Essentials: Tools for Hormone Optimization in Males | Dr. Kyle Gillett

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Welcome to Huberman Lab Essentials, where we revisit past episodes
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for the most potent and actionable science based tools for
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mental health, physical health, and performance. I'm Andrew Huberman, and
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I'm a professor of neurobiology and ophthalmology at Stanford School
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of Medicine, and now for my discussion with doctor Kyle Gillette.
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Doctor Gillette, great to have you back, Great to be back.
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Thank you.
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I'd like to begin with a question about what all
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males ought to do in order to optimize their hormones.
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What should they be doing, what should they avoid doing?
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If the goal is to have a long arc of
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healthy hormone optimization throughout the lifespan.
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There's many things that you should do. An analogy that
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I often make is when there's a brand new car
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that comes off the assembly line, you do a full
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scope of diagnostic workup, hook it up to the computer.
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And I think we should do the same thing with
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humans as well. Dear, in puberty, you know, obviously you're
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a functioning human, but I would say there's still development,
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and I think the human always develops. I don't think
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development ever ends, but you want to monitor that progress
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across a person's lifespan.
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What do you think are the key things to look
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for in blood work? I mean, testosterone is always the
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topic that comes up in the context of male hormone optimization,
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but certainly there are a lot of other hormones that
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are important as well.
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And with testosterone, you want to get either testosterone in
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an SHBG or a free testosterone.
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Could you define SHBG for our listeners please.
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It is sex hormone binding globulin. It is the protein
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that binds up all androgens and estrogen to the body.
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So the stronger the androgen, the stronger it binds. During puberty,
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strong androgens, especially DHT, which is the strongest bioidentical androgen,
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has a huge role a prominent role in secondary sexual characteristics.
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And if your SHBG is very high, then your DHT
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can run higher because it's not metabolized, but there's not
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quite as much free DHD, So you want to balance
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between a high enough free DHD and a high enough TOTALDHD.
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So, assuming that there's no major intervention, how often do
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you recommend that people get their blood work.
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Done using shared decision making with their physician. Usually a
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good follow up is about six months.
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So on a daily basis, maybe you could just take
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us through the arc of a day and push out
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some of the protocols that you use or the things
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that you'd like to see your male patients use in
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order to try and optimize their hormone status.
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I'll briefly touch on some of the lifestyle pillars to
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start diet and exercise, or the first two. In puberty.
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Sleep is particularly important, of course, but with diet and
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exercise throughout a lifespan, you want to not exclude things
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that are helping you. For example, daring puberty, if you're
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consuming dairy and then all of a sudden you cut
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out all day, dairy can help increase IGF one and
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free IGF one.
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And just for our audience, maybe you just mention what
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I what having enough IGF one can do for us
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that's beneficial is.
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It helps you grow. It helps with genital development, secondary
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sexual characteristics and long bone growth, skin growth, hair growth,
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a host of things.
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So getting an array of nutrients that include dairy. What
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other sorts of nutrients are important during development?
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You want to have adequate vitamin D. Vitamin D helps
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with testosterone production. It helps again with bone mineralization and
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stature after an age of about twenty five, and there's
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not a strict cutoff, but up to about an age
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of twenty five. Optimizing your growth hormone and IGF one
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helps with bone density and bone growth. So from the
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dietary standpoint, you want to have enough free estrogen, not
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too much when you're growing, but you want to help
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basically stockpile bone to prevent a risk of osteoporosis or
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thin bones fractures when you're older.
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I realize that some of this relates to ethics and
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allergies and things of that sort, But would you say that,
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on balance, that most people would benefit from eating a
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combination of quality proteins from animal sources and non animal
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sources fruits, vegetables, and starches. I mean, what do you think,
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for instance, about people following a pure carnivore or a
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very pure vegan diet in their twenties and thirties.
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In their late twenties, it might be a reasonable option.
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In early twenties and certainly teens, it is a horrible
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idea because it is likely to significantly decrease your free androgens,
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so you will have less testosterone actin on receptors through
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the body.
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Are there any other micronutrients or macronutrients that people in
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their twenties and thirties should emphasize.
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Fiber is going to be paramount in kind of like
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setting your set point of your gut microbiome the rest
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of your life. There is prebiotic fiber, which you could
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think of as fish food for your good gut microbiome.
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Your gut microbiome is kind of like an aquairument or
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a fish tank. Any fiber or food that you're putting
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in your gut, it's either going to it's going to
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skew your gut microbiome towards something that is more beneficial
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or more detrimental.
