#291 ‒ The role of testosterone in males and females, performance-enhancing drugs, sustainable fat loss, supplements, and more | Derek, More Plates More Dates Pt.2
Episode Stats
Length
2 hours and 38 minutes
Words per Minute
181.95743
Summary
In this episode, we continue where we left off in our first discussion. We cover a number of exogenous molecules that impact both male and female health, including testosterone, DHT, DHEA, progesterone, clomid, HCG, and more. We also discuss some updates from the FDA since our previous conversation that impact the use of peptides. We cover various ways that bodybuilders will lose fat and weight while maintaining muscle, including the various weight loss drugs that are available.
Transcript
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Hey, everyone. Welcome to The Drive Podcast. I'm your host, Peter Atiyah. This podcast,
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my website, and my weekly newsletter all focus on the goal of translating the science of longevity
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head over to peteratiyahmd.com forward slash subscribe.
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My returning guest this week is Derek from More Plates, More Dates. Derek was a guest back on
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episode number 274, which aired in October of 2023. In that episode, we didn't cover nearly as much as
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I would have liked, so I wanted to have Derek back for round two. In this conversation, we continue where
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we left off in our first discussion. We talk about a number of exogenous molecules that impact
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both male and female health, including testosterone, DHT, DHEA, progesterone, clomid, HCG, and various
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peptides. And we also talk about some updates from the FDA since our last conversation that impact the
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use of peptides. We also touch on myostatin, folistatin, and more. We cover various ways that
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bodybuilders will lose fat and weight while maintaining muscle, including the various weight
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loss drugs that are available. As a reminder, Derek is a fitness educator and entrepreneur
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behind the More Plates, More Dates YouTube channel, podcast, and companion website. So without further
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delay, please enjoy my conversation with Derek from More Plates, More Dates.
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Thanks for having me again, Peter. I appreciate it.
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Yeah. So last time we spoke, we covered a lot of ground and yet somehow at the end of it,
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we felt like there was still a lot to talk about. So hence we're back. And I'm going to do something
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unusual, which is I'm just going to tell you, Hey, what do you want to talk about as opposed to
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driving down my agenda? I have a bunch of things that I want to talk about, but curious as to where
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Yeah. I think that a lot of stuff we covered at a surface level,
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and maybe there might be some unanswered questions or ambiguity on some specifics when it comes to,
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am I a good candidate for hormone replacement? How would I assess that? Should I be worried before
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I get on it? What kind of things should I look for? I feel like getting clear on that might be
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worthwhile because a lot of people are kind of in that boat where they don't know who to trust.
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They don't know who to listen to. And I know even yourself, you're kind of like teetering on the
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thought of maybe exploring it. So I feel like even seeing what your thought process is going
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into evaluating, is it viable for you? Would be super valuable.
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Yeah. So let's maybe back up a little bit and give folks a quick primer on the topic.
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So let's just start by just talking about testosterone. I don't know if it's just that
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I'm more attentive to it or there's truly been an increase in marketing efforts, but it really seems
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like the last decade and presumably it's also just the explosion of social media and more channels
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through which this information comes at you. But clearly there's been a lot more attention
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brought forth to this idea. And it's very interesting because there's historically been
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kind of a negative connotation associated with testosterone, natural hormone. We can talk all
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about that, but of course its role as a drug of abuse in sports has sort of tarnished it in a way
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that we don't see on the female side. So when we talk about hormone replacement for women with
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estrogen and progesterone, that doesn't come with the same performance enhancing benefits.
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Which is odd, eh? It's viewed as such a taboo thing, even though at the end of the day,
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Right. And so it's interesting, of course, that estrogen and progesterone are not scheduled
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drugs. They're hormones. You prescribe them without any limitation. They're unscheduled by the DEA.
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Conversely, testosterone is scheduled and much more highly regulated. And again,
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the suggestion here is that there's potential for abuse that we presumably don't see with estrogen
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and progesterone. That's neither here nor there. It just is what it is. So maybe let's just talk
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really briefly about testosterone, androgen receptors, how they work, the role of DHT, and what
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this does for muscle protein synthesis. Maybe just a kind of quick background on that.
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Yeah. So in general, most people are aware of testosterone as the primary masculine hormone,
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but in reality, it's produced in significant quantities in both genders, just proportionally
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more so in men to the magnitude of 10X that of females, I believe. And also both men and women
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produce estradiol and DHT as well. They just have differing proportions and binding proteins and whatnot.
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But at the end of the day, the action in the body is the exact same. It still binds to the androgen
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receptor, induces gene expression, and causes muscle protein synthesis and other anabolic actions
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in bone, psychoactive effects in the brain, etc. And just the magnitude to which it happens
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differs between sexes. And it also is what essentially determines how you sexually mature
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and differentiate as you enter adolescence. So you could realistically manually manipulate
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it too. And you see this in sport, doping scenarios, bodybuilding males, you see it all the time.
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So ultimately, this is the primary androgen that dictates muscle growth and anabolic activity in
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tissues. And the metabolites of it regulate a bunch of other things in the body, which we could get
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into. But to keep it like high level simple, it is the main primary androgen that men and women alike
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rely on just that differing amount. I can't remember if you and I talked about it on our
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previous podcast. I know it's been discussed on the podcast. We'll link to it in the show notes where I
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go into great detail mechanistically about what happens when testosterone binds to the androgen receptor
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and how that gets into the nucleus and how that impacts gene transcription into translation for
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protein. What's interesting, of course, is that you did mention DHT. DHT has a significantly higher
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affinity for the androgen receptor. Anything else you want to say about the role of DHT versus
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testosterone? And we can just talk about it in one gender. We don't have to necessarily break it down.
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Yeah. So the spectrum of, I said androgen, I didn't really elaborate what that even means.
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As far as I know, the definition is essentially to be male or to make male or something related to
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masculine characteristics ultimately is kind of what you derive from androgens. And the further
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on the spectrum of androgenicity it goes, the more masculine and viralizing potentially in women
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it could be. So DHT is that hormone essentially that drives this pathway to the extreme and is what is
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responsible alongside testosterone for maximal sexual differentiation maturation in adolescence like
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I mentioned. But you see mutations in the gene that encodes for 5-alpha reductase, which is the enzyme
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that makes DHT. You'll note that certain pseudo hermaphrodites who don't have DHT will end up lesser
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developed in the masculine spectrum than normal functioning human with full DHT production. So this is
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kind of like an example of the spectrum of on one side, you have males producing 10X the testosterone
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and more DHT subsequent to that. And then females much more estrogen proportionally to males. Well,
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somewhat depending on where they're at in their cycle and whatnot. And then 10X lower the testosterone
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and also much less DHT. And this ratio of androgens to estrogen essentially is what dictates,
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are you going to have male characteristics or female characteristics? And how much are those
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characteristics going to get exaggerated? Because even if you're a full grown female,
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if you expose yourself manually to these hormones, you could very much push yourself in that direction.
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So DHT, a lot of people know about it for its responsibility and what it does for hair loss,
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the common side effects associated with it. But it is an important hormone that does regulate
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how masculine you become as you grow up. So I think that's the best way to put it.
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And there's a critical window of exposure too. So embryologically, obviously exposure to
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testosterone and DHT have an enormous impact on sexual differentiation later in life. I'll give you
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an example. I have a patient, female patient who's on testosterone and she accidentally for a period of
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about a month, didn't read the directions correctly and was taking 10X the dose.
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And that's not that hard to mess up. It's very easy to do. This is something you have to be very
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careful with because the doses are so, so small. And there's no FDA approved women's testosterone as
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well. Right. You could have it compounded in theory at a lower concentration, but regardless,
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she for about a month ended up taking 10X the dose, which means she was taking a male physiologic
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dose of testosterone. The symptoms immediately said, there's something going wrong here. The first
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symptom interesting that she noted, I would have expected hair growth to be the biggest issue. It was
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clitoral enlargement within just a period of a month. The good news is completely reversible once
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the dose was restored to the 10th that it should have been. I don't really follow bodybuilding
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closely enough, but I assume that female bodybuilders are routinely using doses of that nature.
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Yeah, they are depending on their guidance, somewhat or very aware of the masculinizing
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potential of what they're using. And some will avoid testosterone entirely because of that,
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because it is essentially equal anabolic as it is androgenic. So it begs the question,
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why would you be using testosterone as a female? If you're trying to achieve super physiologic muscle
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growth, you kind of know in order to push it to that extent, you're probably going to end up in male
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characteristic territory. So oftentimes they will defer to compounds like oxandrolone, which is
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anivar. They'll use things like primabolin sometimes, metenolone.
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So meaning much more anabolic, much less androgenic.
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Yeah. So these are synthetic compounds that have been manipulated to be more tissue selective,
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as in more anabolic activity relative to the male viralizing component. Unfortunately,
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you can't segregate the two entirely, but they do what they can. And the best thing they can do is
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keep an eye on the side effects as they manifest in very, very real time, keeping a close eye on it.
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I know some women who even have a decibel voice recorder and they will monitor if their tone is
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getting lower or not. Is that potentially an irreversible change if voice is changing?
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Yeah. So you have to be super careful, especially even in TRT. If you were going to do TRT as a
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female, a lot of the clinics nowadays will advertise and market testosterone in a way that is
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highlighting how great it is for libido, quality of life, glucose management, muscle growth.
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Like there's a lot of things that sound attractive about it that are an easy sell to a female who
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may be asexual and like perimenopause or something. And I've seen standards being promoted as cookie
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cutter. Everyone should have a 200 nanogram per test liter total test. Wow. Which is crazy. Very
00:12:10.860
high. Yeah. So my mom actually got on hormone replacement a few years back and I, at the time,
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wasn't overseeing, didn't really check what she was doing exactly. I just kind of trusted that the guy who
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was prescribing, he was very experienced and credentialed and seemed like somebody who I would
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go to myself to ask for a verification. Is this like a protocol? It makes sense.
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And within just a couple of weeks, pick up the phone and I almost don't even recognize her. I'm
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like, what mom? It's skewing in the direction of male blatantly, but she couldn't really tell.
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And what dose was she on? I don't remember exactly what the dose was because it was like a cream and
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the compound in creams can vary, like you said. So, but whatever it was, it was one of the
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practitioners that promotes 200 to 300 total tests in females, which is insane.
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Well, it might be worth talking about that for a second. I mean, we'll go back and talk more about
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TRT, but while we're on the topic, as you alluded to earlier, there is no FDA approval for testosterone
00:13:13.960
in the use of women. So there is for men, of course, and there's obviously an FDA approval
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for estrogen and progesterone in the use of women. The thinking with testosterone is that
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when a woman enters perimenopause, not only does she experience the predictable drop in estrogen
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and progesterone, but with it, so too goes testosterone. And of course, the rationale is
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that testosterone is still a very important hormone in women. I've pointed this out many times
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before, but the units that are used to represent estrogen and testosterone are very misleading
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because they're not the same. So if you convert them to the same units, you will see that even in
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a woman, her testosterone is significantly higher than her progesterone and estrogen. So if you took
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a mid follicular estrogen level, an estradiol level, and took it out of picograms per deciliter and put
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everything in nanograms per deciliter, her testosterone as a premenopausal woman would
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be at least 10 and at times even 50 times higher. So the idea is, well, clearly losing a hormone that's
00:14:20.400
that abundant must have ramifications. There are, you've alluded to all the side effects. And so the
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thinking is, well, we should replace it. And the question is to what? Now I've never heard a compelling
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case for why it should be replaced to a level that exceeds her physiologic limit in her thirties,
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for example. And I've never seen a woman in her thirties with a total testosterone between two and
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300 nanograms per deciliter. In other words, those levels exceed even her peak physiologic level.
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So it doesn't surprise me that that would be androgenizing women. Do you understand, or do you
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have a sense from the folks doing this, what their rationale is for going so high?
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I think their idea is simply that this is where we achieve blatant symptom relief in everyone and
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a feeling of optimization above and beyond. Like this is what it should feel like when you take
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hormone replacement. And I think it's just creating a state of ultimately androgens feel pretty good if
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you were just crashed or very low. And then all of a sudden you're essentially on the male proportional
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equivalent of like a bodybuilder cycle or something. So I couldn't say why they do it exactly, but all I
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know is it's too high and it's very, uh, common to have some of these like viralizing outcomes.
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And if you're not keeping a close eye on them, they can really, really snowball. Cause when you're
00:15:46.880
seeing yourself in the mirror every day and you're listening to yourself, you don't really notice these
00:15:51.180
little minute changes as much as somebody else. And then you might meet up with a friend a month
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later and they're like, what the hell? You don't even sound the same.
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Yeah. The other thing that amazes me is there's another symptom that is so common,
00:16:02.700
even at physiologic doses for women who are sensitive enough, because a lot of times you're
00:16:08.220
treating a woman and let's say she's 45 and she comes to you and she has almost unmeasurable levels
00:16:13.580
of testosterone. So she's sort of in the 10 to 20 nanogram per deciliter level. Now you didn't know
00:16:19.080
her when she was 30. So you don't actually know what she was when she was 30. People weren't measuring
00:16:23.200
her testosterone 15 years earlier. But you say, look, we're going to set a target of 80 to 100
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nanograms per deciliter, which is sort of in the ballpark of what would be kind of 70th to 80th
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percentile for women that age. But then it turns out that she probably was lower than that because
00:16:39.140
once you get her, her acne is out of control. You would surmise from that, that, well, she must have
00:16:44.880
lived at a lower level. And for her, 80 is super physiologic. And it's for that reason that I just
00:16:51.340
can't imagine that they're pushing women to 200 and 300 who are not developing horrible cystic acne
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and facial hair. Some of them like how much they feel so much. And now I'm having sex multiple times
00:17:03.840
a day, even with my husband who I didn't even want to touch a couple of months ago. So it's a pretty
00:17:09.280
big shift. And if they like what they're getting out of it, sometimes compromises will be made in order
00:17:15.420
to continue with what they think they need to be taking to achieve that feeling. And in addition to that,
00:17:21.080
too, like you said, with the not knowing where you were at further confounding, that is how many
00:17:26.200
people have been on combined oral contraceptives for like decades. Yeah. Just totally skews
00:17:31.080
everything. Yeah. Like I've dated girls who I've seen like 80% suppression of their hormone levels,
00:17:37.860
testosterone, free testosterone, especially proportionally more so to it because of the
00:17:41.460
rise. And the SHBG goes through the roof. Oh yeah, it's ruthless. So they're like operating in a state
00:17:47.260
of androgen deficiency perpetually and relying on this synthetic progestin to drive all testosterone
00:17:53.640
like behavior, essentially. And then if they get off, they don't even know what their natural
00:17:59.380
is like they've never experienced it because they've been prescribed it since 15 years old
00:18:03.340
or 16 years old or something. So it's tough because it's like you don't even know what your
00:18:07.380
ideal target is. Even if you were getting blood work, oftentimes it's totally skewed. And that's
00:18:12.780
something I definitely want to talk about on my podcast too is some of the testosterone
00:18:17.700
suppression in different formats of birth control because it's pretty nebulous some of it. Like
00:18:22.340
I'm very aware of the combined oral contraceptive data, but even like the localized progestins
00:18:27.540
and stuff, there's like very minimal literature shockingly. Like if I'm trying to find out how
00:18:32.800
much the Mirena affects my girlfriend, I don't even know. I don't know what her baseline probably
00:18:37.320
was. Have you been following at all the Netesto product?
00:18:41.220
Right. Looks good if you're willing to tolerate it.
00:18:44.000
Yeah. For folks who don't know, Netesto is an intranasal administration of testosterone.
00:18:49.640
And I believe the dose is like seven milligrams and it's used TID, so three times a day, which
00:18:55.940
tells you that obviously the bioavailability is quite low if you're taking 21 milligrams
00:19:00.780
daily. So that's slightly more than you would probably take if you were just doing it intramuscularly.
00:19:06.440
But nevertheless, the idea with it is it's quicker acting and that's why you have to take
00:19:12.060
it sort of three times a day because it's not sticking around like in a fat depot the
00:19:15.640
way an injectable source would be. But the interesting question is, does this help address
00:19:22.040
some of the female use case? So for example, if one of the symptoms that a female is turning
00:19:27.800
to testosterone for is libido, does she really need to be on mega doses of systemic testosterone
00:19:33.700
around the clock versus in the same way a man would use Cialis for an on-demand ED issue?
00:19:40.840
Could a woman be using intranasal testosterone for an on-demand libido issue?
00:19:46.940
I would hope that'd be the case. In practical application, I don't know if it plays out that
00:19:52.140
way where you could just acutely use it once a week or something on the day you're wanting
00:19:56.320
to get busy. I've candidly had some experimentation with it and it doesn't seem to make at least
00:20:06.060
No, with a female with like a low testosterone.
00:20:08.240
Because I was going to say in a male, I wouldn't expect it to have an effect.
00:20:11.880
Yeah, yeah, yeah. But you're saying in a female with low testosterone, taking a couple of shots
00:20:16.600
of netesto didn't in the subsequent hours have much of an impact on libido?
00:20:21.640
No, but that's obviously N of one. I haven't actually seen the data in literature myself.
00:20:30.780
I'm not aware, but I believe there is a clinical trial ongoing. I think it might be happening at
00:20:35.760
And one thing I can say is as much as it sounds great, typically women don't like using it that
00:20:44.700
Yeah, it's like dripping down the back of their throat. It's invasive in a way that's
00:20:48.980
not very clean. You just feel kind of gross. I feel like a drug addict almost. You're like
00:20:53.600
snorting some shit before you go have sex every time.
00:20:57.300
Obviously, the not having sex and not having a libido, probably a worse outcome for many of
00:21:03.260
them. So if it works in the short term on like a use by use basis, I'm sure it's individual
00:21:09.480
case dependent. And I'm sure you could double up the dose and maybe get more of a bang
00:21:14.680
for your buck effect. I'm just like skeptical that anyone's going to use it more for novelty
00:21:23.040
I've never actually seen the product. I don't know what the viscosity of it is. I don't know
00:21:28.040
what the user experience is like. Is it particularly viscous or is it kind of like a nasal spray
00:21:32.800
that you would use for an antihistamine or something?
00:21:35.140
The one I had experience with was a compounded replica of that. So maybe the Natesto formula
00:21:43.340
itself is actually more tolerable. So I probably should have prefaced with that. But the compounded
00:21:48.720
variant that I tried that was replicating that product was not that pleasant. And it was like
00:21:55.880
I would want to see what the real deal product was like. Let's talk for a moment about DHEA.
