#106 How To Increase Your Testosterone Levels Naturally | Derek from MPMD

0:00Welcome back to the podcast. Today, we're exploring one of the most influential hormones in human health and performance, testosterone. Joining me for this comprehensive conversation is Derek, founder of the popular YouTube channel, More Plates, More Dates, and co-founder of Merrick Health, a company focused on personalized preventative healthcare. Derek and I recently spent an intensive eight-hour session together in Vancouver recording back-to-back podcasts where I joined him as a guest and he joined me. Today, you'll hear a deep dive into testosterone addressing critical topics like testosterone's fundamental roles in men, including muscle mass,

0:35bone density, mood regulation, libido, cognitive function, and aging. How testosterone is accurately measured, interpreted, and optimized, including distinctions between total and free testosterone and why these nuances matter. Identifying symptoms and underlying causes of low testosterone and understanding why two individuals with similar hormone levels may experience vastly different health outcomes. Lifestyle factors that significantly lower testosterone from chronic stress and poor sleep to environmental endocrine disruptors. Practical evidence-based strategies to naturally boost

1:09testosterone levels, emphasizing diet, exercise protocols, sleep optimization, and stress management. We also discuss an evidence-driven evaluation of popular testosterone-boosting supplements. Vitamin D, zinc, magnesium, ashwagandha, fenugreek, tonga-ali, and more. We highlight what truly works and what's hype. We also discuss the intricacies of testosterone replacement therapy, who should consider it, the expected benefits, potential risks, safe dosing practices, and responsible monitoring protocols.

1:41We also discuss testosterone's increasingly recognized importance for women's health, including impacts on libido, body composition, cognitive function, and athletic performance, alongside crucial considerations for therapeutic use and risk management. And finally, we have a focused exploration of testosterone's role in hair loss, the interplay with DHT, genetic predisposition, and also we discuss Derek's personal hair loss journey and proven strategies for mitigation. By the end of this episode, you will have a nuanced,

2:11scientifically robust understanding of testosterone and practical guidance on how to assess, optimize, and manage your levels effectively. Before we get started, I just want to briefly mention, if you haven't already signed up for my free weekly email newsletter, you are missing out on fascinating health, fitness, and science topics with immediately applicable insights. Just recently, we've explored the anti-cancer effects of strength training and high-intensity interval training, the surprising cognitive effects of creatine, the brain benefits of ketones, how indoor exercise impacts vitamin D levels,

2:44and even intriguing links between living near golf courses and increased Parkinson's disease risk. Sign up for my free weekly email newsletter now at foundmyfitness.com forward slash newsletter. Once again, that's foundmyfitness.com forward slash N-E-W-S-L-E-T-T-E-R newsletter. And as always, my commitment is to deliver high quality evidence-based information free from advertising. To support our continued work and to have access to exclusive content, including our

3:17members-only podcast called The Aliquot, monthly Q&As that are live with me, and also curated science digest that we send out twice a month, please consider becoming a Found My Fitness Premium member. You can learn more about that at foundmyfitness.com forward slash premium. Once again, that's foundmyfitness.com forward slash premium, P-R-E-M-I-U-M. And now, on to my discussion with Derek on all things testosterone. I'm sitting here with Derek from More Plates, More Dates. You may know him from his

3:52very large YouTube channel where he talks about all sorts of things, hormones, exercise, training. I became sort of aware of your work because you were on our mutual friends podcast, Peter Atiyah, a couple of times. Super interested in, you know, your own personal experience, but you also run a company that's a preventative health company that helps people optimize their hormones, among other things. And so, I mean, I'm excited to have a conversation with you. You've got a lot

4:24of this experience, you know, personal experience, but also experience just running this company where people are coming to your company to help optimize their hormones. And so, it's a little bit of a different episode here. As you guys know, I cite everything on the podcast, and so I'm excited to kind of dive in and talk about all things hormones with you, Derek. So, thanks for coming on the show. Thanks for having me. I really appreciate the invite.

4:51I'd love to kind of start. I want to talk about testosterone, as you know, you know, kind of discussed this earlier. You're very knowledgeable in this area. In fact, we had a conversation and I was asking you some questions and your knowledge was very impressive in terms of the scope and depth. So, all things testosterone, kind of just wanted to start with the role of testosterone in men. I mean, it's obviously fundamental for male health, but I'd love if you could kind of just outline some of the primary functions of testosterone

5:23in men. Yeah, I think at a basic level, it is the primary anabolic hormone men rely on for the sustainment or growth of muscle tissue, bone health, bone integrity, inhibiting degradation, indirectly through some of those pathways as well, insulin sensitivity. If you have worsened body composition, it becomes more difficult to handle glucose adequately.

5:57Neurological health through the aromatization in the actual tissues themselves. There's an array of things that are supported critically by testosterone and its indirect metabolite activity as well through its aromatization to estrogen. And I guess notably, but often overlooked, it's easy to forget, but in adolescence, the 5-alpha reduction to DHT, so the conversion of testosterone to DHT is necessary for full maturation, sexual differentiation, to basically reach full adult male maturity.

6:33And there's a myriad of examples where if DHT is either too low via genetic predispositions or through different means, then there is inhibited maturation. And that's where you get into some of these more unique intersex cases. But essentially, at a base level, this is the primary male, all but significantly impactful in females as well, hormone that is present at about 10x concentrations in males

7:05and kind of differentiates them in terms of sexual identity and male characteristics. I do. We are going to focus a lot on the role of testosterone in males and men, but I do kind of just briefly before we will eventually talk about females and women, but what is the major role of testosterone in women? I mean, women obviously don't make as much as men, but they do make testosterone and it does play a functional role. Yeah, yeah. And like, again, it's a non-exhaustive list that I just presented. Like, the list extends

7:40beyond into erythropoiesis, the production of red blood cells, intratesticular testosterone production, absolutely critical for fertility as well. So, and women, all but not directly analogous intra-gonadally, but elsewhere in the body, the activity of testosterone is still necessary for a lot of the same things. Cognitive health, some level of cardiovascular support, bone integrity, anabolic activity in muscle tissue, all the same stuff is still the case in women, just to a much lower magnitude. So, but similar,

8:15as you would expect, there's less of a concentration required to sustain a female musculature than a male. So, the concentration differential is about 10x, but in women, the main function of testosterone still overlaps with males, but intra-gonadally is more to facilitate as a substrate of estrogen production. So, getting that sufficient amount of aromatization into estradiol, but also the conversion into estrone, which then turns into estradiol as well, to facilitate all of the female fertility

8:51facilitated processes. So, given the role of testosterone in all these important physiological processes that you just described, everything from muscle health, bone health, neurological health, red cell production, et cetera, what about the trade-offs of testosterone? And I mentioned this because of my interest in longevity, my long interest in, you know, life expectancy and looking at, you know, life expectancy between men and women. And you really see amongst like pretty much all

9:26mammal species that the females outlive the males. Obviously, there's a lot of differences going on there, but testosterone is also something that does, you know, differentiate. There's a big difference between the levels of testosterone between males and females. So, I'm kind of curious. I know you, you think about a lot of these things, since I'm curious what your thoughts are with respect to the trade-offs of testosterone with respect to longevity. I think it would be highly speculative because obviously I would love to just point to some

10:00clear-cut literature that says, based on these studies on, you know, inhibiting IGF-1 or having really low androgen levels equals lower body weights equals longer lifespan or something to that effect that could be a common kind of denominator. But it's not as cut and dry. I do think there is some level of metabolic resource demand that is needed to actually support the infrastructure of a male

10:31that is more intensive than a female. So, I would, in general, like larger humans are going to die quicker than smaller ones, at least from what I've seen trend-wise. And in supporting that, it is something that requires more hormone production in general, which is also more intensive on all organ systems accordingly to actually facilitate and get that hormone production to the level it needs to sustain that larger human. So, that's a highly speculative take on it,

11:04but that would be part of the reason. But at a high level, if you want to extrapolate to, you know, at higher levels, androgens will be neurotoxic in a dose-dependent manner past supra-levels, it will cause cardiac remodeling in a negative manner, like all of the dyslipidemia, all of the negatives that you would hear about when it comes to anabolic steroid use, to some extent at supra-levels are going to be present from testosterone all but to a more

11:35muted extent because it's not a synthetic drug that is manipulated in a lab to create, you know, something that is not a substrate for aromatization and some of the other stuff that is protective. But that's a high level speculative take. Yeah, I mean, it's kind of a loaded question because there's probably a lot of factors at play here in terms of like the differences in life expectancy between males and females. And you're pointing out the size difference is one, you know, maybe it's the lack of estrogen, right? Not the presence of testosterone, but not a lack of

12:06estrogen. Obviously, men make estrogen, but not to the same degree as women, premenopausal women. But have you looked at any of that literature? Are you aware of it? The male castrati? So the men that are castrated? Yeah, they are osteoporotic as a consequence of a lack of sufficient aromatization into estrogen and their growth plates, the epiphyseal growth plates don't close fully because of that lack of aromatization in adolescents, which is facilitated essentially entirely by testosterone

12:40as the substrate, similar to what it is in women. But if you castrate a male in adolescence, and he no longer has intratesticular testosterone production, he is now functioning off of solely adrenal production, which is like a drop in the bucket to what you actually need to function at a high level, like you're not going to have sufficient bone development, and you are going to suffer from osteoporosis inevitably. And if those those who don't know what the castrati are, it's really interesting. So it's individuals who were had angelic singing voices. And I'm not sure where the last who the last documented one was, but it was actually more recent than many would

13:15probably think it's like, within the last 100 to 200 years. But anyways, you can listen to them on YouTube singing and some of these old audios that were recorded. And it's, you know, a youthful, angelic singing voice that comes across as somewhat and like, androgynous to some extent, and obviously going through male puberty and being subjected to male amounts of testosterone and DHT would, you know, like, quote, unquote, wreck that voice, because it's going to be masculinized and get like

13:48fully, you know, the deepening that would happen that's irreversible. So the castrati were individuals that were castrated in order to prevent them literally from going through puberty adequately. So they would actually grow into men without the full maturation that would come from androgen exposure in adolescence. And as a result, you know, they would have a lack of adequate sexual differentiation maturation and their bones would reflect that as well via the osteoporotic outcomes they underwent. Did you happen to see that their life expectancy was increased though?