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And would you say that the prebiotic fiber and getting
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essential fatty acids that would be important to do throughout
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the life span or just for the people in their
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twenties and.
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Thirties throughout the lifespan, particularly important in the teenage, twenties
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thirties because it helps with brain development. You're certainly more
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of an expert than me when it comes to brain development,
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but it does continue to develop really throughout the lifespan,
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but certainly through the twenties and thirties as well.
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In a previous discussion of ours, I asked you about
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caloric restriction and testosterone, and if I recall correctly, the
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idea was that if somebody is overweight, they have an
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excess fat at a post tissue, then getting rid of
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some of that at a post tissue but through chloric
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restriction and exercise, provided it's done not too fast in
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a healthy way, is going to be beneficial for testosterone
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in the long run. But that for individual who are
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not carrying an excess of body fat, caloric restriction is
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actually going to lower testosterone. First of all, do I
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have that correct? And second, are there any addendums to
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that that you'd like to give us? Now that's correct.
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If you look at an individual in a caloric deficit,
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several changes will happen. One is that they'll have less
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building blocks for hormones. Another is that they will be
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in a catabolic state more often, so that balance of
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anabolism and catabolism will be different. They'll likely have less
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signaling from growth hormone and IGF one, and they'll also
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have the high SHBG that we defined earlier as the
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binding protein, so they're free androgens and free estrogens will
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go down now.
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What are some of the other pillars of creating the
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proper environment for hormone optimization.
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Stress is probably the next one. During both puberty but
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also the twenties and thirties, individuals are figuring out how
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they want to cope with stress and also figuring out
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what they want to choose to put their effort into.
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So if someone is overstressed, then they can have it,
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can put all the other lifestyle pillars, and then they
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stop dieting, well, they stop exercising, and everything else can
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go askew.
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What would it be some of the additional things that
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everybody should do.
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Another one is finding what your purpose is in life.
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So I call this spirit, but it's really just the
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self actualization component of Maslow's hierarchy of needs, which is
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basically your physical needs, your mental needs, and then your
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purpose in life which you really like to do.
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The idea is not to pick the end goal, is
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to pick a goal and then once you reach that goal,
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to assess and then pick another goal and so on.
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I think sometimes when people hear about picking up purpose
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of like ohing goerness, I have to define sort of
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like naming oneself, that you actually can change your goals
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and purpose over time. I'd like to take a quick
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in the morning, and I drink that basically first thing
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there with my favorite other one, which is raspberry or watermelon. Again,
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I can't pick just one flavor. I love them all.
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sample pack. I'd like to return to the key things
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that people should do, or I should say the key
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things that men should do to optimize their hormones. What
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do you think is a healthy, sustainable exercise regimen that
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anyone can follow that will also support their hormone status.
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For really vigorous exercise around three to four times a
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week is very sustainable over a long period of time.
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On top of that, you could add in three or
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four more instances of less vigorous exercise. When they study
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the effect of exercise, specifically vigorous exercise, one area that's
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been studied is vigorous exercise episodes lasting longer than an hour,
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and they usually track it by a rating of perceived exertion,
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which isn't perfect and it's not extremely actionable, but it's
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helpful for clinical science. But the takeaway from that is basically,
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do not. It is not hormonally helpful to train, especially regularly,
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train vigorously for longer than an hour.
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These days, for better or for worse, I think for worse,
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younger guys are asking about and using testosterone replacement therapy
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so called TRT. Why in the world would any male
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in his teens or twenties or even thirties, whose blood
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levels of testosterone and estrogen are at the appropriate levels,
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meaning within the normal reference range, why would they take
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exogic testosterone Given all the negative effects on fertility, some
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of the challenges that it can present, if the dosages
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aren't quite right, et cetera, why would they do that? Certainly,
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if they are not being paid for a particular endeavor,
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like they're not making money. If they are playing as sports,
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chances are they're not allowed to do that anyway. It's
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on the banned substances list. So to me it just
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seems like a crazy idea. But then again, I'm of
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a generation that really hasn't thought about doing that stuff
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until people were in their forties and fifties or even never.
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So is there ever a case for somebody in their
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twenties or thirties to take testosterone but if their blood
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levels are within the three hundred to nine hundred nanograms
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per DESO leader reference range.
