the NETESTO product? Looks good if you're willing to tolerate it. Yeah, for folks who don't know, NETESTO 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.

19:17But 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 Cialis 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.

19:57I've candidly had some experimentation with it and doesn't seem to me 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 a effect. No, I would make no difference to me. Yeah, yeah. But you're saying in a female with low testosterone, taking a couple of shots of nattesto, didn't in the subsequent hours have much of an impact on libido? No, but that's obviously, and of one, 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.

20:33I 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 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.

21:16I'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 antihistamine or something? The one I had experienced with was a compounded replica of that. So maybe the Nattesto 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.

21:56I would want to see what the real deal product was like. Let's talk for a moment about DHA. 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 DHA. And I'm not sure where this came from because DHA 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. I'll see you then. That's my point. Yeah. So even across the border with our neighbors that were otherwise pretty similar to DHA. is, yeah, it's casual one.

22:34Yeah. If you have that, you're doing something more illegal than having anabolic steroids. Wow, I did not know it was a schedule one. And yet here it is, go on 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 federine in G &C in Canada. It's like, why? It's literally used to make meth. And then here, it's a lot harder to get a veteran. But then you can get Yo -Him -Bine here, which is a fat vulnerable talk about later, and in Canada it's banned.

23:13Who'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 wanna be on DHA, I wanna be on DHA, and they're 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 DHA 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 DHA does much of anything. What did the data say? I looked in a decade, by the way.

23:46So a decade ago, when I was really beginning to get interested in hormone tinkering, I came to the conclusion DHA 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 whatever backdoor. And yet it's a usada water band drug. It's treated just as testosterone would be or any of it, which is wild. But in females, it actually is useful and can increase testosterone to the degree that 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?

24:38And I found some papers that showed using DHA 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 -eroll 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, because again, combined -eroll contraceptives, there's many different variants you could get, so depending on the brand, you might have a progestin that's more endogenic or one that's less. Ethanolastradial is or isn't included.

25:15That will all vary, but in general, in like the traditional, most sold and prescribed combined neural 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 off the top of my head. So why do you think women would be more sensitive to this?

25:56Probably 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 desk later 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 gonna check that paper out, but that might be a nice thing to have in your pocket if you live in the United States.

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26:33One thing I can say though is DHA 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 DHA for some subjective feeling of well -being There's no real Bio -markers to reinforce that you're deficient your DHS EAS 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 DHA 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.

27:23Remind me, we don't measure DHA levels. We measure DHA sulfate levels, correct? Yeah, that's the only proxy in like traditional blood orc metrics that I'm aware of to test for it. Do you know why I used to know why we couldn't measure DHA directly in blood? I think the majority of it is sulfated. So getting a direct measurement is not as indicative of the total body pool or what. 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?

28:04So 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 Marena progesterone coded 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.

28:44And 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 marina. Why do you think that is? Why do you think progesterone is so important for women? And outside of reproductive standard utility, I think that it's more, like if you look at a steroidogenesis cascade, which is like in the 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, a DHT, and estradiol, and estrogen, and all that stuff, like that is called steroidogenesis, the synthesis of all these steroid hormones in your body.

29:36And 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 -antilitic 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.

30:25So 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 orally 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 allopregnidolone, which is seemingly implicated to some extent in post -finasteride syndrome, but also very much in post -partum depression.

31:04And they've even created a synthetic analogue of it now that they use to treat post -partum depression, which is interesting, but all of those different metabolites cumulatively, if you are deficient in some amount of them, depending on the individuals 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 shutdown state. It's not endogenously regulated the same way when you have feedback mechanism.

31:48So you're kind of just manually shooting stuff at your liver and hoping it's going to 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 that is far less to achieve the outcome they want or much higher or perhaps don't respond at all because that's not what they need depends. But I think that would be my educated yes. Is there a role for progesterone use by men? Yes, I said this last time and you seem baffled and it definitely does not have an approved use in men.

32:29There's no literature that points to it as this is something you should use in man 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 what not. You could 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. 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, ticicular axis, antistus, around through androgen receptors.

33:17But 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 anti -androgenic 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 know how it does it, but it does seem to produce anti -androgen -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.

34:00But if you're on TRT, it 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.

34:45Like 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 test, which is like 20 times higher than estrogen. So if you have that regulatory frame or 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.