14:22I mean, so, I mean, it's like you're, you're living longer, but not necessarily the quality of life is notably though. Their estrogen levels are in the ground. So you saying a second ago about the estrogen. Right. So maybe, I don't know, it's, it's interesting. Like what is it, you know? Well, it's definitely a lower capacity to build muscle and bone, which is less resource intensive and you're a smaller human. So maybe as a result, you are literally a walking, I don't know, like shell of a man essentially. So you don't require as much to sustain, but your quality of

14:55life is dramatically hindered. Right. Yeah. So you live longer, but you don't necessarily want to. Right. Yeah. So that was, it's kind of interesting. I just kind of want to get your perspective on that. So I'd love to kind of dive into an area that I know you have a lot of knowledge, you know, just based off of your, your company, Merrick Health, where you guys are really helping people optimize their hormone levels. And so I kind of want to talk a little bit about some of the best practices for measuring testosterone, interpreting the results. Could you kind of outline some of the

15:30optimal best practices for actually measuring testosterone level? So, you know, optimal timing, repeated measures, like free testosterone versus bound testosterone or total testosterone, right? Like what's the difference here? What, what do people, what should they like consider? So total testosterone is the number that most people are familiar with, which reflects the total production that can be detected in your sample of blood that was taken. So floating around how much

16:06testosterone is there inclusive of the testosterone bound to binding proteins. So just because it's in your blood though, it doesn't mean it's biologically active. If it's bound to these binding proteins produced by the liver, it could be either, uh, entirely inactive or like readily available to be dissociated, but not yet fully active as well. So you have, you know, SHBG is the primary one, sex hormone binding globulin produced by the liver. This acts as a regulator of androgenicity in the

16:41body, which is like how much androgen exposure systemically you would be exposed to. And the body has this kind of regulating mechanism to partly to make sure that, you know, females stay feminine, males stay male and regulate which tissues get which hormones when and transported around the body. Because these are, um, hydro, uh, phobic, like they're fat soluble and would not go through, uh, the blood to where you want them without some sort of carrier. So they have a, um, hydrophilic

17:14vehicle, similar to like how cholesterol will get moved around through its, you know, ApoB particles and whatnot. Um, and these binding proteins, SHBG and albumin comprise the vast majority of testosterone. Um, I think SHBG is about 60% of your total T will be bound by SHBG. And then like 38% is albumin. And then 2% to 3% roughly, depending on how much SHBG produced and some other factors is actually free testosterone. So the free testosterone number is just like freely

17:49circulating, not bound to binding proteins. And it's like ready and readily available to be used by target tissues. Um, should it bind to the androgen receptor and cause the transcriptional activity? But in general, the two numbers you care about the most are going to be the total testosterone, which is like total production reflection. So like how much are you actually capable of making, which is important. A lot of people will just say, so look at your free. Cause that's like the number of the manners is that's what's actually available to use. And that's true, but it still doesn't reflect total production capacity, which is important to assess the viability of the organ

18:24response to the pituitary output, a myriad of things. So total testosterone, total production, including that bound to binding proteins, influenced by liver health, diet, bunch of different factors, free testosterone, about two to 3% in an optimally healthy male. Typically that is just freely available to be used. And then as far as, um, measurement kind of like best practices, typically in the morning is the best testosterone is kind of, it's like a pulsatile secretion fashion. So you

18:57would see in a diurnal rhythm chart showing the secretions of testosterone throughout the day, it kind of pulses out in waves. So you would have like the biggest pulse early in the morning. And then it kind of like goes across ebbs and flows throughout the day until it reaches its low point later at night. And then as you sleep, it starts to ramp back up again. So typically the best way to assess peak levels would be early in the morning. And ideally you would have, um, not taken certain confounding variable supplements like biotin that can cross detect is,

19:31you know, estrogens and whatnot. And typically labs will provide kind of like a guideline of what not to do. But in general, the rule of thumb is, you know, go in fasted early in the morning, avoid, uh, your multivitamin probably if has biotin in or biotin containing supplements and, uh, be hydrated to reflect your actual, uh, hematology profile correctly. Cause some people incorrectly think they have a elevated, you know, hematocrit level when in reality, they're just super dehydrated when they go in. Cause they just got up, rolled out of bed and are, you know, dehydrated from hours

20:04of sleeping and, you know, not hydrating properly when they wake up and they just roll in and think that, Oh, I'm going to have a heart attack. And then I got to donate blood now, which might not be the case. So I know that's a mouthful, but early in the morning and ideally you would get a repeat measurement before you make any sort of, especially before you make any sort of choices on, uh, path forward. Cause you definitely want to get confirmation if you have a low rating or even one that's like mildly concerning. Cause again, these things can be so variable depending on

20:35so many factors that you might have a blip where it's a snapshot in time of your blood. You see, you know, a 495 total T and you think, well, that's not great. It should be closer to a thousand. That's what I hear is good. And you know, all these podcasts and whatnot. That's what my friends are at. They're at 900. Like I only have 495. I should have way more than that. And some people have as really get on testosterone shockingly, but it happens. And there are a lot of clinics that will tell you like, Oh yeah, you can get that up. Let's get this up to 900. And that's all

21:07they need to give, you know, to justify it to themselves. Um, so yeah, you definitely don't want to go off of one reading. You want to go off of symptoms and repeat measurement to confirm your findings before you even decide what the path forward is for natural interventions and assessment of what is happening at the organ level and at the hypothalamic pituitary level. So you sort of alluded to this, but like talking about reference ranges and I kind of want to get into that because like, you know, there are these like reference ranges that you see and I'm just

21:40kind of like curious, like how does a man navigate where their testosterone should be, what the reference ranges mean? How do you look at this? You, how does like, you know, how does your company look at this in respect to, uh, with respect to age, with respect to like symptoms? Let's say someone's on the lower end of the reference range, but they have no symptoms or someone's at the higher end of the range, but they have symptoms. Like how does one sort of interpret what their

22:12testosterone data shows? And, um, how does the potential for someone who's actually hypogonadal? So people that are actually not making testosterone, right? How does that sort of complicate it? Um, in general, I think, um, it does get convoluted because people will see a reference range and assume, and understandably so, like there's a lot of things that people will just say, Oh, target the top of the reference range. This is where you should be. And in general,

22:44it's not a bad recommendation often for things that modulate quality of life related outcomes. You know, like even when we talk about vitamin D, it's like, you know, you should probably be at like 60, even though the low end is like 30. Typically, if you were at 40, people would be like, you know, try and bump that up to 50 or 60 with testosterone. People think similarly and justifiably so sometimes, but often what is overlooked is the fact that the actual androgen receptor content, which is like how many androgen receptors you have in like

23:15a concentrated area or also the sensitivity of it, like what kind of transcriptional activity do you get subsequent to binding? Those things all factor into like how much of an impact the androgen has after binding to the receptor. So just because you have less testosterone than the next guy, it doesn't necessarily even mean that you have less muscle growth potential or less, you know, you know, bone support capacity or less neurological support. Like it's not guaranteed

23:46any of these things based on absolute values. It should be a combination of symptoms as well as blood values. But oftentimes too, the blood values should be superseded by symptoms. In some cases, too, because you'll have some individuals who have insensitivity at the AR. So it's not just about how sensitive are you and can you get away with lower testosterone? Some guys need higher testosterone to be able to actually function well. And they might otherwise be told, oh, you know, you don't need testosterone. Your total testosterone is 900, but they might have a,

24:18you know, super high sex hormone binding globulin that's gobbing it all up and they have a low free testosterone or their actual receptor activity after binding is like subpar or they have a, you know, gene mutation that inhibits the actual activity of it. And that's where you get into some of these convoluted cases with like, you know, the Olympic boxer and like, we're not going to go down that road. But some of these individuals who like, you know, there's a spectrum of androgenic activity that is influenced not just by the total levels on paper, but it is very much dictated by your

24:48actual response to the hormone too. Is that something that's measured readily? Like, can you measure your response to your androgen receptor activity? Is that, or is that something that's not really known and you kind of have to do some? There are like proxies for it. In general, it's very crude the way they assess if you are one of the individuals on this like spectrum of androgen insensitivity. It's literally like manual assessments essentially of like your gonadal development, which is like kind of,

25:19you know, demeaning potentially if you're somebody who is like already obviously insecure about what's happening. And then you're just subjected to some sort of like subjective analysis of like an expert who determines if you've had sufficient enough like male sexual secondary characteristic development. But in general, there are proxies for activity. And, you know, if you're somebody who has, like if you, if you looked at blood work, for example, some individuals think, oh, the guy with a natural, like 1300 total T, that's probably great. That guy is like an outlier genetic phenom.