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You know, everyone has their different reason as far as
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like when does the benefit outweigh the detriment? Not very
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often if you're in your twenties, and certainly probably almost
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hardly never. There's always, you know, rare cases like Coleman
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syndrome and whatnot, but almost never if you're very young.
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Okay, So for people in their twenties, thirties and beyond forties,
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et cetera, whose testosterone and estrogen levels are at the
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appropriate ratios and in within the normal reference range libido
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energy recovery, et cetera, are feeling least workable for their lifestyle.
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For those people, what can they do besides get great sleep,
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train but not too hard or too often, et cetera,
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et cetera. What are some of the things in the
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realm of supplementation that can help them optimize their testosterone
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and estrogen without suppressing their own indogenous production of testosterone
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and estrogen.
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Let's mention. Creatine is the first one. Creatine is interesting
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because it has multiple different effects. That helps with amino
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acid synthesis. It also helps with oxidative stress. It can
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also serve as the backup fuel tank for your monochondria,
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so kind of holding backup atp and it does slightly
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increase total testosterone and it also increases the conversion of
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testosterone to die hydro testosterone, so potentially it's especially useful
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in men in their even their teenage years and their twenties.
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You mentioned the conversion of testosterone to dihydrag testosterone, and
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there is mythology out there that creatine can increase hair loss.
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I'm guessing because there's at least one study showing that
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creatine can increase DHD dihydrad testosterone, and DHD is one
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of the primary hormones that can promote mail pattern baldness.
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So the question therefore is does create creatine supplementation increase
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the rate of hair.
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Loss in each individual? Preventing hair loss is a very
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poor reason to creatine because it's not going to take
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you to a supra physiologic level. It's not going to
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increase your androgens to an unnormal level of binding. So
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I feel like this, if that was a reason to
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not take creatine for hair loss, then.
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That means sorry, you mean hair loss is not a
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reason to avoid taking creatine.
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Correct hair loss is not a reason to avoid taking creatine.
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Think of it as just bringing you to what you
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are naturally inclined to have. If your conversion of testosterone
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to DHD is already high, then often creatine does not
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affect this. It just kind of resets your balance between
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testosterone being aromatized to estrogen or being five alpha reduced DHD.
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So it's not going to speed up hair loss more
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than just naturally being a male does. So in some individuals,
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it will have no effect. In some individuals for whatever reason,
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they have almost no five alpha reductase activity. It will
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return them to natural or normal.
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So what other supplement based tools. Can people consider.
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Another one we can loop in with creatine is beta en.
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Some people are non responders to creatines. You can increase
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that to ten grams, or you can use its cousin
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beta en to help with amino acid synthesis and shunting
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of energy. Along with that, I would put L carnatine
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beta en.
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Do you recall what dosage people typically would take if
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they're a creating non responder.
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One to three grams in fact, So yeah, several versions
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of creating have beta en mixed in because it helps
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with the processing of mathianine and homocysteine.
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So if somebody is already taking creatine and likes it
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and responds to it, will raise my hand such as myself.
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Would adding beta en help or is it redundant with creatine.
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Only if their homocystine is persistently elevated. And homocysteine is
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kind of like an inflammatory marker that can build up
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if you're not converting enough of it down the stream.
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How would I know just a blood test, so L carnatine,
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What are the ways to take L carnatine. I know
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that there's an oral form, so capsules, and there's injectibles,
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the injectibles, I think you need a prescription, Is that
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right correct?
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Do you need a prescript for the injectables or you
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should really get a prescription for the injectables. When you
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inject it, of course at the supervision of your doctor,
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it's usually done intramuscularly. It's an aqueous solution, so it
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does not have like an oil or a carrier oil
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in it like tr like testosterone esters do. However, if
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you inject it to superficially, it's not going to make
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a break anything. Often it just burns if you inject
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it subcutaneously, and it does not disseminate throughout the body
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as well. L carnatine potentially has localized effects if you
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inject it, if you ingest it orally, then it has
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a very low bioavailability, maybe only ten percent.
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So what are the dosages of L carnantine that one
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needs to ingest then if they want to get a benefit.
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Because I find only ten percent is being absorbed, it's
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probably a lot of L carnantine? How much should people
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take per day?
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Usually I recommend for oral L carnatine between one thousand
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milligrams and up to four or five thousand millis so.
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Onond to four maybe even five grams.
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Correct up to five grams a day. If you're on
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that much, especially if you have a dysregulated gut microbiome,
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you should be concerned with TMAO, which is a potential
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carcinogen that both carnatine and coline can convert into, and
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your gut microbiota determine how much that happens.