00:22:00.780
So that's the other thing that seems to be all the rave today. A lot of my female patients
00:22:06.020
are asking to be put on DHEA. And I'm not sure where this came from because DHEA has been around
00:22:12.920
forever. It's one of the few hormones that's available over the counter. That's a relatively
00:22:22.860
Not in Canada though. Don't bring it back to Canada or else you get it.
00:22:25.580
That's my point. So even across the border with our neighbors that we're otherwise pretty similar
00:22:34.560
Yeah. If you have that, you're doing something more illegal than having anabolic steroids.
00:22:41.260
Wow. I did not know it was Schedule 1. And yet here it is. Go on Amazon and you can fill your
00:22:49.520
No, it makes no sense until you understand there's a dirty political story as to why that's the case.
00:22:54.460
There's some really backwards compound selections though that are banned. Like for example,
00:22:58.460
you can buy ephedrine in GNC in Canada. It's like why? It's literally used to make meth.
00:23:04.700
And then here, it's a lot harder to get ephedrine. But then you can get yohimbine here,
00:23:10.000
which is a fat burner we'll talk about later. And in Canada, it's banned. Who's selecting what gets
00:23:16.440
So a lot of women for some reason have recently, like in the past few months, been sort of saying,
00:23:22.280
I want to be on DHEA. I want to be on DHEA. And they're somehow being led to believe this is the
00:23:27.040
elixir of life. I'm sort of trying to scratch my head and understand why they're saying that.
00:23:31.660
Presumably they're saying, if my DHEA levels are low, it could explain my low testosterone. And
00:23:36.980
this is a quote unquote, more natural way to increase my testosterone. I haven't seen any
00:23:41.280
compelling data that DHEA does much of anything. What did the data say? I haven't looked in a decade,
00:23:45.860
by the way. So a decade ago, when I was really beginning to get interested in hormone tinkering,
00:23:54.480
Yeah. If you look in males, you will find no utility. It has no effect on testosterone.
00:24:00.940
At best, you get a spike in estrogen and no testosterone seemingly through, you know,
00:24:07.520
And yet it's a USADA water banned drug. It's treated just as testosterone would be or
00:24:12.800
which is wild. But in females, it actually is useful and can increase testosterone to the degree
00:24:20.100
that if you had, and this is a pretty wild study that I haven't really seen anyone talk about.
00:24:25.520
I'm sure somebody has, but a few years ago I was looking into for the very reason of my girlfriend
00:24:31.260
at the time was shut down to nothingness on a combined oral contraceptive. And I'm like,
00:24:35.960
what can you do in this situation? And I found some papers that showed using DHEA supplementation
00:24:46.400
And a full restoration of total and free test levels while still using your combined oral
00:24:51.880
contraceptive. To me, that's pretty damn impressive for something that's not a cream you have to apply,
00:24:57.280
spray you have to put up your nose. And this thing reliably, depending on, because again,
00:25:02.460
combined oral contraceptives, there's many different variants you could get. So depending on the brand,
00:25:07.560
you might have a progestin that's more androgenic or one that's less. Ethanol estradiol is or isn't
00:25:14.280
included. That will all vary. But in general, in like the traditional most sold and prescribed
00:25:20.540
combined oral contraceptives, it was restoring total test levels to that of baseline while staying on
00:25:27.340
what is otherwise a brutally suppressive compound.
00:25:30.860
And give a sense of what the increase was from what to what was total T.
00:25:34.400
Oh, it was like going from your natural 60 down to like 15 back up to 60.
00:25:40.400
Okay. So 4X bump in total T. This was only in women on an OC?
00:25:46.920
Yeah. There's probably data on just not on anything, but I don't recall off the top of my head.
00:25:52.560
So why do you think women would be more sensitive to this?
00:25:55.980
Probably because a significant amount of their androgen synthesis derives from adrenal
00:26:02.060
hormone production as opposed to men. It's like if you castrate a guy, you can still
00:26:07.220
squeak out 30 to 40 nanograms per deciliter from his adrenals. Yeah. And in females,
00:26:13.160
it seems to be similar depending on the woman, you know, proportionally.
00:26:17.680
But 30 to 40 out of her adrenals could be three quarters of her total testosterone.
00:26:22.780
Exactly. So for men, it's like a drop in the bucket. But for girls, it's like maybe three quarters
00:26:28.240
of the bucket. I'm going to check that paper out. But that might be a nice thing to have in your
00:26:31.420
pocket if you live in the United States. One thing I can say, though, is DHEA in women who
00:26:36.500
have natural levels that look pretty good. Like, let's just say you're on hormone replacement as
00:26:42.520
is. And then you think you need DHEA for some subjective feeling of well-being. There's no real
00:26:47.460
biomarkers to reinforce that you're deficient. Your DHEA looks normal. Your testosterone looks okay.
00:26:55.200
And there's not really like a clear reason. You just kind of think you need it.
00:27:00.000
Almost certainly the risk to reward is a little bit worse because acne on DHEA is very common in
00:27:07.220
women to a degree where it's like the proportional upside you get out of it. You're not going to get
00:27:13.060
as much anabolic activity out of it relative to seemingly the androgenicity impact systemically,
00:27:20.360
or at least in skin from what I've seen. Remind me, we don't measure DHEA levels. We measure DHEA
00:27:27.100
sulfate levels, correct? Yeah. That's the only proxy in like traditional blood work metrics that
00:27:32.900
I'm aware of to test for it. Do you know why? I used to know why we couldn't measure DHEA directly
00:27:38.160
in blood. I think the majority of it is sulfated. So getting a direct measurement is not as indicative of,
00:27:46.680
I don't know. The total body pool or whatever. Yeah. I wish I had a good explanation,
00:27:51.520
but I just know that's the proxy. It's kind of like, why do we check IGF-1 for GH? It's probably
00:27:55.060
something similar. Okay. What about the role of progesterone? What do you think the role of
00:28:00.380
progesterone is in both men and women outside of reproduction? So putting reproduction aside,
00:28:05.980
one of the things that we're doing a lot more with our patients, we used to be pretty quick to
00:28:11.540
abandon progesterone systemically if women were having any mood symptoms associated with a full
00:28:17.860
dose of it. And we would just very quickly adopt a Mirena progesterone coated IUD to give the
00:28:22.940
endometrial counterbalance to the estradiol to prevent the hyperplasia and obviously reduce the
00:28:27.860
risk of endometrial cancer with unopposed estrogen. But we're really seeing a lot of
00:28:34.160
women in the middle ground who maybe can't tolerate a full 200 milligram dose of progesterone,
00:28:39.880
which would be kind of the full dose, but feel great at 50 to a hundred. And so in many ways,
00:28:45.500
what we're trying to do is just find every woman's dose and what's the amount that you can tolerate.
00:28:51.260
And if it's sufficient, great. If it's insufficient, we'll backstop it with a Mirena.
00:28:56.480
Why do you think that is? Why do you think progesterone is so important for women?
00:29:00.620
Outside of reproductive standard utility, I think that it's more like if you look at a
00:29:07.900
steroidogenesis cascade, which is like in layman's terms, I guess, if you took cholesterol and then
00:29:14.140
all of the different things it could turn into when you cleave it and through enzymatic pathways,
00:29:20.060
turn it into glucocorticoids or like downstream to adrenal steroids and downstream to testosterone and
00:29:28.160
DHT and estradiol and estrone and all that stuff like that is called steroidogenesis,
00:29:32.760
the synthesis of all these steroid hormones in your body. And some of you guys might've seen this
00:29:38.580
chart before, and I'm sure you've showed it on the podcast. It's like this big messy thing that
00:29:43.120
has like 7,000 different pathways and it looks overwhelming, but up near the top where you start
00:29:49.000
to have cortisol production, you have some of this stuff upstream for glucocorticoids, as well as
00:29:55.260
where pregnenolone branches from like to actual androgens and upward to like adrenal hormones.
00:30:03.280
At the top, you have this downstream cascade from progesterone that leads to an array of metabolite
00:30:11.140
hormones that are pro-anzeolytic, as in they will be like anti-anxiety, kind of balance out the
00:30:19.520
sympathetic drive that you might get from androgens and also help you get to sleep. So that's why
00:30:25.780
progesterone is so useful at night. And it's kind of why it's placed at that time for dosing as well.
00:30:31.460
Taking it orally also is like impactful on the way it's metabolized out to get some of these
00:30:36.800
proportional metabolites too. Because if you had it in a cream or an injection, not only maybe is it
00:30:42.120
harder to get the dose you want out of it, but the metabolite content that you get is totally
00:30:46.260
different when you have a first pass metabolism versus you skip it. So with progesterone in
00:30:51.300
particular, it produces an array of different things, including but not limited to one is called
00:30:56.200
allopregnenolone, which is seemingly implicated to some extent in post finasteride syndrome, but also
00:31:02.760
very much in postpartum depression. And they've even created a synthetic analog of it now that they
00:31:08.020
use to treat postpartum depression, which is interesting. But all of those different metabolites
00:31:13.140
cumulatively, if you are deficient in some amount of them, depending on the individual's biochemistry
00:31:20.880
and genetic predispositions could result in like a more anxious human than otherwise. So the dose
00:31:27.760
required to balance out the androgenic signaling relative to all this other stuff going on,
00:31:34.280
I would expect it would vary quite significantly female to female. And especially when you are
00:31:40.100
backfilling hormones from a shutdown state, it's not endogenously regulated the same way when you
00:31:47.400
have feedback mechanisms. So you're kind of just manually shooting stuff at your liver and hoping
00:31:51.660
it's going to spit out the right amount of stuff. And you can only really do that through some sort
00:31:56.680
of titration slash experimentation and what dosages seem to produce repeatable outcomes in the literature
00:32:03.960
we have available. So I would imagine a lot of women would have a dose that is far less to achieve
00:32:09.940
the outcome they want or much higher or perhaps don't respond at all because it's not what they
00:32:13.760
need. Depends. But I think that would be my educated guess. Is there a role for progesterone use by men?
00:32:22.240
Yeah. So I said this last time and you seem baffled and it definitely does not have an approved use in
00:32:29.040
men. There's no literature that points to it as this is something you should use in men or replace.
00:32:33.520
But I do believe and see it play out where it could be useful to balance out some of that
00:32:41.440
sympathetic drive and whatnot. You could look at blood work and kind of see, okay, in my like
00:32:46.900
minimal negligible amount, should I be pushing that to the top of the negligible amount that is my
00:32:51.880
threshold? What doses do you see people using here? The same doses, like 50 to 200. That high?
00:32:58.040
Yeah. And what are the side effects of that? So if you are not on exogenous hormones,
00:33:03.620
it does have negative feedback. So similarly to most people are very familiar with how estrogen
00:33:10.500
has negative feedback to the hypothalamus, pituitary, testicular axis, and testosterone
00:33:15.640
through androgen receptors. But what often goes overlooked is some of the other hormones like
00:33:21.540
progesterone. So progesterone isn't as potent of a negative feedback regulator that I've seen,
00:33:26.520
but it definitely is. And it seems to maybe even have anti-androgenic activity as well.
00:33:32.740
And if it does that through competitive inhibition, or like, I don't really know off the top of my head,
00:33:37.640
I don't recall how it does it, but it does seem to produce anti-androgen like effects.
00:33:43.500
And some of it may be mediated through the negative feedback. And some of it may be inhibited
00:33:48.920
through actual like transcriptional activity. But ultimately, it's something that will lower your ability to have
00:33:56.520
androgen like effects in the body to some extent. But if you're on TRT,
00:34:02.000
doesn't matter because you're already shut down. Correct. So what would be the benefits when you're
00:34:06.760
on TRT? What is it helping you balance out clinically? I think very common, we will see
00:34:14.400
disproportionately high free androgen levels in men, especially when you look at a lot of guys will
00:34:22.700
look at their total testosterone, their free testosterone, their SHBG. But what often goes
00:34:27.520
overlooked is SHBG binds DHT with, I believe it's a five times higher affinity than testosterone might be
00:34:35.440
10. I think it's five though, whatever it is, it's much higher. And that ratio of DHT to testosterone
00:34:42.400
to estrogen, that's freely circulating. Like you're regulating mechanism in the body,
00:34:47.420
the primary one, because SHBG is like, the main thing that determines how male you are,
00:34:53.040
essentially. Well, besides the actual production of the hormones, but DHT gets bound up with five
00:34:58.620
times higher affinity than test, which is like 20 times higher than estrogen. So if you have that
00:35:02.800
regulatory framework kind of like, driven down through either a dose of testosterone that is
00:35:09.800
higher than you need, or like a super infrequent dosing pattern that results in like a disproportionate
00:35:17.040
drop on certain days or an array of different things, you could end up in this free androgen
00:35:22.840
dominant environment where your sympathetic drive is kind of like keyed up perpetually. And because
00:35:27.800
you have a long ester compound in your system, you don't have the luxury of endogenous manipulation
00:35:34.400
of your hormones going up when you need them and down when you need them, like the pulsatile
00:35:38.840
framework of your natural production is non-existent. You're just like getting a big spike whenever you
00:35:44.580
inject. And then it's slowly going to diminish out of your system until you want to inject again.
00:35:48.520
And a lot of guys, even when they're doing, you know, twice a week or something, you're still
00:35:52.700
getting like some level of spike and then dips and then spike and dips, where if you were a natural
00:35:58.880
with normal natural testosterone production, it would be like very pulsatile with a diurnal rhythm with
00:36:04.860
natural dips and valleys and peaks. And it would not fluctuate where it's like, bam,
00:36:10.600
bam. And if you look at a steroid plotter, you can kind of see how this looks. And you want to
00:36:14.900
compare a steroid plotter to your actual rhythm naturally. It's like not really the same. So
00:36:21.380
that's kind of where you get into, you know, more frequent dosing might be better. But at the end of
00:36:26.320
the day, a lot of people are overlooking how dominant the free androgen profile could be in a
00:36:32.500
guy on TRT because you'll see your total testosterone and it might be 700 when you measure it,
00:36:38.000
but you're measuring it three days after your injection. You're looking only at free testosterone.
00:36:44.000
Your DHT has not been evaluated. Your free DHT surely hasn't been evaluated. I don't necessarily
00:36:49.080
think everyone has to spend hundreds of dollars to check those by the way, but just be aware that
00:36:53.040
if your SHBG is lower than it was before you started TRT, there is a disproportionate regulating
00:37:00.500
mechanism in play here now that you have to perhaps account for if you're in like a state of anxiety,
00:37:06.260
that might be a factor. Or if you have trouble getting to sleep, there are certain cues I would
00:37:10.620
look to as to, am I a little bit too redlined right now? Given that free testosterone is typically
00:37:17.480
estimated, I guess we can talk a little bit about testosterone measurements. You were mentioning
00:37:20.840
earlier that there's a direct way to measure free testosterone. I was unaware of that. Do you
00:37:25.260
look at free androgen index where you're just taking the ratio of testosterone to SHBG? So you're
00:37:30.780
taking the ratio of two things that are directly measured. Is that a better proxy for what's
00:37:35.640
happening physiologically than this indirect calculation of free testosterone? Which,
00:37:42.160
I mean, again, if my memory serves me correctly, free testosterone is a calculation based on
00:37:47.960
testosterone, SHBG, and albumin. Is there anything else that factors into it?
00:37:53.200
Yeah, I'm pretty sure the free direct measurement via LabCorp is just based on those binding proteins.
00:37:58.860
I don't think there's anything more to it. But with the equilibrium dialysis, it is separating it
00:38:04.640
and measuring it directly. And does LabCorp do an equilibrium dialysis?
00:38:09.660
Yeah, it's just more cost prohibitive. So the good news is a lot of these tests,
00:38:15.600
when they evaluate them against it as a gold standard, track pretty closely with it. So you
00:38:20.300
can use them as proxies that are relatively accurate. It does get skewed when you get into
00:38:25.720
trying to measure hypogonadal men that might have, you need to be a bit more, I don't know,
00:38:31.340
lower concentrations, and you want to make sure you get it right. It's not just tracking trends
00:38:35.780
as much. Or individuals who are using synthetic androgens, it will for sure cross detect if you're
00:38:42.060
using a immunoassay or a calculation, because it's going to be based on the cross detection of the
00:38:47.640
total testosterone, presumably as well, if you use that. So in general, if you wanted to use the gold
00:38:53.760
standard, it would be equilibrium dialysis. I don't know if it's always necessary. However,
00:38:59.120
at baseline measurement for people who are trying to get as ideal and accurate of blood work as
00:39:06.000
possible, I would typically always go with the highest sensitivity. And that's even with your
00:39:10.360
blood work, it's not like it was wildly different on some of the metrics, but like it was significant
00:39:15.020
enough. Yeah, let's talk about that. So I wrote my values down. So for my last blood test, I did it.
00:39:20.880
I had LabCorp run them both. I had them run the immunoassay, which is not the gold standard. That's the
00:39:27.280
cheaper test for both testosterone and estradiol, and then the LCMS, which is the gold standard.
00:39:34.260
And so here's the difference. So the enzyme-based immunoassay for testosterone was 502, but the LCMS
00:39:42.180
was 381. So for people who want to know how to tell if the test is that one, it says Roche, E-C-L-I-A,
00:39:51.500
right beside it. Yeah, so Roche is the company that provides the assay for them.
00:39:55.420
But that's like the only thing I think it says underneath it to identify.
00:39:59.100
Yeah. Yeah. So that's a pretty big difference, right? I mean, that's a 25% difference.
00:40:04.380
I think it's significant enough to justify getting the accurate one.
00:40:08.240
Yeah. And that's the only one we do, but I just wanted to see what the difference was. So the
00:40:12.840
accurate test read 381 to the inaccurate 502. Here's what's more telling was the estradiol.
00:40:19.540
So the estradiol on the accurate test, the LCMS was 18.3. And on the enzyme-based test,
00:40:28.380
it was 41.3. So that's more than a 2x difference. Yeah. The enzyme-based testing will cross-detect
00:40:35.220
estrone synthetic estrogens as estradiol, and it's annoying. I mean, that still seems really high,
00:40:43.260
right? Given that my estrone, my estriol, they should be very low. I'm obviously not taking any
00:40:48.820
synthetic estrogens. Why do you think it's off by more than 2x? And by the way, I see this
00:40:54.080
in other patients as well. That would be tough for me to speculate without seeing the full
00:40:59.640
gamut. I think it's picking up something in my supplements. Like I think there's something else
00:41:05.020
that's being detected. Now that you say that, probably. Yeah. I'm assuming you didn't take
00:41:08.820
any biotin for- Ever taken biotin, yeah. Okay. You don't have any methylated B vitamins, bro?