25:54Oftentimes it's a reflection of some sort of problem. Like they need to produce more to reach adequate activity. So like sometimes the body is screaming at the testes because it's not getting adequate production to do what it needs to do. And it's resulting in you shooting out more gonadotropins to make more testosterone. So typically you will see this reflected in some sort of symptom, either through actual development in adolescence being not adequate or through biomarkers. It becomes pretty clear because there will be other factors that are clearly outlier oddities in blood work when

26:30you see somebody who is not responding adequately. What will, you mentioned the gonadotropins, like what would like the luteinizing hormone or follicle stimulating hormone FSH? What would those kind of look like in the cases where it's kind of like a red flag? I mean, it's like, these are very outlier scenarios that I'd be deviating into where people are like, you know, overshooting to try and meet some sort of physiologic activity. Like most guys are going to be falling into the bucket of, they have low gonadotropins or low response to it

27:03from age-related decline. That's more of like, you know, what most people will find relevant. So I'll start there. In general, the thing you would be looking to first is, okay, like what are your levels, your total and your free levels? Are they, do they look good? Do you have any symptoms? And let's just say you do have symptoms and you're looking at these numbers and they look, you know, okay. At that point you would be looking, um, the actual output from the pituitary is going to be dictating what the signal to your testes is to actually produce testosterone. So the LH from the

27:38pituitary signals to the lytic cells to make the intratesticular testosterone. So is that signal adequate is one thing to assess. And that has a clinical reference range. Um, but also individuals who are primary hypogonadal, uh, similar to what we talked about when it comes to assessing, you know, when women are hitting menopause, like what kind of would you look to in men, if you are not responding and producing adequate testosterone at, in the testes, like you will be trying to make more

28:09luteinizing hormone typically to try and push that signal. So it's, your body's going to recognize I'm not getting enough testosterone out of this LH that I'm making. So the signal isn't sufficient. I'm not getting enough testosterone and or enough estrogen from that to provide the negative feedback that tells me to stop making GNRH and the other, the pituitary hormones. So I would just, it would just keep shooting and trying to like probably overshoot you into adequate territory. So you would, if you were primary hypogonadal, you would see the reflection typically of high

28:40gonadotropins. Um, or you would also see some sort of like structural defects and that's where you would get into like, you know, ultrasounding for, I think the prevalence in males is like 15% of males have a varicocele. I don't know if you know what that is, but it's like varicose veins in your testes essentially. And it looks like, like twisted kind of like the same thing you would see in varicose veins in your legs. It's like in the side of like the testes and it, uh, inhibits thermoregulation and significantly impedes testosterone production locally and fertility.

29:13So that oftentimes, well, 15% of men from what I recall is the number for prevalence, pretty significant though, for something a lot of people don't know exists. And if you are, you know, doing all the lifestyle stuff and it's not working and you think you're doing everything correctly and you must need testosterone, sometimes it can be overlooked that there are structural defects. So like typically the first thing you would look to is like, am I capable at the organ of responding to the signal? And like, is the signal adequate to begin

29:44with? Because if there's like a primary hypogonadal outcome, it would be some sort of like structural response problem in the testes themselves. If that's not an issue and you've ruled out all structural problems, you know, age-related decline and is not a factor and you're, you know, otherwise, you know, everything's all accounted for from that angle. You would look upstream to the pituitary and say, okay, well, at that point, am I producing enough LH and FSH? And this is typically the outcome you would see in men, uh, not always, but like a lot of men who are kind of like not sure if they

30:18need testosterone, they'll have like a relative proportional inadequate signaling driven through a myriad of factors, including, but not limited to lifestyle, some age-related decline, toxins, exposures, exposures, a myriad of things. And that's kind of like where people have this, uh, opportunity to try and incrementally maximize all the areas in their life to try and improve the output. Cause if you have sufficient functioning organs and your output is just insufficient,

30:51you might be able to get that up to snuff to where you need it just by getting leaner, losing body fat, fixing your diet, addressing micronutrient deficiencies, um, quitting smoking, not drinking anymore, fixing your sleep, you know, all the smorgasbord of, uh, things. Yeah, we're going to, that we're going to get into a little bit, but okay. Um, what about the sex binding globulin, globulin hormone, S-B-G-H? S-H-B-G, sex, sorry, sex hormone binding globulin. Sex hormone binding globulin. Um, what about the sex hormone binding globulin? Like you're talking

31:26about like, if, if you have a lot, if you have a high level of that and it's bound up to your testosterone. Um, so because a couple of questions here, what regulates those levels and what regulates like how much of that testosterone can then get away from that, you know, binding protein and then be used to, you know, obviously exert hormonal activity. So, you know, can you, can you like dial in looking at just that binding protein itself to help kind of solve some issues?

31:59Yeah. And it gets really complicated in this regard because what a lot of people don't address is, so DHT, dihydrotestosterone, mentioned earlier how it's like the primary hormone that will determine if you reach full maturity in adolescence. Like it will still be markedly male probably if you have adequate testosterone production, but you won't get full maturation if you have, you know, zero DHT from a defect in the enzyme that encodes for five alpha reductase or something. But that hormone, the most androgenic hormone in the body that essentially determines if

32:31you fully masculinize or not, or you end up, you know, with a micropenis that has a much higher binding affinity for SHBG than testosterone does. And then testosterone has a much higher binding affinity for SHBG than estrogen does. So even though on paper, we're talking about the importance of free test versus total test, which is very important. Also very important, which most people aren't going to test in their blood is the DHT level that males will rely on through adolescence and to some extent in adulthood, potentially depending on their test levels, that is going

33:03to get gobbed up even more proportionally by SHBG. So if you have high SHBG, not only is your free test potentially inadequate despite adequate testosterone production, proportionally your free DHT, which is like the main androgenic hormone is like way more gobbed up. And this gets really rough in females because they, a lot of them are using things like combined oral contraceptives, which crank SHBG through the roof, through the liver interaction with the oral combined oral contraceptive

33:34pills, depending on which drug they're using. In general, ethanol estradiol plus some progestin, depending on how androgenic the progestin is, it'll depend on how much the SHBG goes up. But you'll see in adolescent women or women who are, you know, in full adulthood that are taking combined oral contraceptives, their total testosterone will suppress upwards of 50 to 60 percent and free testosterone upwards of like 70 to 80 percent. So they're walking around like borderline asexual, castrated by a pill essentially. And that's only with oral contraceptives?

34:07That's with oral, but like any sort of progestin that is synthetic will have negative feedback to some degree, all but much lesser so via a localized IUD releasing a levonorgestrel or something. And you're not having to take that supporting estradiol that comes compounded into it. So it depends on the format, but a lot of girls are still using the combined pill. So it's just worth noting nonetheless that when these SHBG levels are skyrocketed or even like high on, you know,

34:38a clinical reference range, if you are somebody who is like moderate, you know, tea production or low normal or whatever, like the proportional hit to your DHT getting gobbed up could be like the differential between you being symptomatic versus not as well as your free tea, even though it's proportionally less gobbed up. The DHT could be like nuked entirely essentially via the SHBG levels being high. Since we're talking about the SBGH levels, I kind of want to like, what is their lifestyle?

35:08So does age regulate that and also like lifestyle factors? Yeah. So like a common thing that people hear is when you get 30 years old, your total testosterone will decline by 1% per year. But the reality of what makes this even worse is your SHBG levels will increase year over year proportionally faster, thus making the velocity of free testosterone decreases dramatically more so proportionally. So even though total test decreases by 1% a year, your free test will

35:39decrease by up to 2% per year. And that's the one that you need to like do stuff in the body through like freely circulating activity. So it's very important and very relevant for dictating what activity you have in different tissues in the body because it's ultimately the only one that can actually bind to the receptor and do what it's supposed to do. So the SHBG levels will be dictated by age, will be dictated by liver health to some extent, will be dictated by other medications, especially oral formulations. Insulogenic signaling as well, hugely implicated. If you're on a ketogenic

36:13diet, you can absolutely expect your SHBG levels to be through the roof and your free test to be much lower. So carnivore diet guys, there's a reason they eat fruit now. It's because their free test levels were all shit and their total test levels were high and they thought it was fine. But in reality, they had like borderline hypogonadal free test levels often because they were overlooking the fact that insulogenic signaling is needed to actually get SHBG to a meaningfully reasonable level for a male. And this is also something that would be relevant for females too, right? Yeah. And these binding proteins also exist for other hormones in the body because they all

36:44function in similar ways through cargo systems and transport mechanisms in the body. Like you will have binding proteins for IGF-1. You'll have binding proteins for thyroid hormones. Like it's not uncommon to see people with like normal on paper levels for certain hormones. But then when you dig deeper, all the free hormones are like proportionally horrible because they're all bound, like the total production looks okay, but it's because it's factoring in all of these like bound up hormones that are in use, like unusable essentially.