35:27And because you have a long, extra compound in your system, you don't have the luxury of endogenous 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 going to diminish to your system until you want to inject again. And a lot of guys, even when they're doing, twice a week or something, you're still getting some level of spike and then dips and then spike and dips, where if you were a natural, with normal natural chutzat's often production, it would be very pulsatile with a diurnal rhythm with natural dips and valleys and peaks and it would not fluctuate where it's like bam, bam.

36:12And 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 and urgent 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.

36:46Your 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 are 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.

37:23I was unaware of that. Do you look at free Androgen Index where you're just taking the ratio of testosterone to SHBGs, 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 lab corpus 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.

38:06And 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 hypo -ganadil men that might have, you need to be a bit more, I don't know, lower concentrations, 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 an immunosci, or a calculation, because it's going to be based on the cross detection of the total test australian presumably as well if you use that.

38:51So 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 lab core run them both. I had them run the immunos assay, which is not the gold standard.

39:26that'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 immunosay 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, Roch ECLIA, right beside it. Yes, a Roch is the company that provides the assay for them. But 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 % difference. I think it's significant enough to justify getting the accurate one.

40:08Yeah. 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 Estra dial. So the Estra dial 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 test thing will cross -detect estrogen synthetic estrogens 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?

40:52And by the way, I see this in other patients as well. That would be tough for me to speculate without seeing the full camera. 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. I'm assuming you didn't take any biotin for ever taken biotin, you know? 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 buy it and put it that way. That would still mess with it.

41:25Yeah, 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 Maricale, which is my team and they don't know of anything either. So I think biotin is the main thing and I think it's excused 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.

42:02Got it. Okay, so let's now kind of shift over to the testosterone replacement decision making in a male. So it seems to me that younger and younger men are seeking out testosterone replacement therapy. Is there any data on that or is it 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 like skyrocketed over the past decade. Where do most men get their TRT? How much of it is done from an enter chronologist, for example, like someone who presumably spent a lot of time understanding the system,

42:47how extreme example. Yeah, it's tough because countries will differ and there's 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. And 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 antibiotics and get some Bitcoin and buy it.

43:30So there's a lot of people that will get it from their gymbroes or online. It's very accessible now. 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 gonna 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 harmonious that will be on TRT underground. So I would say there's probably the majority of them are on not scripted TRT even like lenient telemed clinics 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 -mo?

44:20Are there so many of these around whack -a -mo? Yeah, so there's a lot that Sell an amount of volume presumably that is not 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 two, and sometimes 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.

45:08And 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 an underground lab that is producing it and making what they're advertising as a accurately dose sterile product that is branded under their like underground lab brand essentially. Okay. So for folks that want to do this, then a little bit more of a responsible way and go and see a doctor, there are a lot of these doc 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.

45:46I do believe that a lot of that stuff's 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. anything else you want to say on the Eclomet, HCG, T trade -offs? I think when you are trying to restore fertility in the short term and your reverse -to -injections and there's a lot of factors that could lead me to say Clomet might be viable, but in general if you're looking at something long term I would say typically Clomet or Nclomethian 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.

46:33You are essentially putting yourself in a position of long -term estrogen receptor antagonism in certain tissues, meaning you're gonna be missing out on estrogen receptor activity in certain areas of your body that down the line could manifest in array of issues. Like if you look at the side effects of serms, 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 gotten more data for clomid than we do in clomaphein, which is, as you said, just a very, very close derivative of it. But they both work the same way.

47:08They both block the estradiol receptor of the hypothalamus, correct? Yeah. And then the zoo clomaphein component of clomid has two drugs, essentially, in it, because they will have differing effects. That component of it is more anti -genadotropic, I believe. So it's like the end -clomophine component is far more specific to the serum activity you are seeking in the hypothalamus. The zoo -clomophine 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 clomophine, 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.

47:50I 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's better now, but at the expense of literally tricking your brains through inhibiting very very necessary mechanisms.

48:34So 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 and serum, but it's not perfect. As we talked about last time, you were going to get, we could just Google Clomanside effects and you'll see an array of different things, I believe, including but not limited to skewing of lipid parameters, do you have the one who taught me about, you know, it's a Yeah, I like that sketchy.

49:18I 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?

49:5450 milligrams daily, 50 milligrams three times a week, around 50. Obviously in the bodybuilding world, I told you both the absurd PCT regimens, post -cycle therapy where guys are using a hundred per day for shorter time frames. is but it's superhydosis. I think we're going to see a big increase in the use of clomid and e -clomid 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.

50:35Whereas, via telemedicine, you could still use clomid, or potentially e -clomid. So that just sort of suggests that we're going to see HCG 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. But 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?