00:41:14.580
I do have methylated B vitamins. But biotin's not in your B complex?
00:41:17.440
I don't think it is. Maybe it is in tiny amounts. I'm not taking a dedicated biotin,
00:41:22.520
put it that way. That would still mess with it. Yeah, maybe. So maybe there's something in my
00:41:27.200
methylated B complex. Stuff you should not take before your test. Last time we spoke,
00:41:33.140
you said, we were both aware of biotin. And then you said, I'm not sure if there's other stuff that
00:41:37.620
could affect it. I checked with Merrick Health, which is my team, and they don't know of anything
00:41:43.260
either. So I think biotin is the main thing. And I think it skews, if I recall correctly,
00:41:47.600
thyroid values pretty dramatically as well. So if you're taking a biotin supplement,
00:41:52.980
it's worth noting you should stop it periodically before you take a blood test for, I would say,
00:41:58.080
at least a few days, if not a week, probably before your test, just in case.
00:42:02.580
Okay. So let's now shift over to the testosterone replacement decision-making in a male. So it seems
00:42:10.500
to me that younger and younger men are seeking out testosterone replacement therapy. Is there any
00:42:16.020
data on that? Or is that just sort of our perception? No, you're right. As far as marketing
00:42:21.080
efforts and exposure, if you look at just Google Trends and you type in TRT, it's like the graph of
00:42:26.420
how many searches are on Google is skyrocketed over the past decade.
00:42:29.980
Where do most men get their TRT? How much of it is done from an endocrinologist, for example,
00:42:37.580
like someone who presumably spent a lot of time understanding the system? How much of it is done
00:42:43.180
from clinics that only do testosterone as the other extreme example?
00:42:49.100
Yeah, it's tough because countries will differ in their scrutiny on this stuff to such a varying
00:42:55.080
degree that if I speak, I could speak to the US and give some sort of ballpark. And I feel that's
00:42:59.960
probably the most useful. And again, this is not based on some sort of survey or anything. This
00:43:04.800
is just my speculation as to what I would imagine is happening from trends I've seen. Underground
00:43:11.020
market is still the most easily accessible with the cheapest barrier to entry. And with the advent of
00:43:20.040
internet e-commerce stores, it's not that difficult to find a website that sells testosterone or
00:43:27.360
other anabolics and get some Bitcoin and buy it. So there's a lot of people that will
00:43:32.080
get it from their gym bros or online. It's very accessible. Now the cost aside from the prescription
00:43:39.820
barriers of finding a doctor who you actually think will give you the prescription and not necessarily
00:43:46.880
knowing when you go into that consultation or whatever, that they're going to be, you know,
00:43:50.200
the flexible doctor that you need. It's just easier for a lot of guys to get it black market.
00:43:54.880
So there's a significant amount of guys, at least in the fitness industry that are suppressed from
00:44:00.560
their hormone use that will be on TRT underground. So I would say there's probably the majority of them
00:44:06.220
are on not scripted TRT, even like lenient telemed clinics. I would say a majority are still using
00:44:12.880
underground. Presumably crypto is what enables that because otherwise the DEA would shut these things
00:44:18.180
down. Or is it too much of a game of whack-a-mole or there's too many of these around?
00:44:21.260
Whack-a-mole. Yeah. So there's a lot that sell an amount of volume, presumably that is not
00:44:27.920
significant enough to focus on, or it's just like, it's so hard to track because even if you shut one
00:44:34.120
down, another one pops up, it's based in some country that's not even the US supposedly. And
00:44:39.620
they drop ship it and they use crypto. So it's harder to attract the currency.
00:44:44.220
Got it. And what kind of testosterone are these guys getting? Are they actually getting branded
00:44:48.360
depot testosterone? Are they getting some knockoff from China?
00:44:52.260
Often it's underground, but there are resellers of pharmaceutical grade too. And sometimes these
00:44:57.380
guys will have connections with people in Europe, in certain countries where you can just walk into
00:45:02.560
a pharmacy and buy whatever you want for one 10th of the price. And then they will mark it up and then
00:45:09.700
sell it to you in the US. And yeah, so there's an array of different options, but typically it is a
00:45:15.740
underground lab that is producing it and making what they're advertising as a accurately dosed
00:45:21.980
sterile product that is branded under their like underground lab brand, essentially.
00:45:27.340
Okay. So for folks that want to do this in a little bit more of a responsible way and go and
00:45:32.180
see a doctor, there are a lot of these doc in the box operations where they're basically just
00:45:37.660
T docs. I don't know how they're operating. I assume that a lot of this is telemedicine.
00:45:43.760
And I don't know how much longer that will be in existence. I do believe that a lot of that stuff's
00:45:48.900
going to be shut down. But for the time being, you want to just talk maybe a little bit, I know we
00:45:53.980
talked a bit about this, but anything else you want to say on the Clomid, Eclomid, HCG, T trade-offs?
00:46:02.680
I think when you are trying to restore fertility in the short term and you're averse to injections
00:46:10.040
and there's a lot of factors that could lead me to say Clomid might be viable. But in general,
00:46:16.100
if you're looking at something long-term, I would say typically Clomid or N-clomiphene, which is a
00:46:23.140
more progressive version of the drug, all but not FDA approved. Neither of those I think are viable
00:46:29.380
long-term, at least from a risk perspective. You are essentially putting yourself in a position of
00:46:35.880
long-term estrogen receptor antagonism in certain tissues, meaning you're going to be missing out
00:46:41.960
on estrogen receptor activity in certain areas of your body that down the line could manifest an
00:46:49.040
array of issues. Like if you look at the side effects of CIRMs, you'll see weird stuff depending
00:46:54.000
on the compound. Sometimes it's ocular issues. What do we know about the long-term use of Clomid?
00:46:59.720
We've got more data for Clomid than we do N-clomiphene, which is, as you said, just a very,
00:47:04.980
very close derivative of it. But they both work the same way. They both block the estradiol receptor
00:47:10.360
of the hypothalamus, correct? Yeah. And then the zoo-clomiphene component of Clomid has two drugs
00:47:17.820
essentially in it because they will have differing effects. That component of it is more
00:47:23.960
anti-gonadotropic, I believe. So it's like the N-clomiphene component is far more specific to
00:47:29.940
the CIRM activity you are seeking in the hypothalamus. The zoo-clomiphene is longer
00:47:33.800
half-life, less efficacious, doesn't even really represent the target therapy of the drug. So
00:47:38.980
in general, if you're looking at Clomid, that's the only one that has approval. So you would
00:47:43.320
potentially have the data. But I, off the top of my head, don't know of any studies that are going
00:47:48.460
decades long to evaluate something like that. I don't know if it exists. I would be kind of doubtful
00:47:53.400
it exists, to be honest. But I would think from what I've seen, at least anecdotally,
00:47:58.740
take from that what you will, is typically no one ends up with a stable mood long-term.
00:48:06.160
It's not a sustainable therapy long-term, in my opinion, for the vitality component you seek
00:48:11.440
from replacement therapy to begin with. So perhaps on paper, your testosterone looks good,
00:48:16.460
but it's more of a metric that you're using to justify the drug because you are achieving
00:48:23.260
the target, which is, look, my testosterone is better now, but at the expense of literally
00:48:29.640
tricking your brain through inhibiting very, very necessary mechanisms. So it's not like you are
00:48:36.280
stimulating production through a means that is directly targeted. It is more like you are trading
00:48:42.540
off the health of one part of your body to get an outcome that is potentially ROI justifying in
00:48:50.060
another aspect of your body. So at the expense of estrogen receptors working everywhere in the body,
00:48:54.320
you're getting more testosterone. And is it blocking estrogen receptors everywhere or just
00:48:58.380
centrally? Yeah, it is selective, hence CIRM, but it's not perfect. As we talked about last time,
00:49:04.960
you were going to get, we could just Google Clomid side effects and you'll see an array of different
00:49:09.200
things, I believe, including but not limited to skewing of lipid parameters. You were the one who taught
00:49:14.320
me about, you know, it's a cholesterol. Yeah, like that's sketchy. I wouldn't want to have that long
00:49:19.300
term. Like there's stuff you'd have to track that are very unknown variables. At least we kind of know
00:49:24.280
what to expect when you have natural testosterone increasing what happens at a lipid perspective or a
00:49:30.820
negative feedback perspective, or you're not dealing with some, I don't know, nebulous activity in
00:49:37.220
different tissues and having to account for it. So actual brain inhibition is sketchy to me.
00:49:43.660
And from what I've seen, people end up not in a good state of mind long term on it. I suppose
00:49:49.220
it's possible you could. What doses are you seeing people use in the wild? 50 milligrams daily,
00:49:55.400
50 milligrams three times a week? Around 50. Obviously in the bodybuilding world,
00:49:59.680
I told you about the absurd PCT regimens, post-cycle therapy where guys are using 100
00:50:03.620
per day for shorter timeframes, but it's super high doses. I think we're going to see a big increase
00:50:12.080
in the use of Clomid and E-Clomid even beyond what we're seeing now, just based on the regulatory
00:50:17.220
environment, which is to say that there will be no use of telemedicine for the prescription of any
00:50:24.940
scheduled compounds. So that means that testosterone and HCG, which we'll talk about again in a second,
00:50:31.120
can only be prescribed in person, at least if you're adhering to the law. Whereas via telemedicine,
00:50:37.000
you could still use Clomid or potentially E-Clomid. So that just sort of suggests that
00:50:43.680
we're going to see HCG kind of plummet and Clomid go up. So I think the implications of
00:50:50.000
understanding this are actually pretty significant and I'd really like to see this studied better
00:50:53.660
because everything about Clomid is easier to use. You're going to have this, you're going to get over
00:50:58.200
the regulatory issue. It's oral, it's a pill, you don't have to inject it. HCG, as we've talked
00:51:03.420
about, is a bit more difficult to use because it needs to be refrigerated. It's a very fragile
00:51:08.380
peptide and it's probably more expensive than both testosterone and Clomid put together, right?
00:51:13.140
Oh yeah, for sure. Anything you want to just say about HCG that we didn't cover last time?
00:51:17.300
I think that if you were looking to restore natural production or assess your testicular response in
00:51:26.060
general before you decide to go down the TRT pathway could be a worthwhile thing to do. So if you're
00:51:32.580
considering TRT, you have a total testosterone of 300 or in your symptomatic, 381. Yeah. And let's
00:51:39.960
just say you're symptomatic. Don't even remember the last time you had morning wood. Your energy
00:51:44.220
levels are much lower. It's much more difficult to retain muscle, et cetera, et cetera. Actually
00:51:49.780
looking at your blood work to assess what is the release from my pituitary down to my gonads to
00:51:57.240
actually produce the testosterone. What is that signal? And is it sufficient? So do I have in range,
00:52:04.620
high normal? Like what does it look like on my blood work of my luteinizing hormone, LH and FSH?
00:52:10.560
And if it looks to be adequate or even high would be even more indicating if something's wrong,
00:52:18.160
you could determine from there, why are my testes not responding to it?
00:52:22.140
I mean, Clomid gives you two pieces of information, right? It tells you the pituitary
00:52:26.640
response and the gonadal response. HCG will only give you the gonadal response. You're not
00:52:31.200
getting any pituitary information out of it other than the shutdown, but that's not real. That's
00:52:35.520
obvious. Correct. But I was just saying, as far as interpreting the blood work to understand what
00:52:39.780
luteinizing hormone even does in general, you would be looking to your response at the testes
00:52:45.460
to this signal from your brain. And if you're going to use an HCG, you can mimic that, which is
00:52:50.760
HCG essentially, it's not identical, but it looks very similar to LH and it behaves in a very similar
00:52:58.400
way on the luteinizing hormone chorionic gonadotropin receptor, which initiates the light
00:53:06.400
excel stimulation and intratesticular testosterone production that you would want to actually produce
00:53:12.960
natural testosterone. And when you use an HCG, it's the only way you can directly do that if you
00:53:18.440
had an inadequate signal. But the only viable way that would be something you could stick to
00:53:24.520
and have as a monotherapy, as in it's the only thing you're using for your HRT,
00:53:29.800
is if your testes are healthy enough to respond to it to make the testosterone. So when people are
00:53:36.220
trying to determine if they should take literal synthetic testosterone, I feel it's worth fleshing out
00:53:40.700
what is my actual health of my testes first. But let's say you learn this. Okay. So let's say
00:53:46.760
with my testosterone of 381, I take HCG and my testosterone goes to 1200, 1000, 1200, like it
00:53:55.440
goes to upper end of the range. So we've learned that, Hey, my hypogonadism is central. It's not
00:54:04.080
peripheral. Somehow my pituitary isn't making enough signal because clearly my testes can make
00:54:10.760
enough testosterone. Armed with that information, what is the best course of action? Is it to stay
00:54:16.900
the course and just say, well, Hey, keep taking HCG because at least your testes are responding to it
00:54:23.420
or there's some obvious problem solving. And I'm thinking about this even in my case, right? Because
00:54:28.280
when I think of all the things that would normally impair pituitary function, the first thing that
00:54:34.320
comes to my mind is sleep disruption, knock on wood. That's one thing I've pretty much got down in
00:54:39.020
the toolkit. My sleep is great. Maybe stress, probably hypercortisolemia, maybe not so great
00:54:45.100
training, overtraining, undertraining. Like what are the things you would look at to brainstorm if
00:54:49.820
that scenario were the case? I don't know if that's the case by the way, but that's an experiment
00:54:52.820
that probably worth doing to see, Hey, why is my T low? Is it low because my brain isn't saying the
00:54:59.680
right thing or is it low because my body can't do it? Yeah. I think there is multiple factors here
00:55:05.400
that could be fleshed out before you ended up on an HCG to even figure out, you know, what's my
00:55:10.780
response at the testes level, figuring out if you can top out the natural signal I feel is the first
00:55:16.060
thing to do pending your blood work looks like gonadotropins are low to mid range. Why am I only
00:55:24.880
getting a 381 response out of that? It would be to look to many of the things you just said,
00:55:29.960
which obviously you're pretty dialed on. And then above and beyond that, it would be assessing
00:55:34.320
the basics like micronutrient intake macros. Are you eating enough to recover relative to your
00:55:39.840
training stimulus? I'm not going to say a lot of people overtrain too much. Maybe they're just
00:55:44.040
under recovering and their sleep is bad. That's probably a more realistic outcome. But in general,
00:55:49.120
there is not in your case, but in many other individuals, micronutrient deficiencies across
00:55:54.500
the board, zinc intakes not being adequate amounts, magnesium intakes super low, and that's
00:55:59.520
impactful as well. An array of things, vitamin D being low, also very impactful. And these things
00:56:04.580
can all move the needle like a hundred plus nanograms per deciliter, potentially depending how
00:56:08.500
deficient you are. So some of these low hanging fruits with the sleep, micronutrients, minerals,
00:56:14.040
actual macro intake, some people are eating ultra garbage processed foods,
00:56:19.200
no micronutrient density, they're under eating, maybe they're on semaglutide and they're super
00:56:23.960
calorie deprived and they have very low protein or something. That's also impactful. All of these
00:56:29.220
assessments, do I have an adequate energy intake? And of that energy intake, high quality nutrient
00:56:35.440
value in that energy relative to my demands? Am I training hard enough to actually maximize the
00:56:43.340
testosterone too? Because that's also a factor is your resistance training regimen and the sleep,
00:56:47.620
all of these things in concordance will ultimately dictate what is your output. And then let's just
00:56:53.040
say you've had that all dialed in at that point, if it's still either suboptimal signaling, so low
00:57:00.740
normal, whatever it is, or even normal, gonadotropin output, and then you're still getting an inadequate
00:57:05.520
response, you could then potentially discern partly that you're not going to be able to get the signal
00:57:11.340
you need out of your pituitary to optimize, or you actually have some degradation of response at the
00:57:16.780
receptor level in the testes themselves, which is an age deteriorated thing as well. Unfortunately,
00:57:22.040
like I would love to just say everyone's testes are going to retain perfect function forever,
00:57:26.680
but it's not the case. So similar to the signal, there's also the health of the actual organ. So
00:57:31.280
if those things are all optimized, you've kind of done your due diligence. It's just making sure you
00:57:35.540
actually know what the due diligence is. And if those things are optimized and you're at 381
00:57:41.360
and you take HCG and your T goes up, what does that imply? That there's some other factor that
00:57:48.740
we're unaware of that's impairing central stimulus? Yeah, I would be like, what's your GNRH output then?
00:57:53.900
Not that I know how you could even measure that, but presumably that may be low or the receptor
00:57:58.680
response to the GNRH is suboptimal too. Yeah. Interesting. So it's like a whole upstream.
00:58:04.020
Yeah. That's interesting. That's the problem with these. Is there anything that you could use a
00:58:08.400
GNRH agonist and even test out what your pituitary output is from there, but that's like good luck
00:58:13.660
finding a doctor who understands the nuance of not castrating you with that. Yeah. Although what you
00:58:18.700
could do is then you could use Clomid. Sure. Right. So then you could say, okay, if the response to HCG
00:58:24.080
is favorable, then you know, directly stimulating the late egg cell produces testosterone. Assuming you had
00:58:30.260
enough testosterone to aromatize to estradiol, that was a meaningful impact from inhibiting its
00:58:35.540
negative feedback to begin with. At least with a GNRH agonist, I know I'm maximally stimulating
00:58:40.780
pituitary output to whatever capacity it is. With Clomid, I'm just inhibiting negative feedback to
00:58:46.460
whatever suboptimal capacity my ER is agonized. Yep. Although you'd want to think if you gave a high
00:58:52.780
enough dose, yeah, you're right. In my case, maybe that wouldn't work because my estradiol is so low to
00:58:57.740
begin with. You're not inhibiting that much. That's a very interesting point. If estradiol is
00:59:01.840
really low, Clomid could fail just on the basis of that. Like if you really wanted to test pituitary
00:59:06.920
output potential, you would use a GNRH agonist and see what happens. Is there one out there?
00:59:13.800
Ganadorelin is often used and I think misrepresented as a HRT therapy. It is a GNRH agonist. There's other
00:59:21.540
ones that are used for other indications, but like, yeah, they exist. It's interesting in that the
00:59:27.020
question is that what's the so what, right? Like, so this is a super interesting line of inquiry and
00:59:32.640
let's say you learned, oh, you respond favorably to HCG. You do not respond to the GNRH. Oh, well,
00:59:40.920
then the problem is something is wrong at the pituitary. The pituitary is missing the signal.