37:16Is that something that's common? Like, I mean, would you say that's... Uh, it depends on the person and lifestyle. So, but yeah, probably, especially among women because I, you know, a lot of them are, you only have so much androgens to work with to begin with. Like your production is, you know, a 10th of males typically. And then if you are occupying all of your androgens, because, you know, essentially the SHBG is going to, with a much higher binding affinity,

37:47mop up all your DHT and testosterone, not all of it, but like a significant amount of it, if it's high in any like higher than it should be, like it will impact your like free androgenic signaling so significantly that it might put you into like the, you know, female hypogonadal equivalent territory essentially. So you could be like, it's not uncommon for girls to walk around borderline asexual or like literally no drive throughout their entire adolescence, twenties, thirties, and think it's normal. And it's just not what they're supposed to be walking around like. So in other words, like if they have, if their libido is like totally down,

38:21perhaps like they're having a harder time losing fat, gaining muscle, losing fat. Um, it might, it could come down to this, right? Bone integrity. Bone integrity. Right. Yeah. So that sounds like a bit lesser. So depending on if they're on, like, obviously, you know, if you're on a combined role contraceptive pill that has estrogen in it, you know, however much it does that to what dose, you know, you get into the nuance, but ultimately like you're inhibiting natural hormone production quite dramatically through a myriad of means. Like think about guys who are just like natural having to deal with what they deal with as is, you know, the sleep impact,

38:54the cortisol impacts, the fat impact of being, you know, obese. And then if you have women who deal with all those same problems, you're going to have all the suppressive results of all of those lifestyle things, the diet, the nutrition, the whatever. And then you also factor in medications on top of that too, that maybe men don't typically have to take to, you know, achieve contraception. Like, you know, that's typically often, I think the final blow that will like push women into like, you know, closer to low drive territory often, and almost certainly lower quality of life

39:29for a lot of them. Now, that's not to say because I think this gets misconstrued often is it's not to say don't use contraceptives at all. Like there are absolutely better ways to go about it. I'm just giving examples that I see as commonplace. No, no, it's this is great. This is great information. You know, since we're kind of talking a little bit about symptoms, let's kind of circle back to talking about like, what are the symptoms of low testosterone? You know, we're talking about men here, but like, we talked about libido, muscle mass, like what are what are like the classic symptoms that men should be looking out

40:03for? Is it something that's hard to differentiate between, okay, this is testosterone or other things? It does get tough, because as you would imagine, a lot of the lifestyle related things that lead to low testosterone will come with the decrement to quality of life just via, you know, if you have poor sleep, like you're not going to feel great because you didn't rest enough. And then you add that on top of the inhibition of, you know, your output of gonadotropins, pituitary hormones,

40:36and response to them as well. Like it's like a one to punch off in a lot of this stuff. So in general, I would look to things like libido, erection quality, obviously, that's more, you know, circulatory often, but still notable nonetheless, if you suddenly, you know, if you're not mourning wood anymore, like, you got to look into it regardless if it's circulatory or hormone mediated, might be a combination of both. You no longer are able to hold muscle as easily or build

41:07muscle as easily. You're, you know, losing strength in the gym, your recovery capacity is inhibited relative to what it was when you were younger. Mood dysregulation, irritability, and these are all like really general vague symptoms. And I would love to just say, oh, look at, you know, this exact thing will happen. But in reality, it's often a constellation of things that comes as a vicious circle effect of the, you know, factors that led to that deterioration of testosterone to begin with.

41:39Or if you were just, you know, never had reasonable testosterone to begin with, you would have probably not gone through puberty adequately to begin with. So like the genetic factors, like some of these like more outlier cases become a bit more obvious because it's like you just never really like fully masculinized in adolescence. You may have a higher voice, you know, you, a lot of those things are less relevant for the average person. For the average person, it's going to be more of these general symptoms and it's warranted to get a test at that point and just see what's up. Right. Yeah. So then that in combination with the test and things that we just talked about is

42:13kind of like where, you know, like pre-diabetic, you know, progressing towards, you know, pre-diabetes, um, insulin resistance. A lot of this stuff is going to be ultimately determined by blood work though, because a lot of people aren't going to be able to identify this autonomously reliably. So that's kind of where I'd point to the more vague stuff, like the quality of life. Like, do you notice a blatant deterioration with no other factors changed? Erection quality, you know, libido, uh, vigor, muscle mass, strength, fat, body composition, stuff like that.

42:47So you mentioned the, the, by age 30, total testosterone decreases by about 1% per year. And then you mentioned even in general, in general, right, right. On average, like, yeah, exactly. There's, and that's where I'm going to ask you. I have absolutely seen 70 year olds with, you know, 900 total T's. So, so the, the, the question is then like there, there are lifestyle factors that really can sort of modulate that, you know, general decrease or not. So maybe you can accelerate it or maybe you can slow it. Right. And I kind of want to dive into

43:18some of the, those, those lifestyle factors, like what should men avoid or try to minimize in terms of their environmental exposure or lifestyle factors that are known to accelerate the decline in testosterone and, or increase the binding protein. So there's less free testosterone, right? Anything that's going to necessarily, um, uh, regulate the ability of testosterone to exert its, you know,

43:49its function essentially. Um, I would love to bang out an exhaustive list, but forgive me, I guarantee we'll miss something, but like alcohol, you know, the direct toxicity effects of that, um, does inhibit actual, uh, steroidogenesis in the testicles themselves. It will also impact sleep dramatically, which has the vicious back end effect of, you know, inhibited, uh, output of signaling hormones, which indirectly will also impact body composition, which, you know, the whole

44:22downstream cascade of that, um, smoking, obviously not helpful. Um, how much alcohol is it? Is it like any amount or like light drinking, moderate drinking? I think like, obviously the safe answer for me is to say no drinking. I think it would be more like a dose dependent toxicity effect. And what is your capacity to handle it? Because ultimately the testes are very, uh, affected by oxidative stress.

44:53And if you're not capable of handling that adequately, like it will reflect in your inadequate output of hormones locally. So I would love to give like hard and fast numbers, but there are a lot of people who will be able to get away with like murder and probably be okay. There are some guys who like, you might be low normal, uh, function to begin with. And like that, you know, couple drinks a week, like, you know, throws off your sleep a bit and kind of pushes you over the edge. Like it all depends. Um, it is very much a spectrum. So like going from like optimal to like blatantly hypogonadal

45:26from a symptom perspective, it's not like it's just on versus off. Like your way there is a, you know, it's a transition of, you know, shittiness as you arrive to that, like worst case scenario. Um, so, uh, other things I could point to, um, if you have a totally fat deficient diet, I think that's, you know, of a macro distribution that would be reflective of something that's almost certainly going to hinder your capacity to produce hormones. Um, also if you have a void of carbohydrate intake diet, it would also be something that would inhibit freely circulating hormones from liberating

46:01themselves. Um, and lack of protein, like you would not be able to produce, you know, get as robust of a response recovering from workouts and be able to build muscle, which indirectly is going to improve body composition and improve your hormones as well. So it's all kind of like balanced diet. Don't eat bad. Um, micronutrient intake. I could definitely point to if you're deficient and not every mineral or vitamin is going to be, you know, game changing, dramatic impact on your test levels, but things like zinc, magnesium, vitamin D, like these all have a marked impact

46:35on your testosterone, either response to it or capacity to produce it. Or even like, like you've mentioned in our podcast, a conversion of vitamin D into active vitamin D, like you might think you have adequate vitamin D status via your dose you're taking that's super high, but you're not actually utilizing it, but you think you are. And that's, that's impacting your testosterone production and your response to it at the androgen receptor itself as well. So I think from a minerals and vitamin standpoint, the low hanging fruits are typically going to be like B vitamins, but in

47:07particular, like from a mineral side, you know, you have, uh, you know, magnesium zinc and the vitamin D three are going to be three things that specifically on top of the minerals and vitamins that everyone's familiar with from multivitamins and whatnot are more difficult to get in adequate doses. All but zinc is typically adequately in many multivitamins, but magnesium in particular almost never is because of the weight of it. You would be having to take a multivitamin. That's like eight to 10 capsules otherwise, which just nobody does. Um, and then the vitamin D it's fat soluble.