51:13Oh, 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 while 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, et cetera, et cetera. 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?

52:03So 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 wrong, you could determine from there why are my testes not responding to it? I mean, Comet 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. That'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 testies to this signal from your brain.

52:47And if you're 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, Choreonic Genetotropin receptor, which initiates the light excelle stimulation and intertasticular 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.

53:34So 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 hypogonatism 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?

54:23Or 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 hypercordislemia, maybe not so great. Training, overtraining, under -training. Like, what are the things you would look at to brainstorm if that scenario were the case? I don't know if that's the case, by the way, but that's an experiment that probably worth doing to see, hey, why is my T low?

54:57Is 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 a HCG to even figure out, you know, what's my response at the test season 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 Gennadotropins 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?

55:41I'm not gonna say a lot of people over -trained 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 intake's not being adequate amounts, magnesium intake's 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 a hundred plus nanograms per desolate or potentially depending on how deficient you are. So some of these low hanging fruits with the sleep, micronutrients, minerals, actual macrointake, some people are eating ultra garbage processed foods, no micronutrient density, they're under eating, maybe they're on semi -glutine, they're super calorie deprived and they have very little protein or something.

56:27That'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, get out of trope and 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 out of 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.

57:22Like I would love to just say everyone's testes are going to retain perfect function forever. That'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 measure that, but presumably that may be low, or the receptor response to the GNRH is suboptimal too.

58:01Yeah, interesting. So it's like a whole upstream. 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 casrating 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 romanticize the estradiol, that was a meaningful impact from inhibiting its negative feedback to begin with.

58:37At least with a GNRH agonist, I know I'm maximally stimulating petuitary output to whatever capacity it is. With Clomid, I'm just inhibiting negative feedback to whatever suboptimal capacity my ER is agonized. Yeah. 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 It's a pituitary output potential. You would use a GNRH agonist and see what happens.

59:12Is there one out there? Gnaterelen 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 yeah, they exist. It's interesting in that the question is, what's the so what, right? 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.

59:58Well, 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 microadnome. 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. Yes, sometimes you'll have like a prolactin secreting at a nomen too 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 What about this you just have to find as good of a medical provider as possible?

1:00:47I 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. 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?

1:01:22What'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 want to say on TRT before we kind of pivot to something else? Yeah, I guess just to put a bow tie on the whole natural simulation thing I do think if you are Mindful of fertility. It's worth consideration of 8 CG 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, wanted to have a child, realized the arduous recovery process was like pretty significant.

1:02:06Are 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, the longest I could find was four and it seemed to be pretty reliably restored but there are some that just doesn't seemingly. So you're saying someone is 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 gonna take super physiologic trend. It was like, you guys abuse some amounts of synthetic drugs and a binge -shot down.

1:02:41And to rescue these guys, they were using recombinant FSH and HCG and megalosis. 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 control things, but it's very difficult to control for illegal, leased drugs at abuse of dosages in random bodybuilding 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 a hundred percent Okay, when we last spoke we talked about a whole bunch of peptides Just recently, meaning after we spoke, but the last discussion.

1:03:51The FDA came out and took a list of about 30 peptides and put them on a list called Category 2. Now this included six of the peptides we discussed, including BPC157 and what is it, CJC? CJC1295. IPAMRL and 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 two 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.

1:04:32And 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 a advisory a realist 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.

1:05:21And 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 commonality 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.

1:06:05I feel like it might be scenario like that. When you look at these research chemical sites, they are no different than they were months ago. These are the same sites that have been operating with Tursudo 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 Ali Baba 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.

1:06:49If you want to call 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 of 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 as 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, money, Graham, Western Union, and stuff like that, typically crypto.

1:07:30Yeah, some companies do credit cards too. So the rationale for putting these 30 peptides on this category two 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'm trying to understand what's being communicated in this ruling with respect to these peptides.

1:08:03I think publicly what they're saying is it's a safety concern and there's no actual FDA a pervalt 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 Melano Tantu 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 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 and then compounding pharmacies, the ones that are willing to risk it for the biscuit, well, you know, make a certain amount in quantities that they deem is enough to satisfy the perceived demand, but not enough to get whack -a -mold potentially.

1:08:54So 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 other similar mechanism of action or whatnot. And you could find a catalog of Frankenstein compounds that a pharma company didn't want and and get it from China and then do the whole process over again, because there's endless amounts of those.

1:09:33Why 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? And 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?