00:59:46.120
I've seen people diagnose adenomas by actually digging into that stuff. So I think it's worthwhile
00:59:50.620
to understand because maybe you have, again, it depends how long you've been monitoring your
00:59:56.520
hormones. Like, have you always been a healthy person? Well, this is where maybe the endocrinologist
01:00:00.420
can really do the heavy lifting here, right? Like if you go and see a physician who day and night is
01:00:06.980
thinking through all of the intricate pathways here, yeah, maybe there is a micro adenoma. I mean,
01:00:12.660
one of the things we like to do in people when we can't solve this problem before we send them to
01:00:16.280
an endocrinologist is measure prolactin, ACTH, a few of the other pituitary hormones to kind of get
01:00:22.380
a sense if anything else is out of whack. Yeah. Sometimes you'll have like a prolactin
01:00:26.820
secreting adenoma too, and it's problematic as well. There's a lot of weird stuff that I would
01:00:32.260
love to say you should understand this before you take hormones for the rest of your life, but it's
01:00:37.120
hard to expect everyone to understand this access to the degree where even we're going back and forth.
01:00:42.360
Like, what about this? You just have to find as good of a medical provider as possible, I suppose.
01:00:49.060
Yeah. I mean, I do hope that people take from this discussion the following, right? Which is
01:00:53.300
HRT is serious business. I do think a lot of people are doing it incorrectly, and I think there are a
01:00:58.880
lot of really irresponsible people out there who are frankly just practicing dangerous medicine,
01:01:03.840
if not veterinary medicine outright. And again, I don't see a lot of this in my practice.
01:01:09.080
There are usually people aren't coming to see me who have been terribly decimated by someone doing
01:01:15.100
awful HRT in them, but I can see people on YouTube where I'm shaking my head going,
01:01:20.300
oh my God, what's that guy talking about? What's that guy doing? So there is clearly a use case to
01:01:25.960
understand this stuff before you go down the rabbit hole, and hopefully this type of content helps.
01:01:30.300
Anything else you want to say on TRT before we kind of pivot to something else?
01:01:33.720
Yeah. I guess just to put a bow tie on the whole natural stimulation thing, I do think if you are
01:01:41.500
mindful of fertility, it's worth consideration of HCG concurrently with whatever you're going to be
01:01:48.820
using. If you're on TRT and you're going to shut yourself down, don't make the mistake that
01:01:53.700
thousands of bodybuilders have where they got on hormones, ended up with atrophy testicles,
01:01:58.500
and then when they were 10 years later, wanting to have a child, realized the arduous recovery
01:02:03.780
process was like pretty significant. Are there guys that can recover after 10 years of TRT?
01:02:10.180
So I dug into that because you asked me about a five-year last time I was here. The longest I
01:02:14.420
could find was four, and it seemed to be pretty reliably restored, but there are some that just
01:02:22.880
doesn't seemingly. So you're saying someone is on uninterrupted testosterone replacement therapy,
01:02:28.500
for four years. These were abusers. Okay. So they're on very high doses.
01:02:32.620
But it's not like a controlled trial too, where it's like, you're going to take
01:02:35.920
super physiologic TREN. It was like, you guys abuse some amounts of synthetic drugs and have
01:02:40.840
been shut down. And to rescue these guys, they were using recombinant FSH and HCG in megadoses?
01:02:48.160
No, they were just doing whatever PCT they deemed worthwhile in general. Some of them, no PCT.
01:02:53.980
Wasn't it a trial where they all got a fixed- Oh, I see. It wasn't a standardized recovery.
01:02:57.920
Yeah. But what I've seen, at least from these studies, which admittedly, it's not like I'm
01:03:04.620
behind them or anything, so it doesn't really matter, but they're not the most high-quality
01:03:08.080
controlled things, but it's very difficult to control for illegally used drugs at abusive
01:03:14.020
dosages in random bodybuilding population. So what we see though in general is once the hormones have
01:03:20.700
left your system and there's no more residual negative feedback, there is a recovery period that
01:03:27.480
could be as short as weeks to months, but in general, most people will recover within one
01:03:34.380
to two years, even if abusing. Yeah. But it's not 100%.
01:03:39.960
Okay. When we last spoke, we talked about a whole bunch of peptides.
01:03:44.740
Just recently, meaning after we spoke, but before this discussion, the FDA came out and took a list
01:03:54.360
of about 30 peptides and put them on a list called category two. Now this included six of the peptides
01:04:00.180
we discussed, including BPC-157 and what is it? CJC-1295, ipamaryllin.
01:04:08.100
That's right. So a bunch of the things we talked about are now on this category two list,
01:04:12.140
and I've been doing my best to understand what that means. My interpretation of what it means to
01:04:16.680
be category two is these can't be sold. Compounding pharmacies cannot make them. And any interstate
01:04:24.160
commerce of these things is a felony. That said, I've noticed that there are still sites selling
01:04:30.840
these peptides and they seem to be suggesting that they're selling them for research purposes,
01:04:36.780
which is clearly bullshit. What's your understanding of this FDA ruling?
01:04:41.320
I think that the ruling has basically put them on a super high risk list, essentially,
01:04:49.320
whereby they're not outright banned, but you will invite heavy scrutiny and perhaps legal action
01:04:55.660
should you decide to make them. Maybe it's not comparable, but in the dietary supplement world,
01:05:01.620
they have an advisory list and they will pick certain things they think are high risk
01:05:06.100
and add them to this list. And then if you continue to make or sell these, you may receive a warning
01:05:12.400
letter, at which point you have to either discontinue immediately or they will take you to court and you
01:05:17.040
have to prove why it's DeShia compliant and legal to sell. And you could have a court appearance where
01:05:23.580
you could try and make your case, but you will lose essentially. So I don't know if this is going to be
01:05:28.960
the exact same outcome because it's pharma stuff too. So it's probably heavier scrutiny,
01:05:33.360
but from the people I've talked to in the compounding world, people who even are in the
01:05:39.960
business of selling peptides, they seem to think the commonality that I'm seeing is it is very risky.
01:05:48.480
It was already risky to begin with, but it's very risky and you are inviting scrutiny, but it's not
01:05:54.060
necessarily actually illegal. They could easily prove it probably if they wanted to and took you
01:06:01.240
to court. But I don't know that all of them are going to get whack-a-mold. I feel like it might be
01:06:06.240
a scenario like that. And when you look at these research chemical sites, they are no different
01:06:11.000
than they were months ago. Like these are the same sites that have been operating with their pseudo
01:06:14.960
research chemical use only fake umbrella the whole time. Those companies exist to try and sell
01:06:22.660
whatever with no prescription, no compounding pharmaceutical standards. Like at least in
01:06:28.820
compounding, there is some level of oversight where you have to be plus minus some amount of potency.
01:06:34.380
You should be submitting it for microbial testing and stuff. And in this world, it's buy it from
01:06:39.220
Alibaba, private label it, and then you sell it online. That's what these research chemical sites are.
01:06:44.060
So maybe some of them are doing HPLC testing, but that's like the really responsible ones. If you want to
01:06:49.720
call it that, relative to the rest of them that are just straight up buying it, repackaging it,
01:06:53.660
and selling it. Do people buy there with a credit card or they're not having to use crypto to buy
01:06:58.380
through these sites, are they? I think it depends on how big the company is because sometimes you
01:07:04.580
could get away with credit card processing up to a certain amount until Stripe or whatever your
01:07:10.720
processor is determines you're doing something high risk that's not a part of their compliant
01:07:15.280
activities. And up until that point, oftentimes they're accepting credit cards. So the bigger
01:07:21.000
companies will do Bitcoin only or other more loophole ways of paying, MoneyGram, Western Union,
01:07:28.280
stuff like that, typically crypto. Yeah, some companies do credit card too.
01:07:33.360
So the rationale for putting these 30 peptides on this category two list provided by the FDI is it's a
01:07:40.860
safety question. So the question was, we don't have sufficient data on the safety of these things.
01:07:46.140
So we're going to sort of schedule them in a way. Was there anything else to it? I mean, is there any
01:07:50.300
reason to believe that these things were harmful? I guess I just don't really understand what the
01:07:54.680
rationale was. And by the way, I'm not saying I necessarily disagree with it. I just, I'm trying
01:07:58.780
to understand what's being communicated in this ruling with respect to these peptides.
01:08:03.880
I think publicly what they're saying is it's a safety concern,
01:08:06.720
and there's no actual FDA approval to justify the production of these and prescription of them,
01:08:14.020
which is not the most unreasonable conclusion, I suppose, given that a lot of these are research
01:08:20.740
chemicals at the end of the day. Like it's not like melanotan too has a application right now for
01:08:25.820
somebody who's too white. So some of this stuff is very fudged at the end of the day anyways,
01:08:31.860
with compounds that got abandoned in the middle of a pipeline, but people had a demand for it. So
01:08:38.360
the research chemical companies have never stopped selling it. And then compounding pharmacies,
01:08:43.020
the ones that are willing to risk it for the biscuit will, you know, make a certain amount
01:08:47.700
in quantities that they deem is enough to satisfy the perceived demand, but not enough to get whack-a-mol
01:08:53.340
potentially. So it's really weird because you would think it'd be black and white. You don't make it
01:08:57.940
or you make it illegally. And that's kind of it. I think a lot of people do believe that it's
01:09:03.020
gray area enough that it is still legal to make. And there are small compounding pharmacies that are
01:09:08.340
going to do business as usual. I think some of them are looking to other abandoned pipeline products
01:09:14.740
now to replace the existing ones because those aren't on the list, even though they're similar
01:09:18.880
mechanism of action or whatnot. And you could find a catalog of Frankenstein compounds that a pharma
01:09:24.500
company didn't want and get it from China and then do the whole process over again. Cause
01:09:29.920
there's endless amounts of those. Why do you think there's such an epidemic of interest in this stuff?
01:09:36.220
I'm constantly amazed at the frequency with which people forward me links to these bizarre molecules
01:09:45.620
that they've heard some influencer talking about on social media. And they're asking me,
01:09:51.800
should they be on it? My patience for it is so low. It's so thin when it's like, if you would spend,
01:09:59.160
I don't know, take half the amount of time you scroll social media looking for obscure molecules that
01:10:06.880
idiotic influencers think you should be taking and maybe put it into working out. Call me then.
01:10:12.720
Is this just a symptom of our quick fix obsession?
01:10:15.940
I think some of it for sure is. And one thing I do want to preface too is I probably should have
01:10:23.040
also mentioned some of those compounds I do think are useful. Yeah. Well, we talked about it. Yeah.
01:10:28.140
Some of them have utility and I think are a shame that they're banned or harder to prescribe now or
01:10:33.900
get or what have you. Some of them, I feel like had no use being sold to begin with. And then some
01:10:39.400
are things I'm sad to see. Did we talk about CJC 1296 last time? Yeah, we did. And what was the
01:10:45.560
upshot of it? It is a good GH RH analog. So it works quite well in conjunction with growth hormone
01:10:53.940
releasing GH secretagogue that will essentially enhance the output of growth hormone concurrently.
01:11:00.220
So it's not bad. It just never made it through its pipeline. I think Tessa Moreland is superior for
01:11:05.520
that purpose. And Tessa Moreland is still okay. Yeah, it's approved for lipodystrophy and presumably
01:11:11.480
it's still going to be prescribed and sold. I don't know if they're going to clamp down on the
01:11:16.040
compounded version. You can only somehow get a pharma version. I don't even think I've ever seen,
01:11:21.260
I think it's called a grifta is the actual pharma version. I don't think I've ever seen it.
01:11:26.240
Probably way too cost prohibitive to even see the light of day, but that will continue to be prescribed.
01:11:31.280
And BPC 157 was kind of a VEGF analog. Yeah, that one is interesting because it's like pro
01:11:38.940
angiogenics that they're going to be pushing the whole, it's going to cause cancer angle or it
01:11:43.620
might. So we can't really get behind it, which understandable if it didn't make it through its
01:11:47.400
trial. So I get it at the same time, it sucks though. Cause it's like, we've all used it or know
01:11:52.720
someone who's used it, who's had benefit from it with perceptively like no downside, at least that
01:11:58.380
we can see acutely. So that's a tough one to see go for sure. But yeah, I think a lot of it is
01:12:04.020
hype, sexy new thing. Oh, this mechanism that's never been targeted, like it inhibits myostatin or
01:12:10.520
it does this or it does that, you know, there's an array of different compounds that do different
01:12:13.900
things that don't have FDA approval. So you want to be the first to be in a performance enhancing
01:12:20.280
advantage position relative to other people too. Even if you're not a professional athlete,
01:12:24.320
everyone wants the competitive edge or better focus, better muscle growth, better body composition,
01:12:31.300
understandably so. But it's not clear that these things really do that much in terms of performance
01:12:36.640
enhancement. When you consider testosterone, for example, which has enormous performance enhancement,
01:12:43.540
do any of these other peptides even come close? I would say in terms of like hard lean body mass and
01:12:50.260
strength outcomes. No, definitely not. That's part of the thing that sort of fascinates me is all of
01:12:56.000
these things are so marginal in their benefits. What would be interesting if there were infinite
01:13:00.600
resources would be to do clinical trials for specific use cases. I would actually be very
01:13:06.380
interested in seeing a clinical trial of BPC for specific type of injury recovery where there's a
01:13:12.380
really clear use case. We're going to do an eight to 12 week trial in post-operative orthopedic
01:13:17.580
patients where, boy, if there's one time when you want to see more VEGF, that's probably it.
01:13:23.460
And let's compare that to a placebo and actually see, are we getting quicker recovery? And if so,
01:13:30.080
maybe that becomes a use case for it. I mean, maybe in part, that's the challenge here. And
01:13:34.260
I don't know what the right balance is for something like the FDA to strike, but they've clearly had
01:13:39.420
enough of kind of the wild west. Yeah. I do wonder what really brought it to their attention. If there
01:13:46.240
was some like, it must've been our podcast. Yeah. There's something presumably that brought to their
01:13:51.960
attention. This is being, I don't know, mass marketed, misused. These aren't even approved
01:13:56.760
compounds. What's going on. And let's go down the laundry list of which ones have FDA approval. Okay.
01:14:02.060
That's pretty easy to exclude those. And the rest of them are gone kind of thing. So there's definitely
01:14:06.680
been an uptick in just haphazard promotion to them because it sucks because some of these do,
01:14:12.360
even though they don't have impactful outcomes on muscle growth necessarily, and like ergogenic
01:14:18.540
outcomes that are sport performance enhancing blatantly from a rehabilitation standpoint, or
01:14:25.540
potentially even a longevity standpoint, not saying any of them do definitively, but like
01:14:30.620
some of them have promise and had like really interesting outcomes in rodents. That would have
01:14:36.100
been nice to see what happened in a human's play out. Now, granted, if they got halted in trials,
01:14:40.660
probably wouldn't have ever happened anyway. So it's just random people taking it, but yeah.
01:14:45.880
You mentioned myostatin a second ago, which of course reminds me of something that's been going
01:14:50.740
around social media lately, which is this interesting discussion about a gene therapy for
01:14:56.260
folistatin. So for folks listening to us who haven't been following this, I guess there's a gene therapy
01:15:02.500
out there where you introduce a vector to somebody and I don't think you fully silence, but you clearly
01:15:09.720
attenuate actually, no, I'm sorry. You activate the gene for folistatin that makes more of the
01:15:15.560
folistatin protein, which inhibits the expression of the myostatin gene, or maybe inhibits the protein
01:15:23.100
myostatin one or the other. And this of course is theoretically interesting because of what we know
01:15:29.920
about the actions of myostatin. When I think back to images that stand out from my first year of medical
01:15:36.420
school, clearly on the top 10 list, you haven't even said it. I already know what you're talking
01:15:40.840
about. Yeah. You know what I'm talking about, right? Cause this is still like more than 25 years
01:15:44.000
ago. I still remember sitting in class when they showed the myostatin knockout mice and cattle.
01:15:51.180
And do you want to just tell people what a myostatin knockout looks like?
01:15:55.140
It produces a double muscle phenotype is what they call it. And if you look at these cattle,
01:16:00.300
it's like, you would think it's Photoshop by how absurd it looks. This is like the Mr.
01:16:04.180
Olympia of cattle, essentially. Like it would be no chance. Anyone would come close in cattle sport,
01:16:09.920
whatever. And in the mice, same deal. They have literally, they call it double muscle essentially.
01:16:16.160
Cause it's, you literally have double the muscle fibers as the wild type. Yeah. The reference.
01:16:22.340
And I remember like the chickens, the mice, the cattle. I mean, it was truly remarkable.
01:16:28.200
There's this dog too. Super Jack dog. I forget what type it is, but she has the same mouse.
01:16:32.940
So my roommate and I spent the rest of medical school just talking about, we've got to figure
01:16:38.200
out a way to inhibit our myostatin. Yeah. Yeah. Okay. So apparently now someone's working on this
01:16:43.220
and they're claiming that for just, I don't know, $25,000 for your first shot and maybe 25,000 for
01:16:49.780
every subsequent shot, you can get a gene therapy that will activate and produce more of a protein
01:16:58.420
called folistatin that inhibits myostatin. And so that should be good, right?
01:17:03.420
Yeah. Yeah. It seems like at least in the literature in animals, you see the myostatin knockouts and you
01:17:10.720
see this double muscle phenotype. You would assume there is actual rodent data too, where you see
01:17:16.520
folistatin administration does enhance muscle. Like it does happen. And I guess as a result of that,
01:17:22.760
a lot of these research chemical companies were very quick to come out with freeze-dried,
01:17:28.540
lifelized, folistatin product that had one milligram per vial and you would buy it for,
01:17:34.560
you know, hundreds of dollars. And then you would basically like shoot a vial a day or
01:17:39.080
something of that nature and spend thousands over the course of a cycle, which was based on no data at
01:17:46.420
all. How did this peptide get created? Is this an FDA approved drug or is this one of those?
01:17:50.820
No, it was like, we know what the chemical structure is. Let's go get an Alibaba chemist.
01:17:58.560
And technically, yeah. Okay. So got it. So you've got this kind of gray market folistatin product out
01:18:04.320
there. Yeah. And this one is not gene therapy to be clear too. It's literally just-
01:18:08.060
Yeah. No, you're actually injecting the protein.
01:18:09.380
Yeah. Yeah. So you'd literally get bacterial static water, shoot it in, swish it around until it's
01:18:14.360
mixed and inject it in yourself. And the half-life is like, I don't know, a couple hours. So you'd have to
01:18:19.720
inject them multiple times a day to have it be stable in your blood to actually get the effect
01:18:24.360
presumably. And essentially the outcome that we saw in the bodybuilding world, because this has
01:18:29.140
been around for a decade plus at this point, if not decades, was not really anything. There'd be
01:18:35.640
the random outlier who's like, I gained 20 pounds in two days. And it's like, okay, bro. And everyone
01:18:40.240
else got nothing essentially. I think you couldn't help but think that guy was probably selling it or
01:18:43.860
something. So anyway, not that impressive. And we just assumed it didn't work. And then
01:18:48.820
we come to find out that there's these viral vector studies going on behind the scenes and rodents.