47:40Typically you're going to have it in like a soft gel or something, and it's not always going to be at the dose you need in the multivitamins. It's just worth noting. Um, so those are just some low hanging fruits that are, if you don't look to those as part of your micronutrient optimization strategy, like you could be overlooking low hanging fruit that debt, like is a deterioration of, you know, 100 plus nanograms per deciliter per deficient, uh, micro potentially, depending on how severe the

48:11deficiency. Um, other things I get pointed to being obese, like the worst one, probably that I probably should have mentioned first, but is like so dramatically impactful on your, uh, negative feedback to the hypothalamic pituitary axis. So by that, I mean, men who are obese and women, if you have, uh, a significant amount of fat, it is going to elevate your aromatization, which is, you know, your conversion of testosterone to estrogen. And this is more impactful in males

48:43because of how the brain gets signaled from estrogen, not testosterone directly as significantly. There's a bit of a nuance there, but in general, like you need adequate estrogen to tell your brain, okay, we're good. You don't need to make enough to sauce, more testosterone because I have enough estrogen. Like that's kind of like the downstream cascade of these metabolite conversions is you produce testosterone in order to produce other things too. And the estrogen is a very potent mediator of telling your brain, we're good. And if you have a significantly elevated amount of

49:18estrogen being converted from your testosterone that you make because of how much fat you have, you are basically achieving the proportional increase in estrogen that is much higher than the amount of testosterone substrate that led to that conversion. So you have that signal telling your brain, okay, we're good. But the amount of testosterone you actually had to begin with was not good. So that's problematic. People who are obese have, you know, upwards of, I would love to give hard and fast numbers, but it could be like significant, like half of a reference range, maybe, you know, it could be the

49:54differential between you being, you know, the quality of life of you're fine versus you're blatantly in, you know, severe deficiency. And what else could I point to? Um, what does weight loss do to, to the, to those levels? Like if you are someone that's obese and then you lose weight, does that bring you back? Yeah. As long as you are losing ideally like visceral fat and like overall fat loss is going to be very, uh, supporting of getting that ratio back into balance

50:29of your estrogen and the amount that's converted to estrogen, estradiol in particular. And once that balance is favorable because you are leaner, you will have a balanced amount of feedback to the brain that then regulates like the perfect homeostasis between, okay, now we have adequate testosterone and estrogen. So you will actually notice more testosterone being produced because it realizes to get this signal that we deem adequate, we had to produce more testosterone to get that amount of estrogen. So there's a Goldilocks zone. Of course, you can't just, you know,

51:02become, you know, a malnourished, uh, you know, low, like bodybuilder shredded person, and just continue to get this elevation and proportion. It's at some point you will end up essentially starving your body of the nutrients needed to actually support hormone production. But in general, you know, guys who are, you know, like 12, like 12 to 15% body fat ish will find that they have a increase in testosterone dramatically relative to when they were obese. And it's like super significant and how much it will improve, uh, hormone status. So, and then the sleep,

51:37I think I might've already mentioned that. Yeah. What I definitely want to dive into some of the diet things in a minute, but I wanted to ask you about, um, a couple of things for, with respect to maybe factors to avoid, um, what effect is like excessive endurance training have on testosterone? Cause I thought I came across some literature where it was a negative effect. And I wasn't sure like how robust. I think it is pretty dramatic pending and exceeds your capacity to recover. So that sounds like a weird way to answer the question, but like some people have a higher tolerance for stress

52:11and that's, you know, reliance on a bunch of different factors. But if you are somebody who is not fueling yourself correctly to handle that amount of endurance training, like you were, let's just say you're in a calorie deficit and you're trying to be like, I don't know, six pack shredded for the summer and like look as good as possible, but also fuel your like endurance event efforts. Like you're probably like not doing two, you're not doing two birds, one stone, like you're doing two things like inadequately, almost certainly, and malnourishing yourself and

52:42ending up in a state of hormone deficiency as a result. Probably like you've seen studies all, there are cases that you can point to of what happened to natural bodybuilders as they diet for a show. And you can see in like, as they start to get closer to stage ready, which is like the most shredded, basically any documented human gets essentially the requirement to get there is a state of malnourishment essentially. And at some point, typically once you start to cross into that,

53:14like, you know, single digit body fat threshold, you start to become so malnourished that you are inhibiting your actual capacity to produce hormones adequately, you almost enter into like, you know, preservation mode slash like hibernation or something. And it's kind of just like, save yourself, we're starving to death, like how do I stop everything metabolically taxing from happening? Let's shut down all systems, nor do we have the substrate to actually produce these hormones to begin with. That's kind of what happens when you get like really, really malnourished. And with endurance running, like I've seen guys out eat, you know, 5000 plus calorie per day diets when

53:48they're doing like really intensive endurance activity. So if you are not fueling adequately, and with the right fuel, micronutrient density, macro allotment, the how much of it is like carbs versus fat versus protein. Yeah, you could absolutely exercise yourself into a state of hypogonadism easily. I kind of like, I would caveat not easily. It's hard to train that hard. Right? Yeah, no, it's definitely not easily. Like, there's not a lot of people that are kudos to the people mentally strong enough to do that. Well, I kind of think of the analogy here for women,

54:22it would be like when women are excessively endurance training, and in a severe caloric deficit, and they become a meneretic, right? So they're essentially not ovulating anymore. And in fact, you mentioned like wanting to get shredded for the summer. Well, I actually in my 20s, was was doing this very thing where I mean, I was running like 10 miles a day. And I was eating like carrots and hummus. And that's it, you know, it was like, not fueling myself, no, like hardly any fat, you know, it was very, like, very sort of like, low protein, you know, low fat diet. And I definitely

54:58got shredded ish. But like, I became a meneretic for several months, you know, where I just didn't get my period. And so I wasn't ovulating. And so I had to add back the calories in the food. It was like, and it took a while. Yeah, for my body kind of like recalibrated. Yeah. But I feel like that's kind of like the analogy that like, it is, it's like your body shuts down. It's like, okay, I'm not getting enough calories. Reproduction is not essential right now survival mode, right? Not reproductive, not reproductive, like happy growth mode. It's like survival mode. And like, some people might

55:31not even realize how significant of a deterioration hormone production I'm talking about. Like to give context, men who are dieting for bodybuilding shows naturally, it is not uncommon to see the end result of a hormone profile on like the last week, them to look more female on paper than like their girlfriend. Like that's how low their testosterone levels are. That's wild. That's wild. Um, just to kind of sum up the like factors to avoid. Not always, but sometimes.

56:01Um, I wanted to get your opinion on endocrine disrupting chemicals. Like how, how have you, or has your, um, you know, your company looked or seen anything or do you have any speculation into like what the scientific literature has shown in terms of them affecting hormone levels? Yeah, I think we're pretty convinced that there is an effect. It's just the magnitude at which you often see hyped up, I think maybe over exaggerated. There are low hanging fruit things to absolutely

56:35avoid. Like don't use, you know, plastic Tupperware and like heat it up and stuff like that. Try and use glass when you can, um, try and ensure you have like high quality air if possible. Like pollution, I think is a big factor for like your body's capacity to deal with stress and like the allocation of resources to be chronically dealing with a toxic environment will inhibit systemic, like broad systems. Um, water quality, like if you can make sure you have like decent water, I think that'd be

57:07solid. But as far as like the actual magnitude of impact of those things for most people, I think is going to be relatively negligible in contrast to like the obesity, the diet, the exercise, the sleep quality, the, uh, potential, uh, carcinogens that might be exposing themselves to, you know, some of the lifestyle stuff is like way more important to be addressing as like the base infrastructure before you start thinking about like, Oh, it must be my like shower that is like shooting chlorine at me.

57:42Like it must be that, or it sure get a shower filter, but like, it's not going to be the game changer. I do think avoiding like the basics. So like, you know, switch to glass where you can don't use plastic water bottles, stuff like that. And there is blatant evidence showing interactions with estrogen receptors with some of these compounds, as well as androgen receptors, which in turn will impede the ability of the actual hormones you produce to bind to those receptors and do what it needs to do. So you're like essentially competing with yourself for activity in the body. Like you're, you know, competing with these, like, uh, even if they're

58:17like moot activity compounds, they still act as like anti-androgens or anti-estrogens via their occupying of receptors. So to whatever degree they are doing it at all is not ideal because it's inhibiting like space that could be occupied by actual endogenous hormones that you need to produce and need to work properly. And you don't want to be competing with like environmental toxins to like do things in the body. What do you, you hear, like I often hear from many people, popular, you know, media, as well as just

58:50people I speak to or comments that I read about testosterone levels being lower now in men than they have ever been. Um, for one, like, is that true? Do you think that's true? And two, like, what are some of the major contributors? Is it obesity since obesity is rampant? I mean, or is it just like everything that you mentioned all sort of like compounding together, not necessarily just like increase in, you know, BPA and plastic, you know, endocrine disrupting chemicals that are now

59:20a lot more prevalent than they were, you know, seven, 60 or 70 years ago? I did a video a while ago on like the earliest finding I could find of recorded testosterone levels in, I think it was like military soldiers or something. One thing that I think is notable is the actual detection sensitivity of testing is absolutely much different now than it was, you know, 60 years ago. So to contrast like, oh, the total test of some guy 60 years ago versus now

59:54is equivalent even on like a testing methodology basis is like flawed to begin with, because it's probably not an accurate comparison. But is there a trend downwards? I would say yes. And I think it is mostly dictated by the obesity, the diet, the lifestyle stuff. So, you know, like there's obviously things to deal with in the environment that are less favorable, and are not supportive, and probably not benign. But like, in general, I think most people that worry about this stuff, they would be put their

1:00:27mind at ease by dialing in everything else, which is not that hard to do. It's often free, or, you know, cost less money, you're like eating less food, you know, go to the gym, etc. I'm not saying that's easy to do, but like dial in your basics. And once you do that, you have like an increase, you have your baseline, let's just say you get a blood test, and you see where you're at. From there, you can start doing some of the minute changes, like putting, you know, a chlorine filter on your showerhead, do this, change your water source, whatever. Do you notice an incremental uptick in your gonadotropin output, or your response to it at that point? If yes, like, okay, maybe it was a meaningful change.

