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

00:00:00.000 Hey, everyone. Welcome to The Drive Podcast. I'm your host, Peter Atiyah. This podcast,

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00:01:04.300 My returning guest this week is Derek from More Plates, More Dates. Derek was a guest back on

00:01:10.180 episode number 274, which aired in October of 2023. In that episode, we didn't cover nearly as much as

00:01:17.720 I would have liked, so I wanted to have Derek back for round two. In this conversation, we continue where

00:01:23.180 we left off in our first discussion. We talk about a number of exogenous molecules that impact

00:01:29.500 both male and female health, including testosterone, DHT, DHEA, progesterone, clomid, HCG, and various

00:01:38.980 peptides. And we also talk about some updates from the FDA since our last conversation that impact the

00:01:45.660 use of peptides. We also touch on myostatin, folistatin, and more. We cover various ways that

00:01:52.260 bodybuilders will lose fat and weight while maintaining muscle, including the various weight

00:01:57.240 loss drugs that are available. As a reminder, Derek is a fitness educator and entrepreneur

00:02:01.980 behind the More Plates, More Dates YouTube channel, podcast, and companion website. So without further

00:02:08.140 delay, please enjoy my conversation with Derek from More Plates, More Dates.

00:02:17.440 Derek, good to see you again.

00:02:18.800 Thanks for having me again, Peter. I appreciate it.

00:02:21.620 Yeah. So last time we spoke, we covered a lot of ground and yet somehow at the end of it,

00:02:26.480 we felt like there was still a lot to talk about. So hence we're back. And I'm going to do something

00:02:30.820 unusual, which is I'm just going to tell you, Hey, what do you want to talk about as opposed to

00:02:34.820 driving down my agenda? I have a bunch of things that I want to talk about, but curious as to where

00:02:38.600 you think we should pick things up.

00:02:40.520 Yeah. I think that a lot of stuff we covered at a surface level,

00:02:44.500 and maybe there might be some unanswered questions or ambiguity on some specifics when it comes to,

00:02:50.520 am I a good candidate for hormone replacement? How would I assess that? Should I be worried before

00:02:56.540 I get on it? What kind of things should I look for? I feel like getting clear on that might be

00:03:01.300 worthwhile because a lot of people are kind of in that boat where they don't know who to trust.

00:03:06.140 They don't know who to listen to. And I know even yourself, you're kind of like teetering on the

00:03:09.720 thought of maybe exploring it. So I feel like even seeing what your thought process is going

00:03:14.100 into evaluating, is it viable for you? Would be super valuable.

00:03:18.040 Yeah. So let's maybe back up a little bit and give folks a quick primer on the topic.

00:03:23.360 So let's just start by just talking about testosterone. I don't know if it's just that

00:03:28.720 I'm more attentive to it or there's truly been an increase in marketing efforts, but it really seems

00:03:34.880 like the last decade and presumably it's also just the explosion of social media and more channels

00:03:40.780 through which this information comes at you. But clearly there's been a lot more attention

00:03:44.480 brought forth to this idea. And it's very interesting because there's historically been

00:03:50.560 kind of a negative connotation associated with testosterone, natural hormone. We can talk all

00:03:56.160 about that, but of course its role as a drug of abuse in sports has sort of tarnished it in a way

00:04:02.300 that we don't see on the female side. So when we talk about hormone replacement for women with 0.99

00:04:07.840 estrogen and progesterone, that doesn't come with the same performance enhancing benefits.

00:04:13.260 Which is odd, eh? It's viewed as such a taboo thing, even though at the end of the day,

00:04:17.060 it is just a natural hormone that you produce.

00:04:20.140 Right. And so it's interesting, of course, that estrogen and progesterone are not scheduled

00:04:24.260 drugs. They're hormones. You prescribe them without any limitation. They're unscheduled by the DEA.

00:04:30.380 Conversely, testosterone is scheduled and much more highly regulated. And again,

00:04:34.460 the suggestion here is that there's potential for abuse that we presumably don't see with estrogen

00:04:39.240 and progesterone. That's neither here nor there. It just is what it is. So maybe let's just talk

00:04:43.800 really briefly about testosterone, androgen receptors, how they work, the role of DHT, and what

00:04:50.940 this does for muscle protein synthesis. Maybe just a kind of quick background on that.

00:04:53.920 Yeah. So in general, most people are aware of testosterone as the primary masculine hormone,

00:05:01.400 but in reality, it's produced in significant quantities in both genders, just proportionally

00:05:07.260 more so in men to the magnitude of 10X that of females, I believe. And also both men and women

00:05:14.120 produce estradiol and DHT as well. They just have differing proportions and binding proteins and whatnot.