01:18:54.780
And there was one in humans, I believe too. And more recently, there's this bacterial vector
01:19:01.220
version of it, which is being created. A lot of big names are getting it and stuff that Brian Johnson,
01:19:07.360
biohacker dude got it. And I've yet to see any actual metrics of before and after muscle growth or
01:19:13.700
anything of that nature, he's kind of just produced. Apparently his folistatin increased. So
01:19:18.500
presumably it's actually doing something. It's just, is that outcome of more folistatin actually
01:19:24.640
binding enough myostatin to have an effect that is worthwhile.
01:19:28.920
By the way, how is folistatin measured? Is there a certified assay for measuring folistatin?
01:19:34.300
I don't think so. I think they're using their own like internal measurement as far as I know. So
01:19:39.300
they have like their own assay that they've developed. So I don't really know.
01:19:42.840
There might not be a validated assay for measuring this hormone, but this protein rather.
01:19:46.800
Yeah. I couldn't say for certain that that's actually measuring it correctly. So assuming
01:19:51.320
that it is, it is increasing it. And then is that actually doing anything? The picture that you got
01:19:56.640
sent obviously looked pretty impressive. Objectively to me, it kind of looks like it has some of the
01:20:01.420
hallmarks of fitness industry angles and like lighting manipulations and stuff.
01:20:06.220
Just to back up for a moment, this discussion came out of a patient sent to me something off
01:20:11.980
Twitter, which was like kind of a before after of someone who had done this gene therapy,
01:20:17.660
but just for folks who aren't in the space, including me, although I feel like I kind of
01:20:22.780
can see the bullshit when I look at it, but walk through the, how do you take a pre and post photo
01:20:29.560
and create the most difference? Cause you've actually sent me pictures before of pre and post
01:20:35.440
on the exact same day and they look totally different. So clearly there's no biologic
01:20:40.180
difference, but there's a huge aesthetic difference. So what are the tricks that people
01:20:43.740
use to manipulate photos? Shy of just straight up Photoshop.
01:20:47.340
Anybody watching has probably had a cheat day. And when I say cheat day, I mean just the day you go
01:20:51.480
off the rails and eat whatever junk you want, where you had horrendous distension of your stomach to
01:20:57.980
the point where it almost looked like you're holding an alien baby or something like that is not
01:21:02.580
uncommon for us to have all dealt with at some point. Some really bad digestive problems. And
01:21:08.100
a lot of times these before and afters are not actually shot. I'm not saying this is the case
01:21:12.980
with this before and after, by the way, I'm just saying in the fitness industry, pretty typical,
01:21:16.820
especially years ago when they could get away with more egregious examples of this. And it's gotten
01:21:22.100
a little bit better now, but now there's Photoshop and all that shit. But anyway, you could,
01:21:27.420
and what is typical, people would take the after shot and they would get their pump.
01:21:31.180
They would make sure that they have heavy downlighting. They'd be like oiled up potentially
01:21:35.700
in the perfect circumstance, essentially for even temperature. Vasodilation changes just in
01:21:42.040
temperature very massively. So you want a higher temperature presumably?
01:21:46.880
Yeah. So if we went in your gym and we cranked the heat and I did five sets of curls, five sets of
01:21:52.540
something, I could get my arm vascularity to look unrecognizable compared to what it is now.
01:21:58.720
And then I could walk outside and you would see me just like disintegrate in front of you essentially
01:22:03.020
as it all vasoconstricts from the cold. So that is something that is very abused in the before and
01:22:10.160
after kind of transformation shots where they will achieve a transient look that is not representative
01:22:17.420
of them walking around. And it is certainly not representative of the complete opposite
01:22:22.540
circumstance that they do the before shot. And so they will do everything perfect and take their
01:22:28.700
after shot, which is as good as they can possibly look with all circumstances accounted for, which
01:22:34.120
is actually shockingly, as much as you say, you're aware of it and you know how, what goes into it and
01:22:39.340
you can call obvious bullshit. You'd be shocked how many people in the fitness industry still can't do
01:22:43.360
that. They'd be like, how'd you gain 30 pounds of muscle in like three weeks? It's like, dude,
01:22:47.160
you should know this. You watch these videos all the time. Come on. So anyway, and then you would
01:22:52.380
take the before shot and depending how egregious you want to make it, you, you know, go in much
01:22:57.800
worse lighting after you have successfully downed four to 5,000 calories of processed garbage food.
01:23:05.940
So you actually are swelling. You're so inflamed.
01:23:09.020
Yeah. Think of everything you could do to look as horrendous as possible, even down to the facial
01:23:13.340
expression of looking disappointed on camera with how abysmal your physique is.
01:23:17.160
And of course you deliberately stick your gut out to exaggerate it.
01:23:20.620
Yeah. It's not hard because you're so distended too. It's just like exaggerated. Plus you're
01:23:25.660
distending it. Plus you're looking disappointed and you're not flexing. Yeah. You're rolling your
01:23:30.380
shoulders forward instead of rolling them back. You have no pump. You just walked outside. You've
01:23:34.900
been hanging out eating shitty all day. There's a lot of things that it sounds like these factors are
01:23:40.240
not significant enough to make this big of a difference until you see them all stacked.
01:23:43.780
Yeah. And if you haven't gotten to 10% body fat or less, I can't highlight enough how dramatic it can
01:23:51.000
really get. Like sometimes you will see a guy who's 150 pounds who shredded in the perfect lighting
01:23:56.860
circumstances. The guy could look like a Mr. Olympia competitor through angles, lighting,
01:24:02.380
et cetera. And then you see him in real life with a t-shirt on. You're like, dude, do you even work
01:24:05.920
out? That's how dramatic it gets. I don't know why people don't. Well, I think I know why I think a lot of
01:24:11.380
people have never got there to know what the difference is, but when you're lean, it's a pretty
01:24:16.640
dramatic how much you can fudge things. And it is abused to high hell by people who want to sell
01:24:22.020
things. So anyway, in this circumstance, I'm not saying that's what happened. Like there was a pretty
01:24:26.060
impressive before and after for what is supposedly, I don't know if he used drugs alongside it. That
01:24:32.120
wasn't really at least clearly disclosed that the glance I took at the caption, maybe it was,
01:24:36.780
but there was no change in nutrition and exercise supposedly. He looks quite a bit better, but the
01:24:43.780
sniff test was a little bit like, eh, you're kind of like sticking your head out a bit. Are you trying
01:24:48.420
to look worse? So I don't know. He seems like a nice guy. The guy who's kind of like at the forefront
01:24:52.980
of speaking about its utility and all the viability it may have in regenerative medicine. And there's no
01:25:00.940
viralizing outcomes either because it's not acting through AR. It's like an independent mechanism.
01:25:05.440
So it sounds cool in theory, but the outcomes we see at least clinically have not been impressive
01:25:14.440
enough for me to be floored by it. So I'm not sure if the transformations we see online are
01:25:20.440
typical or if they're a little bit exaggerated or what, but I think there's some level of potential
01:25:27.380
exaggeration that comes with this stuff. Yeah. And how much muscle mass are they? Cause they did a
01:25:33.080
sort of open label trial, didn't they? The phase one. Yeah. Yeah. So they, I don't know if it's
01:25:38.440
published now or if it, I think he said it will be submitting it. I don't know if it's been accepted
01:25:42.800
anywhere. Yeah. So it looks like the lean body mass gain was statistically significant, but not
01:25:52.080
that impressive from what I recall. It was like two pounds. Yeah. Something like that. And then
01:25:57.360
what do they have like inflammation markers, which were kind of like stay the same.
01:26:01.800
The only P values to my recollection that were statistically significant was an increase in lean
01:26:07.280
body mass. You said to the tune of about two pounds, I think there was something else. I don't
01:26:12.040
remember what it was. A slight reduction in body fat, intrinsic biological age. I don't know if you want
01:26:18.680
to speak to the validity of those tests. Cause I think you're, there is none. Okay. So those are
01:26:24.900
meaningless. I think there was about a 1% decrease in body fat that was statistically significant.
01:26:29.980
If my memory serves me correctly, it didn't seem like the controlled for exercise or anything. So
01:26:34.440
I don't really know how, what the takeaway is. I was surprised at how little the effect was
01:26:41.720
if this mechanism matters and it might not matter. In other words, it might be the case that while
01:26:49.280
knocking out the myostatin gene at birth produces a profound muscular phenotype,
01:26:57.740
attenuating the gene later in life might not do much. I did ask one of my analysts to look this up
01:27:02.940
today. She found an experiment where they took mature mice, call it like a two-year-old mouse,
01:27:08.320
and they did a near complete block of the myostatin gene. So not a hundred percent knocked out,
01:27:16.260
but like more than 99% of the mRNA was deleted. And it did increase muscle mass in the mice by about
01:27:26.240
25%. But 25% increase in muscle mass is significant, but that's at basically completely knocking out
01:27:32.700
myostatin. Whereas if you do that at birth, as you said, you're going to more than double muscle
01:27:37.060
mass. So that also suggests that best case scenario, if you did this in a developed individual,
01:27:43.600
you're going to get big results, but it's not game-changing. And of course, doubling or tripling
01:27:48.660
polystatin levels, which kind of indirectly work on this pathway, it's possible this would have no
01:27:54.460
effect. I mean, you'd have to see this studied more rigorously, potentially with people who don't
01:27:59.380
have a conflict of interest, which is also something you have to be careful of when you look at this
01:28:03.340
type of literature. But I don't know, I guess I wouldn't bet on it would be my two cents.
01:28:07.340
Apparently there's a phase two trial that is happening either in Canada or Japan. And then
01:28:13.240
there's six month results that are more impressive that they're highlighting.
01:28:18.820
And these phase two studies are specifically for sarcopenia. So I'm assuming they're recruiting
01:28:23.740
people over 60. Look, if you could add five or 10 pounds of muscle to somebody over 60,
01:28:29.560
that would be really impressive. Do we have any insight into how much training stimulus is required
01:28:33.860
to produce these effects? I don't know what their phase two trial is going to encompass or the
01:28:40.220
inclusion criteria or anything, but I don't even know if they're using training in the phase two.
01:28:45.780
To me, an interesting study would be a placebo, a placebo group that trains,
01:28:51.560
a treatment group that does not train, and a treatment group that trains. That would be a very
01:28:58.100
interesting comparison. Yeah, no, for sure. Because I'd love to see placebo who train,
01:29:03.860
two, no stimulus treatment, you get two very elegant comparisons with those three groups.
01:29:09.700
Yeah, that would be great. And like this stuff has definitely been hyped for years. So if there
01:29:14.820
is a way to actually get the answer finally, like does folistatin work in humans and produce an outcome
01:29:21.280
that is something you could avoid anabolics entirely for the androgen sensitive that might
01:29:27.240
otherwise need anti-catabolic action in later life or in a burn scenario or whatever, like that seems
01:29:33.620
like pretty useful to flesh out because SARMs definitely didn't pan out the way pharma had hoped.
01:29:39.460
Now, what's interesting though is wasn't there a trend towards, didn't everything move in the wrong
01:29:45.160
direction? I don't know if it reached statistical significance on lipids and metabolic markers.
01:29:50.060
Yeah, I don't really get it. Rest in glucose was elevated. Insulin went up. HDLC went down.
01:29:56.940
Yeah. Trigs went up. LDLC went up. So all of those things kind of moved in the direction you would not
01:30:01.640
expect if this were beneficial. One thing that is weird is this folistatin, when I was looking it up,
01:30:08.340
I kept seeing the FSH inhibition statements. And I was like, is this some sort of like precursor? And
01:30:14.360
I'm misinterpreting the acronym because surely it's not intertwined with follicle stimulating hormone.
01:30:18.620
But it turns out it actually used to be called follicle stimulating inhibitor hormone or something.
01:30:25.420
And it's like primary mechanism that was known was how it would inhibit the production of FSH at the
01:30:30.940
pituitary, which is really weird that that is something that apparently the isoform used in
01:30:37.340
this vector is one that is less specific for that component of what folistatin typically does
01:30:44.020
endogenously. But that is, I don't know if there's some off-target mechanism that is resulting in the
01:30:49.300
glucose aberrations or whatnot. But like, I have no idea what would be causing it.
01:30:54.240
Well, it'll be interesting to see the phase two, as you said, and hopefully they
01:30:56.460
study it with a large enough sample size that you can sort of make sense of it.
01:31:00.400
Anecdotally, there are some like big names that are using it. And I don't know if it's placebo or what,
01:31:04.880
or if some of them are getting good results. And it's just like outliers. I don't know. I don't really
01:31:08.380
know. Yeah. I got to tell you my interest in hearing about what celebrities are achieving
01:31:13.620
using any sort of treatment is zero. And I'll tell you what, just for people to understand this
01:31:18.480
nonsense, it doesn't matter what celebrity X achieves using drug Y. If you have no idea how
01:31:26.120
their diet has changed, how their exercise has changed, how many steroids they're taking alongside
01:31:30.140
of it, whether they're being paid to talk about it, like all of these things so dramatically impact
01:31:35.820
what message gets filtered down to people that I just don't think we could work hard enough to
01:31:41.440
increase the scientific literacy of people to help them make sense of this.
01:31:45.700
Just notable, by the way, for anyone watching, who's not a member of the drive, like this is why
01:31:50.240
I pay for your membership is like the trust factor I have in your stuff is like above and beyond
01:31:56.020
any piece of content I consume. Essentially, like there's no bias, there's no financial incentive,
01:32:00.520
even to the degree of you don't push companies you're an investor in, like it is just
01:32:05.400
legit facts, totally unbiased. Here is Peter's opinion with no incentive, inherently manipulating
01:32:13.340
my opinion whatsoever. Like so I just want to say, I really appreciate what you do. And anyone who's
01:32:18.260
not a member, you should go be a member right now. Thanks very much. I really appreciate that.
01:32:23.200
Okay, I want to pivot a little bit to talk about something you made a video a while ago,
01:32:27.040
I thought it was a great video. I don't know how long ago you made it, though. It was all about
01:32:31.300
appetite suppression tricks that bodybuilders use. And I think the purpose of the video is,
01:32:38.500
hey, for those of you, most of you who are not bodybuilders watching this, who still want to
01:32:42.820
shed a few LBs, these are some tricks that can be used, dietary tricks. Do you remember some of
01:32:49.460
that list? Yeah. And I do want to preface when I say this, that when bodybuilders are trying to get
01:32:56.120
very lean, it gets to a point where you're pulling out all the stops to an extent whereby it's not
01:33:01.960
necessarily reflective of what is the optimal healthy diet. Sometimes it's to the extent of
01:33:08.360
short of any attempt at micronutrient density, how do I hit my protein and satiate myself to the
01:33:15.060
maximum extent and fuel my training with enough carbs and have enough fat that I don't have hormone
01:33:19.840
suppression? Those are the metrics once you get to the end of a dieting phase. Now, that's not
01:33:24.800
necessarily indicative of what everyone's going to do because most people just want to see
01:33:28.640
a hint of abs for the first time. So you don't need to take this to the extreme.
01:33:34.400
I interpreted your video as this is the full suite of things you have. Sure. You wouldn't do all of
01:33:40.020
them simultaneously. You kind of pick and choose from this list with what works. Correct. I guess I
01:33:45.180
just definitely want to make sure because people watching your stuff know what high quality food is,
01:33:50.500
and I do not necessarily advocate for these in all circumstances, but diet soda, quite useful for
01:33:57.200
calorie restriction, in my opinion, for maintaining some satisfied sweet tooth. I think Lane has published
01:34:03.400
a really good video recently highlighting that even compared to water, I'm not suggesting replace it with
01:34:08.420
water, but in a state of calorie deficiency, if you have a craving, you're probably better off drinking
01:34:13.640
a diet soda than you are eating some calorie rich fat laden sugar bomb dessert. Like even some of the keto
01:34:21.540
treats that you see that are marketed as healthy and diet conducive. Oftentimes, look at the nutrition facts,
01:34:29.480
you'll note the calorie component is horrendous. So just because the sugar content might be low, the fat content
01:34:36.480
proportionally to make it taste good is far more destructive to your actual body composition goals. So that is
01:34:42.860
something of note as well. Some of the first things I do typically that are low hanging fruit are try to
01:34:48.160
maintain the same volume of food on my plate, but just replace with more calorie light options. So as much
01:34:56.820
as I love the micronutrient density of red meat, and it is one of my go to's, I will consider swapping
01:35:03.320
some of it to chicken breast, for example. Not necessarily saying to do that long term, but it is certainly an easy
01:35:09.620
way to maintain if I'm having a six ounce portion of meat in a meal to hit my protein needs, having a
01:35:16.500
lean chicken breast as opposed to my ground beef that I had at the grocery store, the difference in
01:35:22.340
calorie to protein content is pretty significant. One of the first low hanging fruit things I do is see
01:35:27.980
how can I replace what to me perceivably is the same amount of food, but just with lighter options.
01:35:35.200
So that will be going from a fat filled Greek yogurt to maybe a more fat free Greek yogurt. And
01:35:42.260
it doesn't taste exactly the same as you remember it, but it's pretty damn close. And the calories are
01:35:47.440
perhaps a fraction as much, and you're still getting proportionally the protein you need.
01:35:52.180
Swapping some red meats to whites, eggs going from some eggs with egg yolks. If you sprinkle in some
01:35:59.220
egg whites with it, as opposed to just all whole eggs, you can still get yolks in and get your
01:36:04.820
micronutrients. But it almost tastes indiscernible different when you have just maybe like one or two
01:36:10.720
of them replaced with egg whites, as opposed to the whole egg. There are little things that are
01:36:15.500
just noticeable, but not enough for you to consider it. Oh my god, I'm in a deep deficit right now. And
01:36:20.760
it's like, I'm starving. You almost don't notice that in itself, just even three things I mentioned,
01:36:26.420
you probably could have chopped off 500 600 calories. An egg is 80 calories per large egg, I believe
01:36:33.660
could be even higher, depending on how large it is. And then an egg white for the proportional
01:36:37.360
amount of protein, I think is like 30 off the top of my head. Could be wrong on that. But something
01:36:42.320
like that. Chicken breast, I think it's like 30 calories per cooked ounce, depending on, you know.