1:01:00But like, until you do that, like, you're kind of just taking shots in the dark, assuming all of these things are, you know, occupying your mental bandwidth and concerning you that may not be worth your concern to that degree. Does chlorine have an effect on testosterone? I don't, I don't like, maybe. Okay. Yeah, I think I think more of like BPA, but and consuming it, like, or like you said, hot, like heating up the plastic or like, hot beverages, like going into like something plastic. But yeah, I agree. I think that these lifestyle factors are paramount. And

1:01:31I'd love to kind of get a little bit more into some of those, particularly like, so you've already mentioned the diet. And I'm kind of, you mentioned protein, fat, carbohydrate, you know, like, so what, what, what, why are some of these important? So fats are important to make, you know, the backbones of hormones. Maybe we can talk just a little bit about like, why low fat diets and why people should be incorporating fat into their diet to make sure that they're... Yeah, like, in general, it's not like if you have, for example,

1:02:02if you ingest cholesterol, it doesn't necessarily mean you're going to have like a dose dependent elevation in your like serum cholesterol, as I'm sure everyone knows here. But there are like certain baseline requirements to serve as the substrate for producing cholesterol derived steroids in the body. And these are all ultimately derived from cholesterol and then get cleaved and manipulated through enzymatic processes to make all the hormones in your body, including but not limited to testosterone, estradiol, etc. So in general, it does seem like having a sufficient amount of fat

1:02:39is worthwhile and does seem to impact how much hormones you can actually produce. And the carbs for actually mediating, and this is going to depend on, you know, activity levels, how demanding of exercise you do, if you burn through them versus not, if you're sedentary versus not. But in general, is going to be the insulogenic signaling is somewhat necessary to facilitate a balance of free androgens, including free other hormones in the body that often go overlooked, to actually do what

1:03:11they're supposed to do, because a lot of people won't even measure the free levels of, you know, like the IGF-1, the, you know, the T3, like you'll, you know, some of this stuff gets like hyper nuanced when you get into what hormones are actually bound up that you don't realize. Um, estrogens, DHT, etc. So having a balanced diet, and then the protein, like you mentioned, um, from like a, uh, mechanistic perspective, like I think in general, these things all serve as building blocks is the simplest way I can put it and having a deficiency entirely of one or the

1:03:44other. It's just like, it's kind of the expected outcome. Like it's often not going to be ideal to be missing something entirely that your body utilizes for critical, you know, structural things. Well, it's interesting. I learned something from you because I, you know, I was aware of the importance for, you know, of, of fat, particularly like, you know, a certain amount of saturated fat, which is known to increase endogenous cholesterol production. Um, but the carbohydrates and the insulin response and like having that insulin action or response, like, and I didn't realize that

1:04:16was also important. And, you know, especially for the free, you know, hormones, like the act or the amount of free hormones. So it's, it's, it's interesting to think about like a ketogenic diet, you know, as you mentioned, like some people can really be, um, in, in a problematic state if they're on a ketogenic diet and their free testosterone just kind of tanks. And it's not to say that it will absolutely happen. Like I'm sure there are a lot of people thrive on long-term ketogenic diets or may even clinically require them. So like, I certainly

1:04:46don't want to come out here and suggest if you're on a ketogenic diet, stop doing it. Like talk to your doctor first, obviously it's just like mechanistically, this is what happens. If you have a lack of insulin signaling, you will have less capacity to suppress the binding proteins. Well, what you're saying is like, get your hormones measured, measure them right. And make sure that you're monitoring. Yeah. Be informed before you like freak out about anything. Right. Yeah. Um, with respect to other sort of like lifestyle factors that can maybe boost testosterone. So we're talking about dietary factors here. What about exercise? I, you know,

1:05:20resistance training is one that comes to my mind when I think about trying to boost testosterone. I mean, is there merit to that? Is that something that moves the needle? Yeah. I think it's kind of like in simplest way I could put it as like descending order of intensity, essentially. So like, you know, weightlifting at the top and then you have like, um, some of your more like hit style workouts underneath that. And then at the bottom of it would be like the most basic of, I don't know, barely exerting yourself, but like getting out there and moving that is going to have the least impact in general. And at the top, it's going to be, you know,

1:05:55the muscle building, facilitating processes, the things that build bone, et cetera, resistance training. That's going to be the most directly impactful, but ultimately it's also going to be what is the overall exercise regimen that you adhere to? Cause a lot of people, the problem is not even necessarily like, Oh, what's the perfect thing. Like it has to be something you enjoy enough that you'll adhere to it. So it's like adherence almost trumps optimal in some capacity. So like get the thing you can adhere to the diet model that you can adhere to. Like a lot of people,

1:06:29the, the diet that on paper is the best, it won't be the one that you stick to for more than like six weeks. It's like, don't do that one. If that's the case, cause you're not going to stick to it and then you're just going to end up where you were before. So calories trump everything, unfortunately, you know, or fortunately, cause it gives you a lot more versatility with like your choices. I think it's not like you're stuck in a myopic kind of, you know, box of, I have to be on like the Mediterranean diet or I have to be on the carnivore diet or I have to be on the vegan, you know, the whatever. There are a lot of ways to skin a cat and ultimately it's going to come in mainly from energy balance. And then also from there optimizing for, you know, having adequate

1:07:05protein, fat presence, carbohydrate balance to support your, you know, whatever exercise you're doing and the intensity of it. Um, and all the things underlying that. Yeah. Um, with respect to some of the micronutrients, it kind of, this kind of gets into the, the supplement area as well. But you mentioned some important ones that I've also kind of like come across in the literature and that being vitamin D, zinc, magnesium. Can we, can we kind of just dive a little bit into their effectiveness? Like there's like, is there human data on it? Like, do you know anything about how

1:07:40they're working? I mean, I've seen, I've read some of the, the human studies, particularly on the vitamin D and like getting like higher dose vitamin D supplementation, improving testosterone. But I mean, I'd love to kind of just take a moment to kind of talk a little bit more about that if, if you want. Yeah. Like in general, I think the most reliable things that move the needle, if you were deficient, what is, I don't know if people are familiar with the ZMA. It was like a, the first like combo supplement that was sort of seen as like a testosterone booster that was

1:08:10available in the market. And it's, you know, like zinc, magnesium, and I don't remember if the A was something else, but vitamin D is the third thing. I don't remember what the A stands for, but those are the three things that move the needle most reliably that are natural. You, you know, otherwise would get through your diet, but likely non-sufficiently. Maybe zinc you might, but like magnesium, pretty difficult. I would say for a lot of people that don't realize how deficient they are. And then even like supplementing accordingly, it's like, you know, getting one that you respond,

1:08:44that you tolerate well with your digestive system has the yield that actually produces enough magnesium from like the elemental weight of the supplement, which is not that complicated. I don't want to make it sound super complicated. Like a lot of them are fine. Rhonda has great articles on magnesium formats that are bioavailable and yield more than enough magnesium. And yeah, the vitamin D, having an adequate amount and making sure you're converting it and actually getting the activity from it. Um, mechanistically, there is some level of, um, like gene transcription capacity

1:09:17facilitated through these, like, like vitamin D is a hormone, for example. And it does also affect androgen receptor activity and some like the capacity for androgens to do what they do, not just like the production of the amount of them. So similar to what I talked about earlier, where you have this kind of like receptor interaction, how well can you actually utilize these hormones to do the things it needs to do in the body? Some of this is going to be facilitated by the adequate, uh, minerals and hormones through vitamin D supporting it. And it's not necessarily measurable as much like directly,

1:09:51but all you can really do is like backfill accordingly to hit your needs and then assess your kind of like proxies and your blood work and your symptoms and kind of go from there. In your opinion, like, let's say someone is on the deficient range of vitamin D, their inadequate magnesium, perhaps their zinc is, you know, maybe okay, or in the, in the inadequate range. Would getting to that sufficient status really move the needle with respect to like testosterone? I think if you were on the low end of the reference range or literally hypogonadal,

1:10:23and you were clinically low or deficient for those, depending if it's all three or not, because obviously there'd be an additive effect. Most of them are, I mean, at least vitamin, vitamin D, magnesium, pretty common. Yeah. Yeah. I would say like you're looking at probably a potential incremental difference of 100 to 150 total T maybe. It kind of depends on the person, of course, like I've seen more robust response in some studies, but I also don't want to like

1:10:54over-exaggerate the expectations. Um, but it is meaningful. Like it's something that happens and some of it can't be directly measured either. Like we're talking about the total T number, but it's like, how do you know how much your deficient vitamin D is impacting your ability to like use it correctly? And then even if you had the sufficient vitamin D, the magnesium impact on all that and the DNA interactions and whatnot, it's like, you know, you would have, you'd be speculating at best. So, and then there are some other more like, uh, tangential supplements that are not as like obvious no brainers that are helpful. They're just facilitating mechanisms

1:11:30that are not like, this is a vitamin you need almost regardless of what your test levels were kind of thing. Yeah. I'd love to talk about those. I mean, you hear some of these herbal supplements and like some of the ashwagandha fenugreek with Tonga Ali. I mean, let's dive into that. Like, are they effective? Which ones are effective? Which ones are hype? Yeah. Um, I think one that I would, would be worth mentioning all, but the literature isn't super robust. It is a boron.