00:05:19.800 But at the end of the day, the action in the body is the exact same. It still binds to the androgen

00:05:25.040 receptor, induces gene expression, and causes muscle protein synthesis and other anabolic actions

00:05:30.600 in bone, psychoactive effects in the brain, etc. And just the magnitude to which it happens

00:05:36.180 differs between sexes. And it also is what essentially determines how you sexually mature

00:05:44.140 and differentiate as you enter adolescence. So you could realistically manually manipulate

00:05:49.240 it too. And you see this in sport, doping scenarios, bodybuilding males, you see it all the time.

00:05:55.060 So ultimately, this is the primary androgen that dictates muscle growth and anabolic activity in

00:06:01.980 tissues. And the metabolites of it regulate a bunch of other things in the body, which we could get

00:06:09.120 into. But to keep it like high level simple, it is the main primary androgen that men and women alike

00:06:16.320 rely on just that differing amount. I can't remember if you and I talked about it on our

00:06:20.000 previous podcast. I know it's been discussed on the podcast. We'll link to it in the show notes where I

00:06:24.180 go into great detail mechanistically about what happens when testosterone binds to the androgen receptor

00:06:30.080 and how that gets into the nucleus and how that impacts gene transcription into translation for

00:06:35.180 protein. What's interesting, of course, is that you did mention DHT. DHT has a significantly higher

00:06:41.280 affinity for the androgen receptor. Anything else you want to say about the role of DHT versus

00:06:46.920 testosterone? And we can just talk about it in one gender. We don't have to necessarily break it down. 0.99

00:06:51.780 Yeah. So the spectrum of, I said androgen, I didn't really elaborate what that even means.

00:06:58.480 As far as I know, the definition is essentially to be male or to make male or something related to

00:07:05.660 masculine characteristics ultimately is kind of what you derive from androgens. And the further 0.93

00:07:09.680 on the spectrum of androgenicity it goes, the more masculine and viralizing potentially in women

00:07:17.280 it could be. So DHT is that hormone essentially that drives this pathway to the extreme and is what is

00:07:25.760 responsible alongside testosterone for maximal sexual differentiation maturation in adolescence like

00:07:33.700 I mentioned. But you see mutations in the gene that encodes for 5-alpha reductase, which is the enzyme

00:07:39.400 that makes DHT. You'll note that certain pseudo hermaphrodites who don't have DHT will end up lesser 0.99

00:07:46.660 developed in the masculine spectrum than normal functioning human with full DHT production. So this is

00:07:52.820 kind of like an example of the spectrum of on one side, you have males producing 10X the testosterone

00:07:58.660 and more DHT subsequent to that. And then females much more estrogen proportionally to males. Well,

00:08:06.220 somewhat depending on where they're at in their cycle and whatnot. And then 10X lower the testosterone

00:08:12.040 and also much less DHT. And this ratio of androgens to estrogen essentially is what dictates,

00:08:18.380 are you going to have male characteristics or female characteristics? And how much are those

00:08:23.820 characteristics going to get exaggerated? Because even if you're a full grown female, 1.00

00:08:28.420 if you expose yourself manually to these hormones, you could very much push yourself in that direction.

00:08:33.940 So DHT, a lot of people know about it for its responsibility and what it does for hair loss,

00:08:39.860 the common side effects associated with it. But it is an important hormone that does regulate

00:08:46.880 how masculine you become as you grow up. So I think that's the best way to put it.

00:08:52.960 And there's a critical window of exposure too. So embryologically, obviously exposure to

00:08:58.720 testosterone and DHT have an enormous impact on sexual differentiation later in life. I'll give you

00:09:04.640 an example. I have a patient, female patient who's on testosterone and she accidentally for a period of

00:09:12.480 about a month, didn't read the directions correctly and was taking 10X the dose.

00:09:17.940 And that's not that hard to mess up. It's very easy to do. This is something you have to be very

00:09:22.800 careful with because the doses are so, so small. And there's no FDA approved women's testosterone as

00:09:29.540 well. Right. You could have it compounded in theory at a lower concentration, but regardless,

00:09:34.180 she for about a month ended up taking 10X the dose, which means she was taking a male physiologic

00:09:39.860 dose of testosterone. The symptoms immediately said, there's something going wrong here. The first

00:09:46.680 symptom interesting that she noted, I would have expected hair growth to be the biggest issue. It was

00:09:52.060 clitoral enlargement within just a period of a month. The good news is completely reversible once 0.87

00:09:57.700 the dose was restored to the 10th that it should have been. I don't really follow bodybuilding

00:10:03.220 closely enough, but I assume that female bodybuilders are routinely using doses of that nature. 1.00

00:10:09.320 Yeah, they are depending on their guidance, somewhat or very aware of the masculinizing

00:10:17.600 potential of what they're using. And some will avoid testosterone entirely because of that,

00:10:22.500 because it is essentially equal anabolic as it is androgenic. So it begs the question,

00:10:28.140 why would you be using testosterone as a female? If you're trying to achieve super physiologic muscle 1.00

00:10:33.160 growth, you kind of know in order to push it to that extent, you're probably going to end up in male 0.92

00:10:38.300 characteristic territory. So oftentimes they will defer to compounds like oxandrolone, which is

00:10:45.440 anivar. They'll use things like primabolin sometimes, metenolone.