1:10:16I 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 that. 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 GHRH analog. So it works quite well in conjunction with growth hormone releasing GH -secreted hog that will essentially enhance the output of growth hormone concurrently.

1:11:00So it's not bad. It's 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 approved for lipodistrophy and presumably it's still going to be prescribed and sold. I don't know if they're going to climb 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 Agripta 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 the day. But that will continue to be prescribed. And BPC157 was kind of a VED Jeff analog.

1:11:34Yeah, that one is 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 trial. 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 myostean or does this or does that.

1:12:11You 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 girl 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.

1:12:53That's part of the thing that sort of fascinates me as 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 VED Jeff, that's probably it. And let's compare that to a placebo and actually see, are we getting quicker recovery?

1:13:29And 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 but they've clearly had enough of kind of the Wild West. Yeah, I do wonder what really brought it to the retention if there was some like, it must have been our podcast. Yeah. There's something presumably that brought to the retention. This is being, I don't know, mass marketed misuse. 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.

1:14:05So 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 ergo genica 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 humans play out. Now granted, if they got halted in trials, probably wouldn't have ever happened anyway.

1:14:42So it's just random people taking it. But yeah. 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 fallestatin. So for folks listening to us who haven't been following this, I guess there's 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 fallestatin. That makes more of the fallestatin protein, which inhibits the expression of the myostatin gene or maybe inhibits the protein myostatin, one or the other.

1:15:25And 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? 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 you want to just tell people what a myostatin knockout looks like? It produces a double muscle phenotype. It's what they call it. And if you look at these catalysts, like you would think it's Photoshop by how absurd it looks.

1:16:03This is like the Mr. Olympia of cattle essentially. 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 to 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. Forget what type it is, but she has the same miles. So my roommate and I spent the rest of medical school just talking about we've got to figure out a way to get a myostat and then yeah.

1:16:40Okay, 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, but you can get a gene therapy that will activate and produce more of a protein called fallestatin that inhibits myostatin. 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 Fallestead administration does enhance muscle, like it does happen.

1:17:21And I guess as a result of that, a lot of these research chemical companies were very quick to come out with freeze -dried, lifelized Fallestead and product that had 1 milligram per vial and you would buy it for hundreds of dollars and then you would basically like 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.

1:18:01So you've got this kind of gray market, Follestat and product out there. Yeah, and this one is not gene therapy to be clear to you. It's literally just... Yeah, no, you're actually injecting the project. Yeah, yeah. So you'd literally get bacteria, static water, shoot it in, switch it around until it's mixed and inject it in yourself. And the half life is like, I don't know, a couple hours. So you'd have to inject 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.

1:18:35There'd be the random outlier. He's like, I gain 20 pounds in two days. and so you're 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 is one in humans, I believe, two. 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, Biohack, or dude, and got it and I have yet to see any actual metrics before and after muscle growth or anything of that nature, he's kind of just produced apparently his fallestatin increased.

1:19:18So presumably it's actually doing something. It's just that outcome of more fallestatin actually binding enough myostatin to have an effect that is worthwhile. By the way, how is fallestatin measured? Is there a certified assay for measuring fallestatin? I don't think so. I think they're using their own internal measurement as far as I know. So they have their own assay that they've developed. So I don't really know. There might not be a validated assay for measuring this hormone, but this protein rather. Yeah, I couldn't say for certain that it's actually measuring it correctly. So assuming that it is, it is increasing it.

1:19:53And 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.

1:20:31because 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, you want to say cheat day, I mean, just the day you go off the rails and eat whatever junk you want, where you had horrendous distension 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.

1:21:05So I'm 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 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.

1:21:44So 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 vasoconstricts from the cold. So that is something that is very abused in the before and after kind of transformation shots where they will achieve transient look that is not representative of them walking around and is certainly not representative of the complete opposite circumstance that they do the before shot in.

1:22:25So 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. You'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 and depending how egregious you wanna make it, you go in much worse lighting, after you have successfully downed four to 5 ,000 calories of processed garbage food.

1:23:05So you actually are swelling, you're so inflamed. Yeah, think of everything you could do to look at her in this is 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 was just like exaggerated plus you're descending 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.

1:23:36There's a lot of things that it sounds like these factors are not significant enough to make this big of a difference, but 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 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...

1:24:10Well, 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 that 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.

1:24:47that 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.

1:25:30Yeah. 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. 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 what did 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.

1:26:07You 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 your... There is none. Okay. I know. 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 the control 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.