1:12:01So that potentially has a suppressive effect on SHBG levels. There's some literature that looks promising all, but I wouldn't hang my hat on and say it's a guarantee. It's going to suppress your SHBG from like the high end of the reference range to something that's like much more, you know, much better, but like it may, it does seem to work for some people. And in general, it can be a supporting adjunct that some people are, it's not something you typically get through your diet and like significant quantities anyways. Like often people will, it'll come into multivitamin

1:12:34typically, but the quantity that moves the needle for SHBG, I believe it was like six to 12 milligrams and can be meaningful for actually liberating free testosterone, not for actually producing more total tea. Um, the other one that's probably worth mentioning ashwagandha, specifically, uh, extract that is standardized to a sufficient quantity of with analyze and not just your standard run of the mill generic ashwagandha. You want to look for ideally a patented, you know, uh,

1:13:05sensorial or a KSM 66. These are patented formats of ashwagandha that are standardized to a, um, target yield. So, you know, that what you're getting is what you're supposed to be getting rather than relying on, you know, certificates of analysis from China of a generic extract. So I would. What was that compound they're standardized to again? With analytes. Okay. It's like the, it'll show right on the label of you like ashwagandha bracket standardized to X percentage

1:13:35with, with analytes. And depending on if you have KSM 66, that's 5%. Sensorial is 10%. The difference between why you would pick one or the other is the actual total dose. You could get away with using less milligrams of the case, uh, of the sensorial because it has more with analytes per milligram inclusion in your product, but they're both like impactful. And is that, is that the active compound that affects testosterone? Yeah, it seems to be. And when I say testosterone, it's like the indirect

1:14:06effect via suppressing, uh, cortisol seemingly and kind of like the stress response manipulations that it can induce, which are favorable for people who are anxious, who have very stressful lifestyles, who could benefit from it, but it is not a catch all supplement that will benefit everyone. And some people that will push them into anhedonia territory, which is like a numbing of emotion. So you don't want to really, yeah, if you overdo it, it will like literally suppress your stress response so significantly that everything's just like black and white.

1:14:39What's, what's so what, what, what's a dose that would be considered overdoing it? And what's a dose that would maybe be effective for suppressing the cortisol response and indirectly affecting testosterone by not having the cortisol decreasing the testosterone? Like I would go with the clinically like supported dose for something that's efficacious. I wouldn't necessarily suggest somebody, you know, take something that's lower than what I've seen to actually work. But in general, it seems to be a cumulative effect over time. Maybe there are some

1:15:11people who might push you over the edge sooner. And like certainly it's something to be cautious of and be aware of as a disclaimer before you jump on any testosterone, augmenting supplements, just be aware of the mechanism of how it works based on your own individual biochemistry. Cause this is not something like a vitamin D that you can just sequester into sub Q fat and just like get rid of at some point. It's like, it could impact your mood regulation quite significantly for a bit, depending on like what your neurotransmitter balances at baseline. Like if you are already

1:15:42borderline, like emotionally numb as a person and you take ashwagandha, like you might literally like cease to care about anything for all I know. That sounds awful. Yeah. But I mean, for someone who is more of an anxious phenotype, like 600 milligrams, 600 milligrams, I think is the dose, but double check on that. Cause I might be misremembering. Right. I'm pretty sure. And that is impactful to the tune of upwards of another a hundred points. Seemingly I could be misremembering exactly. But it's like, I think it's triple digits pretty reliably for those who can benefit

1:16:13from it. And for some people, it's like a game changer supplement that really improves their quality of life outside of just the testosterone enhancing capacity of it. Cause some people deal with a lot of stress in their life and need that extra resilience or suppression of how much it's affecting their mental state. Like some people that can't even get to sleep because they're ruminating and they're constantly anxious and having that kind of suppressed, uh, stress response can be very, very net beneficial. And then on top of that improves their sleep and also improves their testosterone through the, uh, reduction of the kind of like glucocorticoid responses.

1:16:47And yeah, so it's, it works for sure. The literature seems sound on it. Um, some of it is funded by some of these companies that do have the patented extracts. So just be aware of that. But at least from what I've seen in blood work, anecdotally too, it seems to work. Tonkat Alley, another very notable one. This is one that, um, works for a different mechanism. It seems to be a bit more speculative how it works, but it seems to do a few things potentially. One being a minor, uh, CIRM activity potentially, and this is more speculative. CIRM is like a selective estrogen

1:17:22receptor modulator. So something that binds to estrogen receptors and either like positively or negatively modulates them in selective tissues. So there are certain tissues where it'd be more favorable to have a selective inhibition of certain hormones versus others. It would be detrimental. Like you wouldn't want to inhibit estrogens activity in bone, for example, because that would cause bone degradation. Um, having an inhibition at the hypothalamus level level may, depending on the person help increase testosterone via the inhibition of that feedback loop. Now, I don't necessarily think

1:17:56it is a CIRM that's just like the tertiary potential mechanism and it is speculative. The main mechanism that people seem to agree on that it does do suppression of SHBG to some extent, as well as the, uh, upregulation of steroidogenesis, um, intratesticularly. So like locally upregulating, I believe it's steroidogenic acute regulatory protein that basically incorporates, um, cholesterol onto the mitochondria to actually undergo these enzymatic cleaving, uh, sequences

1:18:28that results in the production of testosterone locally. So it seems to like help upregulate the process that actually, uh, enzymatically spits out testosterone essentially, uh, locally. So that one seems to work well for individuals who have high SHBG levels or, um, potentially higher estrogen levels than they, you know, as otherwise fixable via basic lifestyle changes and whatnot. Um, because everyone has their own proportion of metabolism at the end of the day. It's not always going to be optimal, even if you have what is otherwise like a great diet and lifestyle. Um,

1:19:03but also it's just like, I think it's for people who have adequate, everything looks on paper to be sufficient, but their SHBG might be a bit high or they could use a little bit of a boost. And it seems to work to the tune of a hundred to 200 nanograms per deciliter for some people. And it depends on how potent of a standardized, uh, extract you get. You want to look for one that is HPLC tested for uricominone. That's the active ingredient in Tonkat Ali that actually has the bioactive effect that you're looking for. There are a lot of Tonkat Ali supplements that just say

1:19:36Tonkat Ali, or it'll say Tonkat Ali like a hundred to one or like 10 to one or whatever. Like these are kind of meaningless numbers from what I understand, like you're not going to get a 200 to one version of a Tonkat. And even if you did, there's no indication there's any uricominone in it. So similar to the ashwagandha, you want something that actually says, this is how much of the literal ingredient that does what you're looking to get out of it in it. And here's a third party test to verify it. So. And what was that ingredient called again? Uricominone. Got it. E-U-R-Y-A-C-O-M-A-N-O-N-E,

1:20:13I think. Now, how does Tonkat Ali compare to like boron? Is it, I mean, it sounds like for men, it might be like you're getting a bigger bang because it's doing, it's working in two different ways. Yeah. That's a good question. Boron is a mineral that is, um, seems to be something that is, uh, mechanistically, I wouldn't be able to say, um, for certain what the differential is and how they affect the SHBG binding complex. Like I would be trying to, I might misremember and I don't want

1:20:47to misspeak. So. Okay. Well, yeah, it's just kind of interesting. But would, would the Tonkat Ali work in women as well, just through the SHBG or maybe the, like, I don't know, which just for off, like, off the topic here, boron has also kind of been thought to potentially be a longevity molecule as well. There's some evidence that boron may be involved in like improving aging. So when you said boron, I was like, oh, really? That sounds interesting. Yeah. I feel like that's almost like a lower hanging fruit thing. Cause it's just typically part of a multivitamin that may just not be dosed high

1:21:22enough. And you can just like stack on top and see if it has an incremental decrease to SHBG. And then the Tonkat is like more of a speculative one that you don't want to just like take until you've exhausted some of the other options, but it's like the more exotic kind of like hammer that you might want to take to the situation. If it's like your last resort before, you know, I've tried everything. My lifestyle is perfect. My diet's dialed. My micronutrients are accounted for. My sleep is good. I don't drink. I don't smoke. And my total tea is still inadequate. And I don't feel that great. Should I try some of this, like one of these exotic things

1:21:54that seems to have a reasonable safety profile and like an efficacious, you know, um, you know, impact in men and young, healthy men at that, like there are literature showing the effects in young, healthy men, not just like age related, like declined men. So notable now, as far as its impact on women, I would think mechanistically it would do a similar thing, but like, I don't have a study I could point to that says it's the same. So I would think, but I don't know. Are there, are there any others, you know, I hear about, you know, the, the fenugreek and then the,

1:22:25some of these like diasporic acid, or are there any others that are notable or would you say more hype? Um, I think a lot of those have been disproven like tribulus, diasporic acid, fenugreek. Um, one that is notable that might do something is shilajit. If you get a high quality shilajit, it may provide enough, like the actual capacity of your organ to respond to hormones is partly conditional on its ability to tolerate stress and reactive oxygen species locally too. So

1:22:55if you have more than you can deal with and you introduce a potent antioxidant to the equation, you may be able to like attenuate and neutralize the kind of like decrement to performance and kind of like net out more local hormone yield. So shilajit seems to be impactful on intratesticular antioxidant activity, but I wouldn't, uh, it's another one that requires like careful sourcing. And it's also one that's like more speculative and indirect. Cause like there are probably better

1:23:28ways to manage your antioxidant, like your antioxidant profile, I would think. So. So your top four supplements for testosterone would be? Zinc, magnesium, vitamin D, not in order, just the top three, I would say. And then I guess for impact, I would probably say like Tonkat Ali, but probably Boron would be my safer next choice just for like safety profile. Okay, great. And less, and then if you're like the anxious person at