00:10:51.060 So meaning much more anabolic, much less androgenic.

00:10:54.700 Yeah. So these are synthetic compounds that have been manipulated to be more tissue selective,

00:11:00.140 as in more anabolic activity relative to the male viralizing component. Unfortunately,

00:11:06.120 you can't segregate the two entirely, but they do what they can. And the best thing they can do is

00:11:12.200 keep an eye on the side effects as they manifest in very, very real time, keeping a close eye on it.

00:11:21.140 I know some women who even have a decibel voice recorder and they will monitor if their tone is 1.00

00:11:27.000 getting lower or not. Is that potentially an irreversible change if voice is changing?

00:11:33.180 Yeah. So you have to be super careful, especially even in TRT. If you were going to do TRT as a

00:11:38.640 female, a lot of the clinics nowadays will advertise and market testosterone in a way that is 0.95

00:11:46.400 highlighting how great it is for libido, quality of life, glucose management, muscle growth.

00:11:53.320 Like there's a lot of things that sound attractive about it that are an easy sell to a female who 1.00

00:11:57.680 may be asexual and like perimenopause or something. And I've seen standards being promoted as cookie

00:12:05.420 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,

00:12:19.240 wasn't overseeing, didn't really check what she was doing exactly. I just kind of trusted that the guy who

00:12:24.940 was prescribing, he was very experienced and credentialed and seemed like somebody who I would

00:12:31.020 go to myself to ask for a verification. Is this like a protocol? It makes sense.

00:12:35.120 And within just a couple of weeks, pick up the phone and I almost don't even recognize her. I'm

00:12:40.500 like, what mom? It's skewing in the direction of male blatantly, but she couldn't really tell.

00:12:47.240 And what dose was she on? I don't remember exactly what the dose was because it was like a cream and

00:12:53.080 the compound in creams can vary, like you said. So, but whatever it was, it was one of the

00:12:58.820 practitioners that promotes 200 to 300 total tests in females, which is insane. 0.94

00:13:05.440 Well, it might be worth talking about that for a second. I mean, we'll go back and talk more about

00:13:08.400 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

00:13:17.780 for estrogen and progesterone in the use of women. The thinking with testosterone is that

00:13:23.320 when a woman enters perimenopause, not only does she experience the predictable drop in estrogen

00:13:29.640 and progesterone, but with it, so too goes testosterone. And of course, the rationale is

00:13:34.600 that testosterone is still a very important hormone in women. I've pointed this out many times

00:13:39.860 before, but the units that are used to represent estrogen and testosterone are very misleading

00:13:45.620 because they're not the same. So if you convert them to the same units, you will see that even in

00:13:51.880 a woman, her testosterone is significantly higher than her progesterone and estrogen. So if you took

00:13:58.440 a mid follicular estrogen level, an estradiol level, and took it out of picograms per deciliter and put

00:14:06.340 everything in nanograms per deciliter, her testosterone as a premenopausal woman would 1.00

00:14:12.720 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

00:14:25.400 thinking is, well, we should replace it. And the question is to what? Now I've never heard a compelling

00:14:30.820 case for why it should be replaced to a level that exceeds her physiologic limit in her thirties, 0.94

00:14:37.360 for example. And I've never seen a woman in her thirties with a total testosterone between two and 0.77

00:14:43.980 300 nanograms per deciliter. In other words, those levels exceed even her peak physiologic level.

00:14:50.260 So it doesn't surprise me that that would be androgenizing women. Do you understand, or do you 1.00

00:14:55.580 have a sense from the folks doing this, what their rationale is for going so high?

00:14:59.500 I think their idea is simply that this is where we achieve blatant symptom relief in everyone and

00:15:09.300 a feeling of optimization above and beyond. Like this is what it should feel like when you take

00:15:14.700 hormone replacement. And I think it's just creating a state of ultimately androgens feel pretty good if

00:15:21.460 you were just crashed or very low. And then all of a sudden you're essentially on the male proportional

00:15:27.920 equivalent of like a bodybuilder cycle or something. So I couldn't say why they do it exactly, but all I

00:15:34.260 know is it's too high and it's very, uh, common to have some of these like viralizing outcomes.