1:26:45In 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 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 basically completely knocking out myostatin.

1:27:33Whereas 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 fallestatin 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.

1:28:08Apparently there's a phase two trial that is happening either in Canada or Japan and then there's six month results that are more impressive that they're highlighting. So and these phase two studies are specifically for sarcopenia. So I am assuming they're recruiting people over 60. Look if you could add five or ten 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.

1:28:46To 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. Yeah, no for sure. 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 fallist at work in humans and produce an outcome that is something you could avoid antibiotics entirely for the endogen sensitive that might otherwise need anti -catabolic action in later life or in a burn scenario or whatever.

1:29:33Like that seems like pretty useful to flesh out because Saram's definitely didn't pan out the way farma 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. Rest and 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 fallestatin, when I was looking it up, I kept seeing the FSH inhibition statements.

1:30:12And 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 is something that apparently the isoform using this vector is one that is less specific for that component of what fallestatin and 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 I have no idea what would be causing it.

1:30:54Well, 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. And, notably, there are some big names they're using, 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 gotta 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.

1:31:24If 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 But 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, like this is why I pay for your membership is like the trust factor I have in your stuff is like above and beyond any piece of content I consume essentially.

1:31:58Like there's no bias, there's no financial incentive, even to the degree of you don't push companies you're an investor in, like it is just legit, facts, totally unbiased. Here is Peter's opinion with no incentive inherently manipulating my opinion whatsoever. So 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.

1:32:37And I think the purpose of the video is, hey, for 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 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.

1:33:20Those are the metrics once you get to the end of a dieting 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.

1:34:02I 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 that latent sugar bomb dessert. Like 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.

1:34:42So that is something you'll 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 replace 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.

1:35:25One 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 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, but 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 yokes in, get your micronutrients, but it almost tastes indesernably different when you have just maybe like one or two of them replaced with egg whites as opposed to the whole egg.

1:36:14There 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 in itself, just even three things I mentioned, you probably could have chopped off 500, 600 undercalerage. 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.

1:36:47This 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 from my channel too. It was 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 gonna feed your family for more than a year.

1:37:26See, 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.

1:37:59So 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 cost 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.

1:38:35But also, I truly believe rifle hunting is more humane. A person who's a really good shot, believe me, 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. Well, that would not be a terribly expensive proposition. Now, maybe the first year it is, but remember, you amortized 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.

1:39:10Definitely 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 podcast, 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 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 developed 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.

1:39:45and now taste 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 worth a while 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 going to refeed when they're done.

1:40:20And 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.

1:41:01Oh 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 diced 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 body builder, 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 on what level and how on track they are, but some of them are starting at like 12 % body fat.

1:41:38Everyone has different goals of what they consider good. So maybe this is like my skewed fitness perception saying 10 -week -o 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 titrating 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.

1:42:28So what they do on the last week, doesn't really count. Okay, okay. Up until a week out. But up until a 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 like I've seen the macros on your venison and it's... Yeah, 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 as 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.

1:43:13It's 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 if you ate that diet, it wouldn't go up or down.

1:43:53What 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. Eat exactly this every day and then see what the average is at the end of the week because just going by 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.

1:44:26I'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 a magical standpoint, perhaps fertility, it's even used for depression now in women out like 10 plus grams or something, which is crazy. So a lot of use cases are coming out, but overall we all know it works for muscle, for performance in the gym, as well as volumizing the muscle.

1:45:01Would you say creatine is hands down the best over the counter supplement for performance? For sure. Can't think of anything of 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, yeah, 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 somebody in your mouth, you count it regardless of its a sauce, regardless of its a drink, regardless of its a lick You count that shit.

1:45:40Do 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 gonna 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 it can just write it down quick. You don't have to go look up and cross reference.

1:46:12You 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 getting 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. You want to kind of like, titrate it back up a little bit.

1:46:42But 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. Because ideally, and this is kind of the whole general approach without getting weight 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.

1:47:22Carbs 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?

1:47:59I 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 for sure if not more Yeah, so unless you're Brian Johnson or willing to get like 25 % of your calories from oil Probably not a bodybuilding conducive Macarolot mint even though fat is satiating its nine calories.

1:48:50Yeah program 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 a silly am 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.

1:49:25and 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. 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. Cause when it comes to actually describing the nutritional literature, I hated as much as you did. It's not like something I like to talk about. Oh, how much fiber should you keep in? I don't know, man.