1:24:00Ashwagandha. Yeah, Ashwagandha and just be like cognizant of what it's, how it works. Cause you, you may be able to get the benefit at a lower dose. You may be able to cycle it, um, depending on how you respond to it. Like similar to you with caffeine, like there's no hard and fast rules on all this stuff. Like there are studies you could adhere to like the protocols designed, but they're ultimately just designed by, you know, scientists who thought this was the way to do it. And like for you and your individual biochemistry, it may not be the ideal way. Right. I mean, I've been interested in Ashwagandha. I kind of experimented with it like half-heartedly like years ago. And I think I'm going

1:24:34to now bring it back into circulation. Um, because I do, I am interested in, in the stress management part of it, like lowering some of the cortisol and stress. Although I do that with exercise, but, um, if there's like a side effect of like, you know, just a little bit of testosterone boost, like that would be great, you know, for me. So I think that's going to be another experiment of mine that I try out. Um, check your blood first though. Yeah, no, I'm that's already told you I want to get my, my hormones. It's I've had them measured, but like, I don't feel confident. I haven't had

1:25:07repeated measurements. Because once you get that blood test, you're going to be like, fuck, I shouldn't have taken Ashwagandha because now I have no idea what this means. What the, what the baseline was. Yeah, no, definitely for sure. Um, but let's talk about like, let's say people are, you know, trying all these. If you do assess your cortisol stress response, I would highly recommend a Dutch test over a blood test. Why is that? Salivary cortisol levels, uh, are far more indicative of what's happening from a stress response standpoint than your like transient serum cortisol levels will be. Oh, really? Yeah. And because this is like the snapshot in time and it

1:25:43in the serum is just like not an accurate reflective measure. Um, the salivary levels will fluctuate and they get like multiple readings and they create like an average curve for you and they should map out your day as opposed to with blood. You like one big draw, the cortisol is measured one time and it's like, okay, you're like high end of normal. Like what do we do with that information? The salivary one's a little bit more indicative of like, here are multiple time points of the day. And like, here's where we'd expect you to be at these points. And like, this is how you're responding to your day stressors kind of thing. Cool. All right. And it's like less intrusive to like spit in a

1:26:19tube, you know, or whatever. Right. And do they, and do you usually, you spit in multiple times a day to kind of get that curve? Yeah. I've actually not done a Dutch test personally, but I'm pretty sure it's just, you spit in the tube. Yeah. Yeah. Okay. Um, good information. Let's kind of transition to like people that have, let's say like, we're, let's get back into the men category here that have like exhausted these natural ways. They've like, you know, perhaps lost weight or done all the lifestyle factors that we've talked about to improve their testosterone. They're both total

1:26:51and free all that above. Who should consider hormone replacement therapy? Like how does a man identify whether or not they're a good candidate? I mean, is it really just recommended for men with clinically low testosterone and symptoms or like what we kind of touched on this a little bit earlier, but I kind of want to just go into this, um, area now of actual testosterone replacement therapy. So, um, like there are definitely scenarios in which it's more obvious

1:27:24because there is a structural issue that cannot be rectified via any sort of lifestyle change or like sleep hygiene manipulation or whatever. Like if you have primary hypogonadism and you've ruled out the ultrasound, like varicose, yeah, there's no issues. You're not like cooking your testes in like a hot tub every night. You're not, uh, I don't know, like your sleep is dialed. Your micronutrient intake is on point. Also satisfactory amounts of calories. Like I think I might have probably indirectly touched on this, but like via the getting to a good body fat, like

1:27:59you still need to have an adequate amount of energy to actually meet the needs to produce hormones too. It's like adequate amount of calories, not overdoing it, not underdoing it. Um, if you've done all the stuff that we kind of like talked about and you've ruled out, um, pituitary adenoma, you've ruled out any sort of like, I don't know, like, uh, um, structural defects and signaling is adequate or even supra physiologic. And you're just not responding. Like at that point, it's kind of like,

1:28:32okay, you're, we could try hammering you with some HCG and see if we can stimulate a satisfactory response with like a manual, like extra push at the light Excel, um, or use some, you know, some of these other like augmenting, you know, steroidogenic supporting things like Tomcat or whatever. But if that's not working either, like your, your, your testes are cooked and you got to be on test at that point. Cause you're just not responding to any natural stimulation whatsoever. That is not typically the, I, the outcome of a lot of guys who end up on testosterone. A lot of guys

1:29:04end up on it through like, like secondary diet, like hypogonadal symptoms through like the pituitary either inadequate output or insufficient response to that output plus an insufficient amount coupled with it coming out of the pituitary. There's not a lot of people that are literally showing up with like your testes don't respond to whatsoever. Um, and those individuals, like it's app, it's kind of like if you've exhausted all resources, you've tried the whole manual stimulation

1:29:35directly. Cause HCG is the way you would actually test that out is you would actually look at, okay, if we actually hit your lighting cells directly with a signal and we escalate that to like the maximum degree and we use FSH to exogenous, it's like, if you're still not responding to that, like there's no saving it at that point, unless you have like such a significant amount of oxidative stress that you're just like not dealing with, but that would have been taken care of with the lifestyle stuff we mentioned. So primary hypogonadal, like you're going to probably be on exogenous testosterone and it's literally like testosterone. You can't fix it with

1:30:07any clomiphene. You can't fix it with HCG. You can't fix it with HMG. There's no other way around it. Like you're taking the literal hormone because it's the only thing that will get you testosterone. Like you can't produce it. So there's that. And there's different ways you can take it, of course, which we could get into later. But the next situation that's a bit more relevant is like the secondary hypogonadism situation where somebody has like testes that function just potentially to like a suboptimal capacity. And there might be some level of like low

1:30:39gonadotropin output, facilitate, facilitated through some level of like lifestyle or diet or whatever. Um, like Peter, for example, like he's pretty dialed and like he did a lot of stuff to try and like fix it before he went to any sort of replacement sleep hygiene is on point. Like the guy, like what else could you do when you're him? Right. He's I think 50 years old. So what he did was he used HCG, which was assessing, okay, like are the testes responding to like a manual signal? And they were, and he's like replaced his hormones entirely by using a manual LH mimic, essentially

1:31:15why his pituitary wasn't shooting out enough LH to hit the amount, like the enough stimulation he would need to produce the same amount of tests that would hit his like optimal variety of factors, age-related decline, who knows, but probably a combination of multiple things. And at that point, it's kind of like, do you want to manually backfill with signal or do you want to take hormones pending? You've done all the exhaustive, you know, uh, things to try and like check the boxes? Cause you know, some people don't care as much and don't want to check the boxes, but like

1:31:49in general, I would say it would be worthwhile to learn why you have the problem. Even if your intention is to just end up on testosterone anyway, like I wouldn't, I wouldn't delay treatment if you're symptomatic and it's like hurting your quality of life. But I also would like do some due diligence to just like assess like what's happening. And I think HCG for people who are like secondary hypogonadal is sometimes a good middle ground of assessing, like, is this a testicle functionality problem or is it like my pituitary output is not sufficient? Cause at that point you

1:32:23can kind of tell like which organ is it that's failing me here. So there's that. Um, and then like upstream to that, there's the actual hypothalamus and the GNRH output, which is the thing that stimulates the pituitary to make the LH and the FSH and throughout that whole cascade, you could have insufficient signal from that insufficient response to that signal and then insufficient pituitary output from that weakened signal and the response to it. Like it's a deteriorating thing that by the end of it, when it actually hits your testes may just be like suboptimal for your response to be

1:32:56adequate through often age-related decline, but it's a culmination of things. So certainly back to the original question, like how do you make sense of all this and decide when is the appropriate time to be on hormones versus not, that's where you'd have to work with like a really highly educated medical professional in general. Like I would not try and, uh, cowboy this yourself. Um, even trying to like learn it from, you know, online content, whatever. Like, I think it's, I think it's good to learn how this stuff works mechanistically. So you go in informed and don't end up putting on a

1:33:30haphazard regimen by a doctor who actually just wanted you on medications. Cause if you know this stuff, it's pretty easy to identify who's like a shitty clinic who just wants to like get you committed and stuck on lifelong hormone support. And you can like weed it out really quick. Even if the doctor seems well intentioned, he wants to help you, he wants to, you know, support your quality of life, says all the right things, seems professional, seems knowledgeable. If you don't know this stuff, it's kind of like you would be going in blind and assuming that's what you need to do. And a lot of people just end up on hormones and that's it. And sometimes there's nothing wrong with that. Sometimes

1:34:02that might be what you need, but sometimes people want to know what were the natural avenues I could have taken. Could I have, you know, done something else? Could I have maintained the signal from my brain to my testes this whole time? I'm just missing something. No, it's a really good point, you know, and also like talking about what any, you know, key risks and side effects are as well. So, I mean, that's, that's kind of important, but like before we get to the risks, like what kind of benefits for, can someone who is, you know, clearly like experiencing these symptoms of low testosterone expect from, you know, perhaps doing testosterone replacement therapy? I mean,

1:34:37you mentioned HCG, but I'm kind of here directing it more towards like actual testosterone replacement therapy. Um, yeah, it would be in general, if you are satisfactory in your replacement of these