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Is it true that I can offset any negative effects
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of alpha gpc coline, that is NL carnatine that I
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take by ingesting garlic? Is that right?
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There's a compound in garlic called alison. I believe it's
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a l I ci in. It's also part of the
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scientific name the genus of types of garlic, and this
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can help decrease the conversion to TMAO. Berberine actually slightly
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decreases the conversion to TMO as well, probably through alteration
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of the gut microbiome, and then just optimizing your gut
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microbiome can decrease conversion. So not everyone needs allison, but
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it's something that you should certainly consider if you were
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on a hip.
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I'm going to continue to take the six hundred milligrams
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of gar like every time I take my L carnatine,
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But I'm going to skip the berberene because berberine gives
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me brutal headaches, and it makes me create carbohydrates because
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it drops my blood sugar.
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It has many other effects, including the dawn phenomenon where
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it drops your blood sugar when you're sleeping and you
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can't even realize it.
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Okay, And what we did not talk about is what
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L carnatine does.
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It's a shuttle, so I think it's named carnatine palmetell
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coenzyme A. Basically, it's it just takes nutrients from outside
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your mitochondria and puts them in. It also has a
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unique effect, well not too unique because tadalophil actually has
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this effect as well, is that it increases the density
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of the androgen receptor and the cytoplasm of your cells.
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So even if your androgen receptor sensitivity doesn't change, and
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even if you doesn't testosterone does not change, you will
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have more testosterone binding to that increased number of receptors.
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Does one need to cycle L carnatine, creatine.
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Beta ene into cycle any of those?
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What other supplements can one use to try and improve
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hormone profiles. And here I realize we're using a very
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broad brush because when we say improve hormone profiles, what
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are we really talking about? And for me, at least,
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I think about the subjective stuff. You know, do people
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feel like they are going to have more energy as
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a consequence of doing these things? Are they going to
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have the more optimized libido? Are they going to have
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more optimized recovery from exercise?
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Right?
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Because I mean, it's not clear to me that taking
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one's testosteron from six hundred to eight hundred is always
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going to be a good thing, especially if estrogen is
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increasing in parallel. That could cause issues. It could certainly
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make things better, it could certainly make things worse.
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Right, Let's briefly mention vitamin D, which is also a hormone.
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It's actually a sterile hormone and have. If you have
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deficient vitamin D and you replace it, then you will
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optimize your testosterone. It's also mentioned boron, so if you
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have a very high SHBG, boron can acutely help lower it,
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usually in a dose of five to twelve milligrams per day.
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It's not really a sustained effect, but boron is depleted
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in soils in many countries. I believe it's very high
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in soils in Grease and Turkey, so eating dates or
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raisins that are from those areas potentially have more boron.
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Boron also might be one of the reasons why the
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reference range for testosterone is much higher in those countries
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than other countries.
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And just to remind people, the SHPG sex hormone mining
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globulin is attaching to the diesosterone molecule and limiting the
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amount of so called free testosterone that's available to have
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its impact on cells. Okay, so, vitamin D three, I'm
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guessing you're talking about vitamin D three specifically when you
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say vitamin D and then boron five to twelve milligrams
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per day, right, and then what are some of the
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other things to optimize testosterone that are in supplement form.
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We can talk about things that affect the steroidogenesis cascades,
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So we could touch on ton cat ali. I know
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we've talked about that a little bit before, and.
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I'm guessing a number of people probably haven't heard that conversation.
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00:20:58.119 --> 00:21:01.960
Also known as long jack and net upregulates several different
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enzymes in this steroidogenesis cascade and by that what you
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mean if and this is another good thing to google.
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I think anybody interested in a hormone optimization should understand
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where sterol hormones come from. They come usually from cholesterol,
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and they can be shunted off to vitamin D very easily.
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They can be shunted off to testosterone or estrogens or
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progestogens quite easily as well. But tonkat helps with the
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conversion of multiple key steps where you synthesize testosterone another
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I think of it as like a coenzyme or a cofactor.
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An upregulator of these steps is insulin and IGF one.
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So a good rule of thumb is if you are
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not expecting as much growth hormone insulin and IGF one,
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for example, lower carb diets, caloric deficits, you're trying to
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cut body fat or body weight, then tonkat is going
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to be theoretically specially powerful.
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00:22:02.160 --> 00:22:04.759
What sorts of dosages of tongua do you recommend to
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00:22:04.759 --> 00:22:07.000
your patients anywhere.