01:36:47.860
This is why I like wild game, because you're still getting red meat, but it's super lean.
01:36:53.340
Yeah, this is one thing I was going to ask you on our podcast for my channel too, is like you pound
01:36:57.780
these venison sticks that are so lean and great. How would you, as a budget-friendly person, go about
01:37:06.560
getting your protein with the most lean cuts? It's pretty cost prohibitive to get the really good
01:37:12.360
bison, venison, stuff like that. One option is, if you want red meat and you want to build it, I think
01:37:17.840
you just go hunting, right? If you shoot one large deer, one elk, that's going to feed your family
01:37:25.120
for more than a year. See, this is unconventional advice, but that is like actually practically
01:37:30.500
applicable advice for what is budget-friendly. Yeah. And by the way, people would say, oh my
01:37:35.840
God, like how do you shoot an elk? I mean, you know, it's impossible to get elk tags to shoot
01:37:40.340
big elk. Well, guess what? It can be a cow elk, like a cow elk, a female elk. Those tags are over
01:37:45.960
the counter. Anybody can get them. You're not trophy hunting. The states regulate how much you can hunt.
01:37:51.440
You get incredible meat from the cow. I would argue that's the healthiest thing you could eat,
01:37:55.940
frankly, is wild game because these animals are completely unstressed. So I think those are
01:38:00.880
options if you're sort of doing it on a budget because the amount of meat you would get out of
01:38:05.000
a cow would more than feed you and your family for a year. What would you think? I don't even know if
01:38:10.980
this is the right question to ask because I've never hunted. So I don't know what this looks like
01:38:14.100
as far as the cost to get what you need to hunt with, whatever licensing you need, how many states
01:38:20.560
this is viable in? And then also skill level. Does it take a long time to even get to a point
01:38:26.520
where you could successfully achieve? The big divide is if you wanted to bow hunt versus rifle
01:38:31.300
hunt, it's much, much quicker to get there with a rifle than a bow. But also I truly believe rifle
01:38:36.480
hunting is more humane. A person who's a really good shot, believe me, it doesn't take that long to
01:38:41.100
become a really good shot with a rifle. You would be able to shoot an animal within inside 300 yards or
01:38:46.020
400 yards and the animal would die immediately. So there's no suffering involved. That would not be
01:38:51.120
a terribly expensive proposition. Now maybe the first year it is, but remember you amortize the
01:38:55.560
cost of your learning and buying a gun and things like that out over the cost. I mean, I'd have to
01:39:00.920
sit down and do the calculation, but I think that would be less expensive than if you were spending
01:39:05.360
that much money on meat for sure. Cause you're going to get thousands of dollars worth of meat from
01:39:09.900
that. Definitely sounds better than what I used to do, which was buy a really shitty frozen chicken
01:39:15.380
and boxes at superstore. I'm sure I said this before on podcasts, but the more I've eaten and
01:39:21.520
migrated my diet more and more towards wild game, the less I can really tolerate. I mean, I can't eat
01:39:26.360
anything that's farmed. Even chicken. Chicken is just so nauseating to me in general, but anyway,
01:39:32.720
it's just everyone's palate is somewhat different. Yeah. That's one of the problems with getting exposed
01:39:37.500
to better food too, is you develop this refined palate where the stuff you used to get away with
01:39:41.980
that was super budget friendly and you lived on and you thought was fine now tastes horrendous.
01:39:47.860
But anyway, aside some of the things like I think the meat discussion is definitely useful. I hadn't
01:39:55.280
even thought of that. So that's worthwhile to note. What's your advice to somebody who's trying to lose
01:39:59.540
weight, but in a sustainable way, in some ways when bodybuilders are doing it, it's not really
01:40:04.140
sustainable because they're really starving themselves down to a competition. And the way
01:40:10.020
that they're eating during that period of time, it's so catabolic that they're destroying their
01:40:15.540
endocrine system along the way, but it's short lived and they're going to refeed when they're done.
01:40:20.420
And so while we can talk about all of the different things that they might stack and do all simultaneously,
01:40:25.500
what's your view on the sustainable way to lose 10 pounds and keep it off in terms of deficit?
01:40:32.420
I think your perception of what bodybuilders do as far as aggression towards their diet
01:40:39.000
is hinged on their final outcome and how steep it is to get there cumulatively. But the way they
01:40:47.400
arrive there, no one is more mindful of preserving tissue than bodybuilders.
01:40:52.100
So in other words, they're not creating huge deficits at any one point in time.
01:40:55.660
Eventually they are at the point that they absolutely need to, but they're more careful
01:40:59.760
than any human I know. Oh yeah, I would believe. So if you were to try and take away from a
01:41:04.660
bodybuilder, how would I apply this when they're stepping on stage at literally diced to the socks,
01:41:10.040
5% body fat. It's not that you're getting there. It's that you're stopping at the eight week out
01:41:15.200
from competition mark of a bodybuilder, maybe not eight, maybe like 10 or 12, but the process they
01:41:21.000
took to get even there was very staggered, calculated.
01:41:25.640
And by the way, 10 to 12 weeks out, what's their body fat relative to that five they're going to step
01:41:31.180
It depends at what level and how on track they are, but some of them are starting at like 12% body fat.
01:41:38.380
Everyone has different goals of what they consider good. So maybe this is like my skewed
01:41:41.900
fitness perception saying 10 week out bodybuilder is what you should shoot for. But just in general,
01:41:45.820
the process they take to get from their peak body fat percentage to stage lean, no one is more mindful
01:41:53.760
of titrating accordingly the macronutrient and micronutrient input to sustain training volume too,
01:42:02.020
because they need to actually make sure their training doesn't deteriorate. Because if it does,
01:42:05.880
they're going to lose tissue. So taking from that, you see them at least hitting one gram per pound
01:42:16.500
Unless there is some like, maybe on the week of, they're already at their target body fat.
01:42:22.320
And then at that point, they're trying to do tactics to make their stomach as
01:42:26.280
not full of anything as possible. So what they do on the last week doesn't really count.
01:42:32.580
But up until a week out, they would still be taking one gram of protein per pound of body weight.
01:42:37.260
And to your point, at this point, you can't be doing that with steaks because it's way too caloric.
01:42:42.000
So you are on the chicken breast protein powders.
01:42:45.820
Depending on the person though. And I guess it depends on, again, the quality of your meat,
01:42:49.580
because it's like, I've seen the macros on your venison and it's...
01:42:53.980
Yeah. So basically the staggered approach you want to take is that you don't really want to lose more
01:43:00.680
than, I think typically it's like 1% of your body weight per week is a general rule of thumb,
01:43:06.180
which is, I guess could be, depending how obese you are, could be a little bit aggressive. But
01:43:11.060
even let's just say a pound a week maybe is like maybe a more reasonable target. But in general,
01:43:17.580
if you are, and this is kind of a, perhaps a more applicable cookie cutter recommendation,
01:43:23.980
Which I think everyone would essentially agree with in a deficit to sustain
01:43:27.160
tissue, lean tissue, muscle mass. Then from there, you want to be whatever your maintenance
01:43:33.180
calories is, which is, it might take a little bit of finagling to figure out what this is when
01:43:37.580
you've never done it before. But there are calculators online that roughly ballpark give
01:43:41.880
you what will be plus minus 300 calories or something of what it takes to stably hold your
01:43:48.920
body weight. If you ate that diet, it wouldn't go up or down. What I do typically is I take that
01:43:55.240
number and I say, use your exact diet for a week with this calorie amount. Like this is your diet
01:44:02.200
model and this is your totally calorie goal for the day. Eat exactly this every day and then see
01:44:07.680
what the average is at the end of the week. Because just going by daily fluctuations could be wildly
01:44:13.080
different. You might jump up or down based on water, based on food volume, based on if you took
01:44:17.720
a dump or not. By the way, when do bodybuilders come off creatine? They don't. They'll take creatine
01:44:22.960
to the stage? Yeah. They used to think you should come off because it's bloating. I'm sure Lane would
01:44:27.120
tell you the same. But most of the water weight is in the muscle. Yeah. It is helpful for cosmetic
01:44:31.660
appearance and for sustaining training performance. Got it. So it's anti-catabolic. Interestingly enough,
01:44:38.120
it's one of the only natural compounds that may inhibit myostatin too. So it has that upside and
01:44:44.040
it's all the things it does from a neurological standpoint, perhaps fertility. It's even used for
01:44:49.020
depression now in women at like 10 plus grams or something, which is crazy. So a lot of use cases
01:44:54.560
are coming out, but overall, we all know it works for muscle, for performance in the gym, as well as
01:44:59.920
volumizing the muscle. Would you say creatine is hands down the best over-the-counter supplement for
01:45:06.220
performance? For sure. Can't think of anything off the top of my head that would be superior
01:45:10.780
depending on your sport though. Yes. If weight is everything, if you're a cyclist or a runner,
01:45:17.140
the downside of the extra five pounds of lean mass is perhaps, yeah, but I'm making sure you have some
01:45:22.440
sort of number you're going to adhere to and you know how to measure every day, which basically is
01:45:28.500
just reading every nutritional label you have and becoming intimately aware of what you're ingesting.
01:45:32.440
If you put something in your mouth, you count it regardless if it's a sauce, regardless if it's
01:45:37.360
a drink, regardless if it's a lick, you count that shit. Do most bodybuilders use like an app to do
01:45:43.020
this or can they just keep track in their head after a while? After a while, they are so in tune
01:45:48.080
with it. You can look at a piece of meat, know how much it's going to shrink after cooking, know how
01:45:53.200
many ounces it is, how much that equates to in protein, calories at a high level. It becomes so
01:45:59.180
ingrained that you don't even need to track it because you can literally look at it. Maybe you'll
01:46:03.960
keep the calorie count and the protein count, but you know what you're looking at and it can just
01:46:08.300
write it down quick. You don't have to go look up and cross-reference, you know, on my fitness pal,
01:46:13.000
what is a chicken breast one ounce cooked equal? So you can at least look forward to, even though it's
01:46:19.020
cumbersome and arduous at the start, eventually it becomes so habitual, you'll just know it. So you have
01:46:24.340
a target calorie amount and you eat that every day for a week and you see if your weight goes up or
01:46:28.680
down. And if it goes up, you know, you're getting a bit too much. If it goes down, you know, you're
01:46:32.880
in a deficit and you decide from there is the weight loss too fast. If you lost three pounds in a week,
01:46:38.020
perhaps it's too fast and you want to kind of like titrate it back up a little bit, but ultimately you
01:46:43.060
can kind of shoot for once you know your maintenance, some amount of calories where you're dropping
01:46:48.300
300, I feel like is a good deficit to start at because ideally, and this is kind of the whole
01:46:53.980
general approach without getting way too boring for everyone is you want to keep your protein where
01:46:58.880
it needs to be, which is a gram per pound. You want to have enough carbs to fuel performance,
01:47:04.860
which depending on what sport you're doing can vary, but without getting too complicated,
01:47:09.040
a good split a lot of people follow is 40% protein, 40% carbs, 20% fat. And this is kind of like a ratio
01:47:15.560
that allows you to sustain hormone production and have some amount of fat that supports it.
01:47:21.580
carbs for some level of gym performance and then protein for hopefully hitting your goals. And
01:47:28.060
it'll depend on the person and modulate accordingly, but that's just a general framework people can start
01:47:33.840
with. So that's a pretty low fat diet ish. The fat and the protein would typically stay around
01:47:40.820
neutral and you would typically lower the carbs accordingly depending on how intensive your
01:47:46.560
exercise regimen and sport is. But in general, I feel like that's like a minimum amount of fat that
01:47:52.200
would be no lower than that is kind of what I'm saying. What are some of the concessions a person
01:47:56.800
has to make to get that low in fat? I think I'm probably literally the last time I tracked my macros,
01:48:02.600
I was almost exactly one third, one third, one third between the three. And I didn't feel like I was
01:48:08.780
like eating a ton of fat. Typically when you are eating meat, you will achieve the majority of that
01:48:14.660
through the fat content of your meats. And it will depend how lean of the cuts you were getting,
01:48:19.980
how many eggs you were eating. But I'm just thinking like the olive oil on the salad and
01:48:24.820
stuff like that. Yeah. But I guess that's like, they're just cutting that out. Yeah. Like olive oil
01:48:29.740
on a salad is one of the first things I would be looking at as you probably just added what 200 to 300
01:48:35.020
calories to a big salad for sure, if not more. Yeah. So unless you're Brian Johnson or willing
01:48:39.960
to get like 25% of your calories from oil, probably not a bodybuilding conducive macro allotment.
01:48:47.600
Even though fat is satiating, it's nine calories per gram. Where do bodybuilders get the majority of
01:48:53.400
their fiber? Typically, it will be through veggies if they're having them. And those are going to be
01:49:01.700
proportionally lower calories, I suppose. But oftentimes fiber is not. I don't know. Some
01:49:07.220
of them use like supplements to axillium husk. I don't want to get into like a fiber debate necessarily,
01:49:11.580
because I don't even know like what the actual answer is there. But in general, bodybuilders
01:49:16.860
aren't really paying. Right. They're not optimizing for health if we believe fiber is healthy.
01:49:21.180
Yeah. And I'm not saying neglect it. Like I think that it is important. I'm certainly not saying
01:49:26.580
remove your fiber in order to achieve your deficit. I'm just saying that you can
01:49:31.020
proportionally get to your goals almost certainly by modulating carb intake essentially exclusively.
01:49:37.080
Typically. Yeah. And that's going to be in the form of starchy carbs then.
01:49:40.580
Yeah. And like you can modulate the type of foods you're eating too to accommodate
01:49:44.300
the satiety is ultimately the takeaway from me. Because when it comes to actually describing the
01:49:50.620
nutritional literature, I hate it as much as you, dude. It's not like something I like to talk about.
01:49:54.820
Oh, how much fiber should you keep in? I don't know, man. A decent amount, like some,
01:49:59.780
but enough that you can go to the washroom properly and it's some healthy amount. But ultimately what
01:50:04.840
I've seen in the bodybuilding space is modulating carbs up and down accordingly based on needs in
01:50:09.900
the gym and protein stays at an amount that is anti-catabolic or conducive to muscle protein
01:50:15.240
synthesis in a surplus. Fat is some amount that at least supports steroid hormone production
01:50:20.280
as much as you can tolerate. And then carbs is like the most performance enhancing macro in terms
01:50:25.280
of actually driving your performance outcomes in the gym, volumizing the muscle, having glycogen
01:50:30.760
topped out, et cetera. And from there, I would typically recommend a 300 deficit and literally
01:50:37.520
milk that. And that week prior to show, how many calories is a bodybuilder typically down to?
01:50:44.280
If they're stage ready and they're natural and like sub 200 pounds, like they might be down to
01:50:52.760
below 2000 calories potentially. If they're a top IFBB professional, Mr. Olympia competitor who weighs
01:50:59.220
260, they could be at 2,500, 2,600. It kind of depends. Which is interesting for many people listening.
01:51:07.060
That sounds like a lot of calories still, but you're saying given how big they are and that they're still
01:51:11.940
training pretty hard, but it's a pretty big deficit. It also depends how much they're willing to lean
01:51:17.180
into cardio because some guys will actually prefer to just diet themselves into the body fat and not do
01:51:24.540
any cardio because they just don't like it. Wouldn't recommend that though. Because one thing I have
01:51:28.520
learned over the years is from a nutrient partitioning standpoint, actually moving when you're eating is
01:51:33.720
going to produce a better body composition typically than trying to just diet the whole deficit.
01:51:39.840
So what we see even in like the IFBB with these top bodybuilders who are trying to not get fat as
01:51:48.020
they eat exorbitant amounts of food and they're on insulin and HGH and huge amounts of anabolics,
01:51:54.000
they are doing things like going for walks after they eat their meal, which is more potent than
01:51:59.360
metformin controlling blood glucose. Like they're actually making sure they are moving around and
01:52:04.060
actually shuttling nutrients as much as they can, even outside of the gym. Some are lazy and don't do
01:52:09.140
that, but the ones that are trying to make the most use of maximizing the calories.
01:52:13.680
I see. So the mobilization doesn't require that you're clearly not going to oxidize everything
01:52:18.400
you ate. Like if they just ate 800 calories, they're not going to burn 800 calories on a walk
01:52:22.960
of any duration, but just getting out there and walking, you're saying leads to better fuel
01:52:27.080
partitioning. Seemingly. Yeah. Interesting. And I think that is, and you could correct me if I'm wrong.
01:52:31.980
I mean, I've certainly anecdotally noticed the improvement in blood sugar.
01:52:34.800
Yeah. Yeah. Even for stabilization of like energy levels to like making sure you're not
01:52:40.420
hanging out on a couch with your spike blood glucose seems to be pretty impactful, not just
01:52:45.260
for mental performance, but also for partitioning and actually optimizing body composition too.
01:52:50.840
And that's an enhanced ranks at guys eating exorbitant amounts. But anyways,
01:52:54.620
backs of the layman in general, you're in a 300 deficit. You kind of milk that for all you can.
01:53:00.580
And by that, I mean the biggest problem. And I guess one of the biggest takeaways from this
01:53:04.740
whole discussion could be that the people who aggressively cut way too fast will end up losing
01:53:11.260
more weight off the bat, but they will end up in a state of adaption faster, whereby you are
01:53:18.260
basically going to not only expend less calories at rest via the depression of non-exercise activity
01:53:28.380
thermogenesis, which is like fidgets and moving with just like your everyday activities, you will
01:53:33.300
actually start to subconsciously do that less. In addition, you are pushing yourself to a state of
01:53:39.560
nutrient deprivation much sooner than was necessary to achieve a fat loss outcome.
01:53:45.900
So rather than trying to lose six pounds in two weeks, why don't I go with one to two pounds at most
01:53:53.660
and actually milk what I can out of that little tiny calorie increment before I decide,
01:53:59.820
okay, do I need to then add some more cardio to my regimen? Or do I want to decrease food by another
01:54:05.260
hundred calories? Or do I want to add metabolic enhancing pharmacology? You can actually make the
01:54:12.280
call at that point because you've exhausted the actual increment and you know you're not unnecessarily
01:54:17.680
depressing hormone production and also putting yourself into a hole of what is essentially a
01:54:25.360
malnourished state because if you push too hard and you go from let's just say you're eating 2800 calories
01:54:31.520
a day and you instantly drop to 1800, you will lose a ton of weight off the rip and you'll think oh this is
01:54:38.720
great and then very soon you will get to a point where it's like holy hell I am starving, this is not
01:54:43.840
sustainable. What am I doing? What do I do next? I plateaued now and where do I go from here?