1:49:57A decent amount. It's 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 body building space is modulating carbs up and down accordingly based on needs in the gym and protein stays at an amount that is anti -catebolic or conducive to muscle protein since the system is 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 while you're rising the muscle having glycogen topped out, etc.

1:50:32And from there, I would typically recommend a 300 deficit and literally milk that in that week prior to show how many calories is a bodybuilder typically down to. If they're stayed 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 IFB 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.

1:51:14It also depends how much they're willing to lean into cardio because some guys will actually prefer to just diet themselves into the body fat and not do any cardio because they just don't like it. 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. it. So what we see even in like the IFBB with these top bodybuilders 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 metforminic controlling blood glucose, like they're actually making sure they are moving around and actually shuddling nutrients as much as they can even outside of the gym.

1:52:08Some 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.

1:52:50And that's in enhanced ranks that guy's eating exorbitant amounts. But anyways, back to the blame in general, you're in a 300 deficit. You kind of milk that for all you can. And by that I mean, And 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 Thorma genesis, which is like fidgets and moving with just like your everyday activities.

1:53:32You 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 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 is essentially a malnourished state.

1:54:26Because if you push too hard and you go from, let's just say you're eating 2800 calories a day and you instantly dropped an 1800, 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.

1:55:04And then from there, because as a 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 the expenditure side. Try and do what you can in a titrating 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.

1:55:37So if I was doing a seven to ten day water only fast, which I was doing once a quarter, the change in hormone levels after seven to ten days of nothing was profound. So if my testosterone started out at 5 to 600, it would probably end at 1 to 200. Total T. If my TSH was 2, it would go to 4, maybe even higher, maybe even 6. But free T3 and reverse T3, if free T3 was 2 and a half to 3 and reverse T3 was 12. So the higher the free T3 in the lower the reverse T3, the better thyroid function you have. Post -fast, that free T3 would go maybe from three down to one and a half, and the reverse T3 would go from 12 to 32.

1:56:27Yeah, 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 what your gonadotropin was did when you went back to normal dieting at that point and then how you responded from there, because if you could see 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?

1:57:04Not 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 divine. The ninja's like the blender. Yeah, but this one in particular is very popular lately because of the consistency of ice that it creates. What's it called? Ninja Creamy, like C -R -E -A -M -I.

1:57:41So it's not the 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 way isolate, plus some non calorie fills like sweetener. If you want to risk it, maybe some sugar free putting mixture in there too, like a chocolate or something.

1:58:15And 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 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. 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 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 different one before.

1:58:54or another one I used to put in like huge amounts of ice fruit, you could do fruit too 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, what I'm gonna use is real simple. I'm going to use almond milk or cashew milk.

1:59:27So it's my wife calls them nut juice. Yeah. Like a way protein. I'll typically mix the unflavored promix. Yeah. Do you know that brand? No. Prometheus, I think it's maybe I'm getting it wrong. Anyway, it's unflavored way, high quality way. 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.

2:00:02So I 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 macros, 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.

2:00:34That'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 tequila sticks.

2:01:07Like 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.

2:01:39I'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 it in a microwave and cook it and it's still high quality food. Okay, so let's talk about some of the fat loss from a copious.

2:02:10So I have friends that swear up and down by carnitine, Elkarnitine, I think they inject it. So tell me about that. Elkarnitine is present in red meat and depending on your diet, you may or may not be deficient in it. And it is, some of 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 animal stimulation, actually increase the expression of what you can get out of your testosterone input.

2:02:50So this is the main reason why people, I know use it and presumably why a lot of people use it that. You know too, it's often advertised as get more out of less endogen, 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 super. So similar to creatine, you can make the argument that endogenously or through your diet, you may be 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.

2:03:28And this is something you inject sub -Q daily? Depending on the volume, because it is, depending where you get it, could be 200 milligrams of milliliter, 500 a milliliter, and you can only put so much water -based sub -Q before you have lumps. So even though it's more easily absorbed, it's still not something you want to be injecting milliliter of. So we're 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, home brew sometimes.

2:04:02Home brew, how are they sterilizing the water? And I'm not a chemist, he's gonna 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, yeah, 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 great, but like compounded versions that are made in an environment that's been at least fact -checked, depending on the rigor of the pharmacy and question, of course, because you've done deep dives into compounding, which I recommend people check out.

2:04:39I 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 If legitimate FDA -approved molecules like cortical steroids 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.

2:05:18So 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 quarantine 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 colion, 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 up regulation, which is still like a fringe thing you're seeking that may not be ultimately founded.