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From three hundred to twelve hundred milligrams a day with tonkat,
407
00:22:11.200 --> 00:22:16.000
you need to be careful with the standardization because if
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00:22:16.039 --> 00:22:18.599
you're thinking about a general tonkat supplement, which is by
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far the most well studied. Then you're looking at the
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uryicominone content, which is a plant compound that is likely
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the main active pharmacologic effect. So that's the compound that's
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having the effect on the body. And if you standardize
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the uryicominone very very high, then theoretically you're having more
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effect at a lower dose.
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My blood work tells me that it causes an increase
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in free testosterone for me and also a slight increase
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in lutinizing hormone for me. What are some of the
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other effects on various hormones that you've observed in the
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blood work of your patients?
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Taking tongua ali tongkat can also slightly increase DHA And
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if you have a very high SHBG. Again, that's the
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protein that binds up your androgens, and estrogen's an extremely
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important protein. The higher your SHBG, the more it helps
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decrease it. So they've studied tongkat in populations with very
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normal shbgs and it does nothing for SHBG.
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Interesting, does that mean it does nothing for somebody overall?
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00:23:23.400 --> 00:23:26.200
So if somebody has SHBG that's in the normal range,
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will taking tonguat benefit them in any other way.
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00:23:29.559 --> 00:23:33.319
Yes, it'll increase their total and free testosterone.
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00:23:33.480 --> 00:23:35.920
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ag one subscription. What are some of the other hormones
457
00:24:54.559 --> 00:24:58.119
that you prescribe to your patients who do not want
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to go on testosterone replacement therapy or take exogenous DHA
459
00:25:02.440 --> 00:25:03.319
or anything like that.
460
00:25:03.680 --> 00:25:07.359
We could talk about Fidosian next. Fidosia's interesting because it's
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00:25:07.400 --> 00:25:10.319
a genus of plants. Fidosia agrestis is one of them.
462
00:25:10.359 --> 00:25:14.599
There's many others that are very interesting. That species is
463
00:25:14.839 --> 00:25:18.039
likely the most well studied. And it will increase LH,
464
00:25:18.519 --> 00:25:21.880
so I would not consider it an LH mimetic, so
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it doesn't really mimic it, but it increases the release
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of lutinizing a hormone from the pituitary that's a hormone
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00:25:27.240 --> 00:25:30.880
that binds to the LATEG cell, to the LT receptor,
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00:25:30.960 --> 00:25:34.680
kind of like HGG does, and it will increase the
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00:25:34.799 --> 00:25:36.200
release of testosterone.
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00:25:36.400 --> 00:25:39.880
What dosages do you have patient's stake. I've heard of
471
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some potential toxicity to the testicular cells.
472
00:25:43.799 --> 00:25:46.119
There is one study, and this is a rat study,
473
00:25:46.200 --> 00:25:49.599
but you can equate the dose of toxicity in rats
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00:25:49.640 --> 00:25:52.680
in humans. They did not give these rats any antioxidants.
475
00:25:53.160 --> 00:25:58.079
But it increases a couple different like pro inflammatory markers.
476
00:25:58.119 --> 00:26:01.880
One is GGT or gamma gluten transferrace comes from both
477
00:26:01.920 --> 00:26:04.839
the testes and the liver, and one is alkaline phosphatase
478
00:26:05.079 --> 00:26:08.480
also known as alk FOSS, again coming from both areas.
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00:26:08.880 --> 00:26:11.680
There are several different ways that you can attenuate this increase,
480
00:26:11.720 --> 00:26:13.400
and you can also just check to see if you
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have increased in the rat dose that equates with humans
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that had no effect. So the safe dose was an
483
00:26:20.599 --> 00:26:23.079
average of three hundred milligrams a day.
484
00:26:22.960 --> 00:26:25.599
So that would be three hundred milligrams a day in humans.
485
00:26:26.240 --> 00:26:28.920
Is the dosage that did not have toxicity.
486
00:26:29.039 --> 00:26:33.880
Correct correct, And often even if there is toxicity in rats,
487
00:26:33.960 --> 00:26:37.039
there is not toxicity humans, so it's not directly equitable,
488
00:26:37.559 --> 00:26:41.240
but to be safe, another regimen that I have people
489
00:26:41.240 --> 00:26:44.039
take is six hundred milligrams every other day or six
490
00:26:44.160 --> 00:26:47.799
hundred milligrams three times a week, often Monday, Wednesday, Friday.