00:15:40.520 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

00:15:55.640 later and they're like, what the hell? You don't even sound the same.

00:15:58.740 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 1.00

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 0.99

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 0.59

00:16:23.200 her testosterone 15 years earlier. But you say, look, we're going to set a target of 80 to 100

00:16:28.240 nanograms per deciliter, which is sort of in the ballpark of what would be kind of 70th to 80th

00:16:33.960 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

00:16:56.800 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, 0.90

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 1.00

00:19:27.800 to testosterone for is libido, does she really need to be on mega doses of systemic testosterone 0.98

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? 1.00

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

00:20:03.520 that big of a difference.

00:20:04.940 With you or with a female? 0.99

00:20:06.060 No, with a female with like a low testosterone. 0.70

00:20:08.240 Because I was going to say in a male, I wouldn't expect it to have an effect.

00:20:10.900 No, it would make no difference in a male.

00:20:11.880 Yeah, yeah, yeah. But you're saying in a female with low testosterone, taking a couple of shots 1.00

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.

00:20:28.740 I don't even know if it exists right now.

00:20:30.780 I'm not aware, but I believe there is a clinical trial ongoing. I think it might be happening at

00:20:34.880 Baylor, but I'm not sure.

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 0.71

00:20:42.320 much.

00:20:43.260 Just because it's messy and...

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. 1.00

00:20:56.260 Yeah, interesting. 1.00

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

00:21:19.140 once in a while. And then I don't know.

00:21:22.060 Interesting.

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

00:21:53.760 almost like creamy, not a spray.

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 1.00

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

00:22:19.140 unique situation to the United States.

00:22:22.860 Not in Canada though. Don't bring it back to Canada or else you get it. 0.98

00:22:25.580 That's my point. So even across the border with our neighbors that we're otherwise pretty similar

00:22:30.880 to, DHEA is...

00:22:32.820 Schedule 1.

00:22:33.240 Yeah. Schedule 1.

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

00:22:46.680 boots with it.

00:22:47.360 Yeah. Which makes no sense.

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

00:23:15.420 banned?

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,

00:23:51.120 I came to the conclusion DHEA didn't do much.

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,

00:24:06.800 whatever backdoor.

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 0.99

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

00:24:42.660 exogenously.

00:24:43.820 How much? 25 a day?

00:24:45.020 50.

00:24:45.540 50 a day. Okay.

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? 1.00

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, 1.00

00:26:13.160 it seems to be similar depending on the woman, you know, proportionally. 0.99

00:26:17.680 But 30 to 40 out of her adrenals could be three quarters of her total testosterone. 0.94

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 1.00

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 1.00

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 1.00

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, 1.00

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. 1.00

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 0.97

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 0.98

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.

00:42:02.260 Got it.

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? 0.98

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, 0.99

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, 0.98

01:04:36.780 which is clearly bullshit. What's your understanding of this FDA ruling? 0.96

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 0.98

01:10:06.880 idiotic influencers think you should be taking and maybe put it into working out. Call me then. 0.99

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 0.71

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 0.98

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 0.68

01:20:29.560 and create the most difference? Cause you've actually sent me pictures before of pre and post 0.94

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 0.98

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, 0.74

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 0.80

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 0.98

01:22:39.340 you can call obvious bullshit. You'd be shocked how many people in the fitness industry still can't do 0.90

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. 0.85

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 0.89

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 0.99

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 0.85

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 0.94

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 1.00

01:41:04.660 bodybuilder, how would I apply this when they're stepping on stage at literally diced to the socks, 0.98

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

01:41:30.300 on stage?

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

01:42:11.640 body weight in protein without fail.

01:42:13.820 And they will hold that until the stage?

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.

01:42:30.720 Okay. Okay.

01:42:31.280 Up until a week out.

01:42:32.580 But up until a week out, they would still be taking one gram of protein per pound of body weight.

01:42:36.260 Typically.

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...

01:42:52.600 Yeah. It's basically just protein. Yeah.

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,

01:43:22.060 one gram per pound of body weight.

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 1.00

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 1.00

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. 0.91

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 0.83

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 0.93

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 1.00

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 0.79

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 0.52

02:24:12.800 the importance of getting gene testing for a limited amount of snips that are ultimately very 0.56

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 0.91

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 0.93

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 0.97

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 0.92

02:29:23.360 eating sludge vegan shit on camera every day and saying it's proven by data to be the answer to 0.64

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 0.99

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 0.84

02:31:48.560 has discovered this secret ingredient that they've been keeping from you and it's the secret to fat 0.96

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 0.77

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 0.95

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 0.99

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

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02:37:46.160 the benefits i am

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The Peter Attia Drive - February 26, 2024

#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

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