2:06:14you 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 circumcinct. Some people use Allison 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 a fringe application with a hopeful outcome that I guess you can measure and serum your TMAO before and after Alice and verse not and see if there's a difference.

2:06:50Are there any clinical trials that demonstrate any efficacy of injectable or oral alkanatein? With carnatein, the results are mixed. Some of it looks promising and then some of it doesn't. So, 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. 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.

2:07:27I'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. So 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 lesser 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 a people claim and seems to be at least somewhat reproduced anecdotally.

2:08:01But that's speculative. If I would not hang my hat 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 fabriner 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 increase 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.

2:08:41So as you enter into nutrient deprivation territory, it becomes a lot harder to even move subconsciously, let alone, actually fuel your everyday activity. So I'm not to say you should become a caffeine addict to support your deficit. That'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 like special circumstances.

2:09:24You mentioned, you know, him being earlier. Let's see more about that. So that is a alpha two adrenergic antagonist. When it comes to some of these adrenergic type receptors, it gets kind of confusing. Even though it's an antagonist of the alpha two receptors, it will have stimulatory effects, but contradictory to what you'd expect from a stimulant, it's not vasoconstrictive, the same way you might get from a emphetamine or essentially any other stimulant that works well. So this stuff raises adrenaline signaling very significantly and there is 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 Expending 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.

2:10:33Yeah, so like it feels much more racie and aggressive than caffeine. How does it compare to like a fedron? A fedron, I believe, is a beta -2 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? Yo, Him blind half life. Can't recall off the top of my head, but it's relatively short. But is it the type of thing that people take for the workout when they're in calorie deficit? Typically, you would take it before cardio or before training is the typical application.

2:11:15but interestingly enough, it's also used as an afrodiziac and can enhance erections, which is weird. You wouldn't expect that from a stimulant. And also, 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? Cause 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 witsend 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.

2:12:16So 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 overnourished or undernourished or adequately nourished? Are you adequately muscled or undermuscled? 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.

2:12:54Now 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 hyper -cortisolemia 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.

2:13:45There are certain things we can do. You can use ashwagandha, you can use vasvatidol serine. 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 two receptor antagonists, you know, him buying an alpha, you know, him buying, 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 hypercord of the solomy me. That's right.

2:14:18That'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, 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 to then something else that might be where you would look. But anyway, that aside, as far as actual anti -catebolic 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.

2:14:54And that's where they get their anti -catebolic action in 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? Oxandrillon was also scheduled, just band altogether, what's the status of it? So my understanding, and I may be not entirely correct, but it was FDA approved for many indications. and then basically the FDA determined based on and this seemed like kind of a nonsense thing, but a meeting in the 80s where they determined that antibiotics in particular antibiotic extension had no efficacy anymore, essentially.

2:15:48And 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. 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 Anivar, which is the branded version of our general.

2:16:24Yeah, so Anivar is made by a pharmaceutical company and I'm referring to Oxandrolone, the chemical, not anavar. Understood, but they're speaking to the molecule, not the branded drugs. Yeah, my apologies. Sometimes it's easy to conflate what the layman speak for these anabolic system. But I'm just saying, then it doesn't really matter who makes it. Isn't this ruling directed towards not just the company that makes anavar, but even a compounding pharmacy that would make Oxandrolone. Yes, so they are saying that there's now no approved views 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're Can somehow lean on a I guess the time and 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 our Xander alone for years and it's got great results can they override that for exemption?

2:17:26I thought you would feel that 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 Oxanderin, which was what I know to be, what used to be Anivar, which was sold multiple times.

2:18:05And Oxanderin is taken, SL, it's taken out of the tongue, right? If you get a Trosi from a compounding pharmacy, you could get a sublingual format of it, but it's typically a press 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 -alculated anabolic 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 a superior hepatotoxic outcome where it's not nothing, but it's lesser than oxymethylone anodrol or like, you know, wind straw or some of these other ones.

2:18:49Or stenozole. Yes, stenozole was injected, right? That's typically taken orally, but it's also injected in water -based, 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.

2:19:33And I said in order, it was like drugs and then diet and then training. I don't even remember what the order was 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 antibiotics without the support of a great infrastructure of diet and training and sleep. So, as much as it could be a bandaid for shitty, all those things, you will achieve a fraction of the results even on anabolic, if those are not in check.

2:20:14I've even done it myself as much as I don't wanna 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 hyper -responder 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 fill -heat 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 antibiotics, but like it still doesn't exist without these things.