01:54:48.760
It becomes easy to dig yourself into a hole if you're not careful about this titration down
01:54:53.520
essentially. So I typically recommend trying to milk what you can until weight loss has averaged out
01:54:59.500
at neutral for at minimum a few days but typically a week and then from there because as a natural you
01:55:05.880
are very susceptible to major aberrations and hormone suppression if you are going to deprive the hell out of
01:55:11.360
nutrients and especially if you're doing huge amounts of cardio concurrently because you think that's what
01:55:15.520
you need to be doing also don't put yourself in a hole on the energy expenditure side try and do what
01:55:21.840
you can in a titrating manner. I sometimes wonder if my low testosterone is in response to how much
01:55:29.700
fasting I used to do because I used to always do a check of testosterone I would do full blood work
01:55:36.160
before and after a fast so if I was doing a seven to ten day water only fast which I was doing once a
01:55:42.320
quarter the change in hormone levels after seven to ten days of nothing was profound so if my testosterone
01:55:49.360
started out at five to six hundred it would probably end at one to two hundred total T if my TSH was
01:55:59.120
two it would go to four maybe even higher maybe even six but free T3 and reverse T3 if free T3 was
01:56:10.320
two and a half to three and reverse T3 was 12 so the higher the free T3 and the lower the reverse T3 the
01:56:17.680
better thyroid function you have post fast that free T3 would go maybe from three down to one and a half
01:56:24.080
and the reverse T3 would go from 12 to 32 yeah not surprising yeah and so I just wonder if repeating
01:56:31.840
that cycle over and over and over again has maybe impacted endogenous production although interesting
01:56:38.320
my thyroid function looks stone-cold normal it's just that my T is very low yeah I would be interested
01:56:43.920
to see like what your gonadotropins did when you went back to normal dieting at that point and then how
01:56:50.320
you responded from there because if you could see like a trend in your testicular response too and
01:56:54.960
how your brain was shooting things out that'd be interesting what about things like carnitine
01:57:00.080
caffeine what role do these play in weight cutting not nearly as much as good diet choices so I would
01:57:07.600
love to get into the fat loss pharmacology momentarily there's a lot of diet hacks that we could take all
01:57:14.800
day talking about so I don't want to bore the audience but one thing I do want to mention that is
01:57:19.040
super impactful is protein ice cream I don't know if you've ever had this stuff but there's
01:57:23.840
this thing called a ninja creamy and it's basically a mixing device just like the blender yeah but this
01:57:30.080
one in particular is very popular lately because of the consistency of ice cream that it creates what's
01:57:37.760
it called ninja creamy like c-r-e-a-m-i so it's not the blender it's a device that's different from their
01:57:43.680
blender correct so this thing mixes what is already blended into an ice cream so you would put it in
01:57:50.400
the freezer blended and then you put it into this thing and it would turn it into an ice cream
01:57:54.560
consistency got it and what do you put in it how do you make it um well it depends what you want to
01:58:00.080
put in it because you could make this as healthy as you want which is essentially just like way isolate
01:58:05.200
plus some non calorie filled like sweetener if you want to risk it maybe some sugar-free
01:58:12.560
pudding mixture in there too like a chocolate or something and from there you could have something
01:58:17.040
that is like 300 calories if even and is as good tasting as horrible ice cream but hits you know like
01:58:26.160
a 60 gram protein hit with super high quality stuff minimal sugar content is like 80 as good as
01:58:34.800
something you would buy in a store almost like the consistency makes all the difference here because
01:58:38.560
it's like typically and this was how it worked when i was younger and i first tried all this stuff is
01:58:45.840
perhaps there was a similar device but at the time i was using a standard i think it was a i forget which
01:58:51.600
blender it was from costco but i tried a ninja a different one before another one i used to put in like
01:58:56.000
huge amounts of ice fruit you could do fruit too obviously and make it but basically the consistency i got
01:59:01.520
out of it was not that attractive so it was not like you could tell it wasn't ice cream you're kind
01:59:05.520
of eating like this sludgy healthy thing but this it's like you could make it near not identical but
01:59:12.880
pretty damn close i'm actually derailing our conversation to come back to it like that's how
01:59:16.560
significant it is so for people who are wanting that sweet tooth but if i make a protein shake
01:59:22.080
what i'm going to use is real simple i'm going to use almond milk or cashew milk so as my wife calls
01:59:28.080
them nut juice yeah like a whey protein i'll typically mix the unflavored pro mix yeah do
01:59:35.200
you know that brand no pro mix i think it's maybe i'm getting it wrong anyway it's unflavored way
01:59:40.080
high quality way but i like it and i'll go 25 grams of that with 25 grams of one of the other flavored
01:59:45.360
ones but that way it just cuts i still get 50 grams but half the flavor because i find them so sweet
01:59:50.720
and then frozen berries and that's it imagine that not drinking it but actually eating it and it takes
01:59:57.120
10 to 20 minutes to eat but the consistency is that of actual ice cream so i would blend that in
02:00:03.440
the blender and then put it in this ninja creamy thing and stick that in the freezer you would put
02:00:08.320
it in the blender and blend it and it would be in this thing that you would freeze overnight and
02:00:14.160
ideally you would have your wife or somebody mass blend multiple so you can just stick it in the thing
02:00:18.960
but anyway once you have these frozen ones you stick it in the creamy and then it mixes up a serving
02:00:22.720
of ice cream for you and from there you would have the same macros but it's infinitely more satiating
02:00:28.880
right because liquid doesn't satiate me very much and it's not just the speed of ingestion though too
02:00:34.000
that's part of it for sure but there's just some psychological component of eating something and one
02:00:39.440
of the things i can say too is low-hanging fruit for dieting and chopping many hundreds of calories off is
02:00:44.880
immediately anything you drink unless it's water if you can switch it to some sort of solidified format
02:00:52.240
you will be infinitely more satiated maybe not infinitely but like a significantly more satiated
02:00:57.040
so no juices no nothing like see if you can make that into a a slush of sorts or something that you
02:01:03.600
would wanna instead of that tequila i like to have i'm gonna make like tequila sticks like i want to
02:01:08.080
freeze oh dude but alcohol doesn't freeze this is the problem i can't make little tequila popsicles i know
02:01:13.840
some people who do like protein popsicles pre-workout popsicles they do the ice cream they
02:01:19.120
do like protein brownies like so much stuff that can be done when you get creative it's just you need
02:01:23.680
to have a significant other who's down to do it it's the only problem why do you need your significant
02:01:29.360
other if you like cooking and you like spending time on that stuff then perhaps that's fine for you
02:01:34.880
but like at least for me and for a lot of dudes out there it's like i don't know i'm missing
02:01:39.920
something here this isn't that time consuming right you're just blending this stuff up and you
02:01:43.520
put it in the freezer i'm more talking about some of the more creative stuff like the brownies and
02:01:47.680
stuff like that people might just call me lazy or far too optimizing i will not do anything
02:01:54.400
kitchen related if i could oh man i love cooking that's a blessing for you then you can get really
02:02:00.160
creative and actually enjoy the process for me i'm like i really hope i can throw it in a microwave
02:02:04.960
and cook it and it's still high quality food okay so let's talk about some of the fat loss from a copia
02:02:09.920
so i have friends that swear up and down by carnitine l-carnitine i think they inject it
02:02:15.200
so tell me about that l-carnitine is present in red meat and depending on your diet you may or may
02:02:22.880
not be deficient in it and it is something that can help incorporate free fatty acids into the
02:02:28.560
mitochondria and help you produce energy and it also is implicated in certain indirect processes like
02:02:34.800
ar content in the muscle which is some of the more fringe literature but it seems to in the presence
02:02:42.960
of sufficient anabolic stimulation actually increase the expression of what you can get out of your
02:02:49.360
testosterone input so this is the main reason why people i know use it and presumably why a lot of
02:02:54.480
people use it that you know too is it's often advertised as get more out of less androgen essentially
02:03:02.080
but does this work if you are getting sufficient carnitine in your diet do you need supra supra
02:03:07.920
physiologic doses in general if you're injecting 500 milligrams for example like you will be supra
02:03:14.960
so similar to creatine you can make the argument that endogenously or through your diet you maybe
02:03:20.800
get enough maybe you're not going to saturate muscle stores but i mean it's not analogous to creatine but it
02:03:26.080
seems to be at least in supplemental form and this is something you inject sub q daily
02:03:31.920
depending on the volume because it is depending where you get it could be 200 milligrams a milliliter
02:03:37.200
500 a milliliter and you can only put so much water-based sub cube before you have lumps so even
02:03:43.600
though it's more easily absorbed it's still not something you want to be injecting milliliters of
02:03:50.480
so are we back in the same problem of like where are people getting this stuff typically compounding
02:03:54.880
pharmacies or online or they're making it themselves because it's just an amino acid that you could just
02:03:59.440
buy anyways so homebrew sometimes homebrew how are they sterilizing the water and i'm not a campus
02:04:05.520
who's going to explain really how you would do it but it's the same process by which you would make
02:04:10.800
your underground steroids presumably i mean in other words this is a bad idea yeah maybe yeah this is an
02:04:15.360
awful unless you know what you're doing because some of them are like pretty intelligent but i still
02:04:20.320
wouldn't risk it even if i had the instruction manual personally so in general though there is
02:04:24.880
pharmaceutical not grade but like compounded versions that are made in an environment that's
02:04:30.800
been at least fact checked depending on the rigor of the pharmacy in question of course because you've
02:04:35.520
done deep dives into compounding which i recommend people check out i think we did an ama where we
02:04:40.800
covered the ins and outs of compounding and even with compounding pharmacies there have been enormous
02:04:46.640
breaches of good manufacturing processes and that results in contaminations of
02:04:53.360
legitimate fda approved molecules like corticosteroids that have led to literally
02:04:58.560
thousands of deaths so it's one thing when people are compounding things without good manufacturing
02:05:04.960
process that you'll take orally because the gut is a lot more forgiving but the moment you start
02:05:10.240
talking about things that are injectable and now you are injecting something in yourself that's dirty
02:05:15.520
that could be a huge compromise so i hope there are ways for people to vet that stuff
02:05:20.480
how effective is caffeine both in terms of its effect on appetite and potentially its effect on fat
02:05:28.000
oxidation i want to touch on carnitine quickly the reason people inject it is typically because the
02:05:34.160
oral format is only about 10 to 15 percent bioavailable so you have to take literally 10x the dose to achieve
02:05:41.840
the same yield outcome and then in addition to that when you ingest things like carnitine and choline there is
02:05:49.200
a potentially unfounded but still potentially concerning scenario where there is tmao conversion
02:05:57.280
so when you ingest a lot of carnitine like four plus grams to get your yield that is enough to
02:06:03.600
actually have some sort of effect that has shown to have some hopeful ar content up regulation which
02:06:09.680
is still like a fringe thing you're seeking that may not be ultimately founded you are using an amount that
02:06:15.680
is going to have some level of conversion that you could avoid by injecting so you are averting the
02:06:22.400
need to use as high of a dose and in addition to that you are potentially avoiding some level of risk
02:06:29.120
from gut related circumstance some people use allicin with it to kind of like circumvent and try and
02:06:34.960
prevent tmao conversion it's from garlic and it seems to attenuate tmao conversion in the gut but it's also
02:06:41.280
like a fringe application with like a hopeful outcome that i guess you can measure in serum
02:06:46.720
your tmao before and after allicin versus not and see if there's a difference are there any clinical
02:06:51.280
trials that demonstrate any efficacy of injectable or oral l-carnitine with carnitine the results are
02:06:57.760
mixed some of it looks promising and then some of it doesn't so this is one of those things where
02:07:03.360
you largely go by anecdotes and with it being a natural amino acid a lot of people that use it
02:07:08.880
it depends on their baseline circumstance too the deficient will obviously get more exactly like
02:07:14.080
you could sort of see a scenario where somebody's like a vegan and then you might see well maybe the
02:07:20.160
risk is worth the payoff but if you're an omnivore who happens to eat red meat i don't know maybe it's
02:07:26.160
less so i'm sure if you saw the data you would not be convinced that it's worth trying so i'll just
02:07:30.640
put that out there for people who watch your stuff i don't think that they would blindly want to inject
02:07:35.440
this so the reason people find it very attractive is because it works through a different vector
02:07:41.120
people anecdotally have seen muscle growth outcomes on the same dose of anabolics or less or so
02:07:47.680
and a grow leaner when they use it so it's not like there's literature to show when you're on
02:07:52.400
testosterone plus carnitine you get better results than just test but that's what people claim and seems
02:07:58.400
to be at least somewhat reproduced anecdotally but that's speculative i would not hang my head on that
02:08:03.920
and be like i recommend for sure you take this so putting that out there i don't think it's a
02:08:08.320
potent fat burner by any means which is like the subsection we're kind of talking about as far as
02:08:12.480
caffeine super reliable one of the best things you could do you know where the data lies for upper
02:08:18.160
tolerability and safety i think the fda even has like a threshold amount that they say you're good to
02:08:22.880
take it's like 400 which is pretty significant and yeah you can get some level of increased energy
02:08:29.040
expenditure from that but largely the benefit from the stimulant category i would say comes from
02:08:36.720
the increased energy you have even as you go deeper into a deficit as well so as you enter into
02:08:43.200
nutrient deprivation territory it becomes a lot harder to even move subconsciously let alone actually
02:08:49.680
fuel your everyday activities so i'm not to say you should become a caffeine addict to support your
02:08:54.160
deficit that's not necessarily sustainable but if you were going to use something to help
02:08:59.760
attenuate an energy deficit or one day where you need a bump caffeine is certainly a reliable way to
02:09:07.200
do it that increases metabolic output but also reliably increases performance in the gym and has
02:09:14.080
appetite suppressing qualities and has safety data simultaneously so i would pretty blindly recommend
02:09:20.480
caffeine for most people short of like special circumstances you mentioned yo him being earlier
02:09:27.040
say more about that so that is a alpha 2 adrenergic antagonist and when it comes to some of these like
02:09:33.840
adrenergic type receptors it gets kind of confusing even though it's an antagonist of the alpha 2 receptors
02:09:40.880
it will have stimulatory effects but contradictory to what you'd expect from a stimulant it's not
02:09:47.360
vasoconstrictive the same way you might get from a amphetamine or like essentially any other stimulant
02:09:53.600
that works well so this stuff raises adrenaline signaling very significantly and there is thought
02:10:00.160
that it could liberate free fatty acids via the adrenergic signaling that you could then take advantage of
02:10:06.720
during exercise now is the energy expending component of it worth hanging your hat on i would say no
02:10:15.680
but the adrenaline inducing component is substantial enough that some people really really enjoy the
02:10:22.720
use of it in their training and get a uptick in energy that is markedly different than through a
02:10:30.560
adenosine receptor antagonism which is which is caffeine yeah so like it feels much more racy
02:10:36.400
and aggressive than caffeine how does it compare to like ephedrine ephedrine i believe is a beta
02:10:43.360
two receptor agonist off the top of my head i could be wrong on that but it is less euphoric i would say
02:10:49.360
and more like adrenaline spiking so you feel more like almost borderline anxious to a degree where you
02:10:57.520
have a sense of urgency how long does it last johanbein half-life can't recall off the top of my
02:11:03.760
head but it's relatively short is it the type of thing that people take for the workout when they're
02:11:07.840
a calorie deficit typically you would take it before cardio or before training is the typical
02:11:14.320
application but interestingly enough it's also used as an aphrodisiac and can enhance erections
02:11:21.440
which is weird you wouldn't expect that from a stimulant and also like that doesn't seem like the
02:11:25.680
right mix of things to be super anxious and irritable sure yeah but that's one of the things
02:11:32.000
where it's like is this a drug for you because if you happen to get an uptick in performance in
02:11:36.720
exercise performance and then also you get some sort of uptick in libido and or enhanced bedroom
02:11:44.240
performance later in the day could be attractive i would typically reserve it for a deficit whereby you
02:11:53.120
have tried all standard low-hanging fruit options and you're kind of okay now i need to actually boost my
02:12:00.880
energy in some way that is not like i'm at my wits end for i can't do more cardio or reduce my intake
02:12:08.000
of calories anymore without it being overwhelming or i'm just in like a very deprived energetic state
02:12:13.840
or i got low sleep and i need to acutely modulate it so i don't use it i wouldn't use as much as
02:12:19.040
caffeine caffeine i would very easily recommend daily use in a diet i think this is something that's more
02:12:25.200
use case specific and not as reliable one of the clinical scenarios i see a lot of that i think
02:12:32.320
plays a significant role in the state of over nutrition again i've talked about this when i
02:12:37.440
look at somebody i want to know these three things really quickly right are you overnourished or
02:12:41.360
undernourished or adequately nourished are you adequately muscled or under muscled are you
02:12:45.920
metabolically healthy or not and depending on where you fall in that matrix you have to decide whether
02:12:51.440
their calories need to stay the same up or go down now one of the scenarios that is i think
02:12:58.000
most clinically vexing is the person who is overnourished typically metabolically unhealthy
02:13:04.400
typically under muscled so that's a pretty common phenotype you're a little too fat you don't have
02:13:09.440
enough muscle and you're not metabolically healthy and a big part of the driver is basically the
02:13:15.920
hypercortisolemia that accompanies sympathetic overdrive so an individual that is under so much
02:13:22.960
stress chronic stress that you basically can't stop the glucocorticoids from chronically being
02:13:32.800
catabolic to lean tissue and anabolic to fat tissue and when you think about all the other endocrine
02:13:40.000
scenarios like we have ways to kind of manipulate them this one we don't really there are certain
02:13:45.760
things we can do you can use ashwagandha you can use phosphatidylserine they certainly help with
02:13:51.040
sleep in that setting but do you know anything or do you have any insights into ways to manipulate
02:13:56.960
that person's physiology in addition to pulling the big three important levers around nutrition sleep
02:14:04.400
and obviously exercise yeah and by the way the alpha-2 receptor antagonists yohimbine and alpha-yohimbine
02:14:11.680
which is a bit better of a drug in my opinion are definitely not the drugs you want to take if
02:14:15.520
you're in the hypercortisolemia that's right that's what made me think of it is when you brought them
02:14:19.360
up i'm like well that's actually producing a phenotype that a lot of people are in chronically
02:14:23.760
yeah some people the use case again it's not like it's indicated or anything but some people get a
02:14:30.880
significantly better appetite suppression effect out of those particular drugs too than something else
02:14:36.080
that might be where you would look but anyway that aside as far as actual anti-catabolic action the
02:14:43.200
most potent thing i'm aware of is actually anabolics there are certain ones that are
02:14:48.560
more potent at antagonizing the glucocorticoid receptor and actually compete with glucocorticoids
02:14:54.080
for binding and that's where they get their anti-catabolic action and deficit so something
02:14:58.560
like oxandrolone not that you can get it now which we could talk about but that in like burn victims
02:15:04.400
it is literally indicated for antagonizing the heightened cortisol glucocorticoid response that
02:15:09.920
you get from being in that state so it is one of the most potent anti-catabolic drugs what happened
02:15:15.120
there oxandrolone was also scheduled just banned altogether what's the status of it it's my
02:15:21.040
understanding and i may be not entirely correct but it was fda approved for many indications and then
02:15:29.680
basically the fda determined based on and this seemed like kind of a nonsense thing but uh meeting in the
02:15:38.160
80s where they determined that anabolics in particular anavar by extension had no efficacy
02:15:45.680
anymore essentially and for whatever reason they determined that that decision back then if you go
02:15:53.040
far back enough you can find studies where they're like anabolic steroids aren't performance enhancing
02:15:56.880
it's like obviously nonsense but at that time that was what the literature available showed and it
02:16:02.320
almost seems like they're leaning on some of that in order to justify pulling it we don't think it is
02:16:07.440
useful for all of these approvals anymore and then there's pressure from that for all of these
02:16:13.440
companies that have generic approved versions of it to subsequently pull it as well i'm sorry so the fda
02:16:20.800
pulls anavar which is the branded version sorry yeah so anavar is made by a pharmaceutical company
02:16:26.960
and i'm referring to oxandrolone the chemical not anavar understood but they're speaking to the
02:16:32.880
molecule yeah not the branded drug yeah my apologies sometimes it's easy to conflate what the laymen
02:16:39.040
speak for these anabolics is too but i'm just saying then it doesn't really matter who makes
02:16:43.440
it isn't this exactly directed towards not just the company that makes anavar but even a compounding
02:16:48.000
pharmacy they would make oxandrolone yeah so they are saying that there is now no approved use for
02:16:53.120
oxandrolone in totality so if you are a pharma company who has a generic version of it or you're a
02:16:59.920
compounding pharmacy that makes it there is no approved use for it so you presumably can't
02:17:05.440
justify the prescription of it as a doctor unless you're can somehow lean on a i guess it's not even
02:17:10.640
off label because there's no well that's what i was about to say so is the implication that if there's
02:17:14.320
a patient in a burn unit and a physician there says we've been using oxandrolone for years and it's
02:17:21.440
got great results can they override that for a exemption i feel like you would be able to tell
02:17:28.400
me hopefully i'm not sure man i would think yes i would just imagine there's higher risk to actually
02:17:35.760
prove that it was a necessity than it used to be and then where do you get that filled some pharmacy
02:17:40.880
that is a bit of a cowboy pharmacy that's making it i'm not really sure so what i do know is compounding
02:17:47.360
pharmacies are making it as of now still and the pharma companies that had generic versions of it
02:17:53.600
have pulled voluntarily their own approvals essentially so these companies that had like
02:17:59.680
oxandrin which was what i know to be what used to be anivar which was sold multiple times and
02:18:05.920
oxandrolone is taken sl it's taken under the tongue right if you get a trochi from a compounding
02:18:12.160
pharmacy you could get a sublingual format of it but it's typically a pressed tablet that you just
02:18:17.920
pop and you would take it twice a day orally yeah isn't that kind of hepatotoxic a little bit but it's
02:18:24.000
one of the least hepatotoxic 17 alpha alkylated anabolics there is so if you look at the pharmacology
02:18:30.160
of it it is metabolized by the kidneys proportionally more than any oral agent and that creates a superior
02:18:40.000
hepatotoxic outcome where it's not nothing but it's lesser than oxymethylone anadrol or like you
02:18:47.040
know winstrol or some of these other ones or stenozolol yeah stenozolol is injected right that's
02:18:52.560
typically taken orally but it's also injected in water base but almost no one does that bodybuilders do
02:18:59.600
but it leads to infections very often so they often don't do it now to me listening to this all roads
02:19:05.760
point back to nothing seems to matter more than what you eat when it comes to body composition
02:19:10.800
what you eat and how you exercise oh for sure like all this other stuff is like a rounding i mean
02:19:15.680
it's 90 exercise diet and testosterone and it's 10 all of the other stuff yeah and i think a good
02:19:24.320
note to make because the last time we spoke we had talked about the development of pharmacology and
02:19:30.960
what is leading to the change in physiques as of recent and i said in order it was like drugs and
02:19:37.600
then diet and then training i don't even remember what the order was the last two it almost doesn't
02:19:43.120
matter when drugs are like that important for achieving the outcome on a mr olympia stage all
02:19:48.160
but and this is the caveat that i definitely want to make clear here if i wasn't in the first one
02:19:52.320
just in case what you just said that 90 of it is this you do not achieve even the outcomes from
02:19:58.880
anabolics without the support of a great infrastructure of diet and training and sleep
02:20:05.280
so as much as it could be a band-aid for shitty all those things you will achieve a fraction of
02:20:10.960
the results even on anabolics if those are not in check i've even done it myself as much as i don't
02:20:16.240
want to admit but i've talked about this publicly when i was younger i thought what would it look like
02:20:21.360
if i just did uh like i've seen hyper responder bodybuilders do fluff workouts and get crazy results
02:20:27.600
being the guy who wants to experiment with everything maybe i'm just working too hard
02:20:31.440
maybe i'll try like the fluff phil heath workout i saw or something on youtube turns out it doesn't
02:20:36.320
work for me at all i basically wasted a full cycle of exposure to these compounds to get almost nothing
02:20:42.640
out of it because my training was kind of half-assed so having that baseline regardless if you're natural
02:20:48.880
or enhanced it is the fuel to actually support the recovery that may be at an enhanced level with
02:20:56.240
anabolics but like it still doesn't exist without these things has someone done the study of
02:21:03.120
testosterone replacement therapy in a non-active individual who doesn't change any behavior and how
02:21:10.480
minimal the changes are yeah so the boston study which is like the standard graded dose response
02:21:18.960
study that everyone's familiar with he had two different studies that were using 600 milligrams
02:21:24.240
of testosterone one of them was graded dose response 600 a week or every two weeks a week
02:21:29.520
holy cow kind of 6x physiologic dose essentially yeah the other study that i think was done in the
02:21:36.080
90s was doing 600 milligrams of testosterone versus placebo in a non-training training and then also on
02:21:45.840
the testosterone non-training training individual two by two yeah yeah and what they found was that the
02:21:53.200
obviously the 600 group who trained got the best outcome but the group that didn't train and took 600
02:21:58.480
tests still had better lean body mass outcomes than the training placebo group yeah which kind of spits in
02:22:05.520
the face of what i just said a little bit although that's 600 milligrams yeah so you almost need to
02:22:10.960
see that on 100 you also have to draw it out over the span of a training career like you're not going
02:22:16.480
to sustain perpetual muscle growth and some of that is ultimately when you take steroids for the first time
02:22:23.520
there is a temporary increase in lean body mass metrics that are essentially and you could probably
02:22:29.920
speak this better than me unquantifiable by standard metrics of measurement of body composition because
02:22:37.040
ultimately the way these work is not just through the production of muscle protein synthesis and contractile tissue
02:22:44.400
it's also like the increased intracellular water that you would not hold otherwise and the increased blood
02:22:50.400
volume and increase this these are things that although they're not contractile they are still making up your
02:22:57.440
muscle which is largely water so even though they do try to account for like total body water that is
02:23:04.160
not muscle based you are still some confounding level of the drugs actually facilitate this as the desired
02:23:12.880
outcome so there's going to be some of that in the outcome regardless but i think it's unquestionable
02:23:21.120
that anabolics even if you're not training will produce a level of muscle that is higher than if
02:23:27.680
you had no hormones like that's definitely an outcome to wrap up any influencers online you're
02:23:35.120
particularly excited about as far as like just the amount of buffoonery that's going on anyone that
02:23:42.160
particularly has you excited i mean one of the things you're known for is debunking the charlatans you've
02:23:48.160
done some legendary work in this which will link to some of your best videos on this is there anybody
02:23:53.200
you're looking at now just sort of shaking your head at like how is this person fooling so many
02:23:58.080
people we've talked about him briefly gary brecca he has a lot of good information don't get me wrong
02:24:03.920
i don't want to turn this into a shitting on him parade necessarily but the guy very heavily emphasizes
02:24:12.800
the importance of getting gene testing for a limited amount of snips that are ultimately very
02:24:20.640
common to find in general population and then making wild extrapolated claims from that that assert all
02:24:28.080
of your ailments and problems could be attributed to this and then he has good information that's general
02:24:33.360
about lifestyle training sleep hygiene but then he'll sprinkle in these like aggressive claims about
02:24:39.920
methylation if you have your homozygous for c677t mthfr which i am and a lot of people are almost
02:24:47.040
everybody yeah then you need to be taking this exact blend of methylated b vitamins and he speaks very
02:24:54.560
articulately eloquently confidently concisely and it very much gives the impression that this guy
02:25:02.320
knows something you don't know and you should be following his advice because he ultimately is the one
02:25:06.320
who transformed dana white's physique too and dana white speaks very highly of him and i don't know
02:25:14.080
man like some of the products he sells it's like he has a 140 000 red light bed does that improve
02:25:20.000
methylation i don't know i have no idea to be honest i would assume probably doesn't do a lot of anything
02:25:27.440
but i haven't even looked into it to see because it just never even occurred to me as something worth
02:25:32.560
looking into but it seems a bit expensive you know objectively borderline you're in a low-end exotic
02:25:39.760
car territory essentially for a fucking bed that emits light on my face so i'm a bit skeptical and then
02:25:46.160
he has other stuff but in particular his gene testing how much does the testing cost i think it's like 600
02:25:53.520
bucks so 600 for a gene test yeah so it's like assessing for example if i got a 23 and me and i
02:26:02.160
had my data i could submit it to rhonda patrick or somebody who has one of these like automated reports
02:26:07.120
and get something as comprehensive or more so with no suggestions to buy stuff after that either just
02:26:13.840
like straight up here's the interpretation based on everything we know about these snips and it would
02:26:18.720
tell me if i had methylation impairments we do all of those tests as part of a standard blood panel and
02:26:23.440
it's basically free yeah yeah i've known that mth of our stuff is also in your uh yeah it doesn't cost
02:26:28.880
anything so i mean 600 seems a lot given that you can do a whole genome sequence now three billion
02:26:36.480
base pair we're not talking snips whole genome sequence for 300 today damn that's crazy i don't know
02:26:44.080
man but then you get his you know interpretation of it which is it almost feels like he's hoping you
02:26:49.280
have one of the most aggressive methylation impairments so he could point to it and say
02:26:54.240
here's why you feel this way like that feels like what i'm gathering from the content or oh you clearly
02:27:00.320
are a worrier because of your comt polymorphism here this is why you are so concerned about little
02:27:07.440
problems that you shouldn't be ruminating over all you need is some sammy or whatever i feel like
02:27:13.280
even if you are right you got a needle in a haystack because there's so much that goes into
02:27:18.480
genetics that is beyond these maybe common snips that have some impact like for example if i'm the
02:27:24.480
most methylation impaired sure i'll look at betaine or whatever to lower my homocysteine like totally
02:27:31.360
reasonable but like don't assert it's the root of my everything that's wrong with me or i don't know
02:27:37.280
like he highlights it as it's just like comes across a little bit disingenuous to me and i really do
02:27:42.400
wonder how much of it is him perhaps deluding himself because he speaks so confidently it's
02:27:49.120
hard to believe he's this good of an actor or just genuinely doesn't know which i think is unlikely but
02:27:55.280
i mean like he goes on the biggest podcast in the world and spits complete misinformation says that t4
02:28:00.240
is methylated in the gut to t3 and like all this what yeah so if you have a gene mutation or if your
02:28:05.840
mthfr is messed up you will not convert t4 to t3 and that's why you might have hypothyroidism
02:28:12.640
that was an assertion made recently on joe's podcast which is pretty wild to me because joe is
02:28:18.480
actually hypothyroid and has been for a long time so you're basically appealing to
02:28:24.000
some like actual medical condition he has saying you have the answer and it's your like cheek swab
02:28:28.880
thing and it's like i'm highly doubtful that's the case and i'm nearly certain that methylation is
02:28:33.760
not the thing that converts t4 to t3 it absolutely most certainly is not it's a series of enzymes
02:28:39.040
called diodinases that make those conversions and to my knowledge has nothing to do with your mthfr gene
02:28:45.120
yeah chris masterjohn had a really good video recently that kind of like summarized it all i
02:28:49.680
would recommend people check out his stuff if you want to know anything about methylation you've had
02:28:52.800
on the podcast super intensive and great podcast by the way we'll link to chris's discussion on that
02:28:59.520
anybody else out there that's got you excited i don't know i guess brian johnson's an interesting
02:29:04.880
too dude we talked about briefly johnson the liver king other brian johnson the vegan king i don't
02:29:11.680
know he doesn't have a nickname brian johnson's in the world yeah and shockingly as prolific as each
02:29:17.440
other just in their own way so yeah this guy is the total antithesis of that guy's diet model he's like
02:29:23.360
eating sludge vegan shit on camera every day and saying it's proven by data to be the answer to
02:29:29.280
longevity i don't know he's done the folistatin thing he's done tons of stuff he's on telomere
02:29:34.720
lengthening peptides he's on thymus regeneration enhancing peptides ones that are all banned now based
02:29:42.000
on the thing or at least category two i don't think i've ever seen somebody on more stuff than him like
02:29:47.280
his protocol is endless and i'm like how do you control for anything at this point the other day he added
02:29:52.880
in oral minoxidil at two and a half milligrams which is super outdated antihypertensive that
02:29:58.480
causes edema is he doing it for hair growth yeah but it's like okay you've added that in which could
02:30:05.040
affect myriads of things that are also affected by the 77 different things you're on right now like
02:30:11.760
obviously hair growth is a pretty easy metric to count but when you're counting health metrics on
02:30:16.640
organ function and stuff i just don't really get how he's controlling for everything granted no one
02:30:21.120
else is doing it so it's interesting but i watch with skepticism about what is going to come of it
02:30:26.400
if it's going to become this monetary incentivized hype train or if he's just going to produce the
02:30:32.080
data some like noble billionaire dude who's just doing it for the good of longevity community or what
02:30:37.280
but i don't know he's interesting what's up with mr v shred i don't know because i have my youtube
02:30:43.840
premium so i don't see him yeah you gotta get on that dude did you do it last night i didn't do it
02:30:49.200
last night i'm gonna do it get on that what does v shred do he it's like i don't even know where to
02:30:56.080
start with the worst things he's done the business model is despite having seen the commercials i still
02:31:01.760
don't actually know what to do i have that skip button that i use in general i think his go-to's
02:31:07.680
are here's your body type quiz and you tell me if you're like an ecto mezzo or endomorph i mean
02:31:13.680
remember the types at this point but and from there i will tell you the diet that you need
02:31:18.400
to like actually get lean because you've been given misinformation by everyone else this whole
02:31:22.320
time and then you end up with his program if you're an ectomorph you're already lean yeah so
02:31:28.240
if you're an ectomorph you can do whatever you want is that the takeaway i don't know i've heard
02:31:33.120
his programs are pretty cookie cutter and it doesn't surprise me because he's clearly a hammer you
02:31:37.280
at scale i'll just recruit as many people even to the detriment of my credibility kind of guy
02:31:42.320
so i don't think he gives a fuck what happens but also very old school marketing but like harvard
02:31:48.560
has discovered this secret ingredient that they've been keeping from you and it's the secret to fat
02:31:53.280
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
02:31:58.800
hyping this thing up and you've invested so much time to find out what it is you're thinking there's
02:32:02.720
no way i'm gonna buy this shit you just want to find out what he's gonna say at this point it turns
02:32:06.000
out it's like capsaicin which is from like peppers or something and it makes you feel a bit hot and it's
02:32:11.280
like okay so i waited for you to drop the capsaicin on me now what and then he's selling me a fat burner
02:32:16.560
that has some negligible amount of caffeine and capsaicin like four other things which is like
02:32:23.200
pretty typical old school marketing that is not that great certainly not ethical and then he'll sell
02:32:29.280
it for like 130 even though it's worth four dollars to manufacture the bottle costs more than the
02:32:34.240
ingredients like that's how bad it is but he's giving us a discount because we made it through the
02:32:40.160
video and you know we're clear so instead of 140 you'll get it for 99.99 yeah yeah but on
02:32:44.560
subscription on subscription you don't run out of course yeah of course yeah he's doing as a service
02:32:50.000
one of the worst ones i've seen though was him pretending to be on the joe rogan podcast i did see
02:32:54.320
that little commercial that was unbelievable yeah i don't know if josey and i haven't sent it to him
02:32:58.640
but like dude it was almost ingenious level unethical like to actually think you know without
02:33:06.320
even having to say it that's what people are thinking oh this guy was on the podcast he's
02:33:10.640
probably a trusted authority on x whatever he's talking about joe must trust him because he's
02:33:15.360
asking about what he should do with his diet he's just sitting there like confidently i know it's
02:33:19.920
complicated but this is how fat loss works let me tell you the secret you just need to take my body
02:33:26.640
fat quiz joe so go to vshred.com slash whatever and it's like surely people fall for it you see
02:33:34.720
the ad over and over again so it's like that means it's working because he's dumping the ad dollars
02:33:38.880
into it so i don't know i feel like that guy needs to change his name and get plastic surgery at this
02:33:43.760
point to avoid the damage he's done to his credibility from people in the industry who know
02:33:49.280
who he is and it's just like an at scale hammer as many people as i can with ads kind of model
02:33:55.040
which it was interesting that you served up him so much well it's funny i haven't even seen an ad
02:34:02.080
for him in months there was a period when i was getting them non-stop i wonder if there's a way to
02:34:07.520
like selectively exclude certain demographics or something because surely knowing that you said he's
02:34:15.200
a huckster and you see his ads all the time and you were starting to say some stuff about him publicly
02:34:20.560
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
02:34:24.960
that's interesting yeah well my friend this was interesting uh the biggest takeaway for me here is
02:34:30.880
i need to get one of these ninja creamy things i'm really curious to see if i can up my protein shake
02:34:36.720
into ice cream game so let's order one of those things right now yeah i'm down let's go get you
02:34:42.080
youtube premium perfect yeah all right thanks man thanks for having me thank you for listening
02:34:46.960
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