2:21:00Has someone done the study of testosterone replacement therapy be 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 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.

2:21:48Two 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 a 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. Yeah, so you almost need to see that on 100. You also have to drive 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 to this better than me, unquantifiable by standard metrics of measurement to body composition.

2:22:36Because ultimately the way these work is not just through the production of muscle protein synthesis and contractile tissue. It's also like the increased intracellular water that you would not hold otherwise and the increased blood volume and increased 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.

2:23:17But I think it's unquestionable that anabolic, 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, you're 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?

2:23:59We've talked about him briefly Gary Breka He has a lot of good information don't get me wrong. I don't want to turn this into a shooting on him parade necessarily, but the guy very heavily emphasizes the importance of getting gene testing for a limited amount of snips that are ultimately very common to find in general population, and then making wild extrapolated claims from that that assert all of your ailments 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.

2:24:41If you have your homozygous for C677T, MTHFR, which I am, and a lot of people are almost everybody. 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 actually sells it's like, is a $140 ,000 red light bed. Does that improve methylation?

2:25:21I 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, objectively. Borderline, you're in a low -end exotic car territory essentially for a fucking bed that emits light on my face. So a bit skeptical and then he has other stuff, but in particular his gene Testing how much does the 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.

2:26:13Either 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 known that MTH of our stuff is also in your, yeah, it doesn't cost anything. So I mean, $600 seems a lot given that so you can do a whole genome sequence now. Three billion base pair. We're not talking snips, whole genome sequence for $300 today. That's crazy. I don't know, man, but then you get his, you know, interpretation of it, which is...

2:26:47It almost feels like he's hoping you have one of the most aggressive methylation impairments 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 Sammy or whatever. I feel like even if you are right, you got a needle in the haystack because there are so much that goes into genetics that is beyond these maybe common snips that have some impact.

2:27:23Like for example, if I'm the most methylation impaired, sure, I'll look at B -Tan or whatever to lower my homocysteine, like totally reasonable, but like don't assert it's the root of my everything I'm wrong with me, or I don't know, 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?

2:28:03Yeah. So if you have a gene mutation, or if your 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 actual medical condition he has, saying you have the answer and it's your 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. It absolutely most certainly is not.

2:28:37It's a series of enzymes called diodenases that make those conversions. And to my knowledge has nothing to do with your MTHF -R gene. Yeah, Chris Masterjohn had a really good video recently that kind of summarized it I would recommend people check out his stuff if you want to know anything about methylation. You've had a lot of fun. Yeah, I've been 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. Do we talked about free -fade Johnson the liver king?

2:29:08Other Brian Johnson the vegan king, I don't know. He doesn't have a naked name. Two 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 fallestan thing. He's done a tons of stuff. He's on telemere link thinning peptides. He's on thymus regeneration enhancing peptides. ones that are all banned now based on the thing or at least category two.

2:29:44I don't only have ever seen somebody 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 monoxyl at two and a half milligrams, which is super outdated anti -hypertensive 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.

2:30:20Granted, no one else is doing it. So it's interesting, but I watch with skepticism about what is going to come of it. And if it's going to become this monetary incentivized hype train, or if he's just going to 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, because I have my YouTube premium, so I don't see it. Yeah, you gotta get on that, dude. Did you do it last night? I didn't do it last night. I don't know what you gotta do. I didn't do it last night. What does V Shred do?

2:30:54He, it's like how do you know 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. Oh yeah, yeah. Yeah. 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, and 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.

2:31:27Yeah, 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 like to give this 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 X X 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.

2:32:02You're thinking there's no way I'm going to buy this shit. you just want to find out what he's going to 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, 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.

2:32:33The bottle costs more than the ingredients. That's how bad it is. But he's giving us a discount because we made it through the video and we're clearly. So instead of 140, you'll get it for $99 .99. Yeah, but on subscription. On subscription. 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 unbelievable. That was unbelievable. I don't know if Joe Cena 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.

2:33:08Oh, 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 like 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 v shred .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 I need 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.

2:33:49And it's just like an at scale hammers 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 non -stop. I wonder if there's a way to like, selectively exclude certain demographics or something, because 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.

2:34:26Yeah. Well, my friend, this was interesting. The biggest takeaway for me here is I need to get one of these Ninja creamy things. Yeah, I'm really curious to see if I can up my protein shake into ice cream game. So let's order one of those things right now. Yeah, I'm down. Let's go get you YouTube premium. Perfect. 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.

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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.

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