491
00:26:48.279 --> 00:26:50.680
My understanding is that nowadays a lot of people are
492
00:26:50.759 --> 00:26:53.799
using testosterone. Let's not even call it replacement therapy, because
493
00:26:53.799 --> 00:26:56.480
some of these people have six hundred, seven hundred or
494
00:26:56.519 --> 00:26:59.200
even you know, eight hundred nine a gram peresile to read,
495
00:26:59.279 --> 00:27:02.599
So not replacing anything that is diminished. They're just trying
496
00:27:02.640 --> 00:27:05.599
to augment what's already there, increase what's already there. My
497
00:27:05.720 --> 00:27:09.240
understanding is that taking a low dose more frequently is
498
00:27:09.279 --> 00:27:11.680
going to be more beneficial than the kind of old
499
00:27:11.680 --> 00:27:14.119
school way of giving you know, one hundred or even
500
00:27:14.119 --> 00:27:17.160
two hundred milligrams in a single injection once every two weeks.
501
00:27:17.400 --> 00:27:19.480
Is that right? And what do you do with your patients?
502
00:27:19.599 --> 00:27:21.599
So let me give you a hypothetical. Somebody comes into
503
00:27:21.599 --> 00:27:26.680
your office. There their blood work and they have blood
504
00:27:26.720 --> 00:27:30.599
levels of let's say, six hundred anagrams per deestly or estosterone.
505
00:27:30.640 --> 00:27:34.319
Their estrogen is also in normal range. Everything else checks out,
506
00:27:34.640 --> 00:27:38.359
but they're complaining of you know, slightly diminished libido, slightly
507
00:27:38.400 --> 00:27:43.079
poor recovery from workouts, maybe you know, reduce motivation and drive,
508
00:27:43.119 --> 00:27:46.160
although no major depression. And you come to the conclusion
509
00:27:46.160 --> 00:27:50.279
that testosterone therapy. Not replacement, but testosterone therapy might be
510
00:27:50.279 --> 00:27:53.880
a good option to explore. What's a typical dosage range
511
00:27:54.119 --> 00:27:58.559
and frequency of administration range that you might consider exploring.
512
00:27:59.119 --> 00:28:02.200
Some of this depends on SHBG and free testosterone as well.
513
00:28:02.240 --> 00:28:05.039
So if that same individual had a very high SHBG,
514
00:28:05.079 --> 00:28:07.240
which again is the binding protein that binds up the
515
00:28:07.279 --> 00:28:11.000
testosterone and all androgens and estrogens, if it is extremely
516
00:28:11.079 --> 00:28:15.000
high and they have a free testosterone of two, then
517
00:28:15.000 --> 00:28:17.440
they might need a different dose because they need enough
518
00:28:17.480 --> 00:28:23.880
testosterone in order to have a normal uganadol free testosterone.
519
00:28:24.319 --> 00:28:27.799
But a general normal dosing range, especially for someone starting,
520
00:28:27.880 --> 00:28:31.000
is around one hundred to one hundred and twenty milligrams
521
00:28:31.319 --> 00:28:34.880
divided over the course of a week, usually either every
522
00:28:34.960 --> 00:28:38.160
other day or three times a week, occasionally twice a week.
523
00:28:38.680 --> 00:28:41.839
Many people with SHBG a bit higher can get away
524
00:28:41.880 --> 00:28:44.759
pretty easily with twice a week. This is assuming that
525
00:28:44.759 --> 00:28:47.200
the ester is sipienate or a nantheate.
526
00:28:46.920 --> 00:28:51.680
So two sixty milligram injections of testosteronecipientate.
527
00:28:50.759 --> 00:28:52.799
Per week, yeah, very common dosing to.
528
00:28:52.839 --> 00:28:54.799
Hit that one hundred and twenty milligrams per week as
529
00:28:54.880 --> 00:28:56.559
kind of the typical average.
530
00:28:56.160 --> 00:28:59.839
Erect and I would consider this like a physiologic yugan adult.
531
00:29:00.680 --> 00:29:04.000
For many people, even two hundred milligrams a week is
532
00:29:04.519 --> 00:29:07.200
far above the reference range. All of this is said
533
00:29:07.200 --> 00:29:10.839
with the caveat that testosterone is normally released in a
534
00:29:10.920 --> 00:29:13.400
pulsatile manner, so it's high in the morning, low in
535
00:29:13.400 --> 00:29:19.480
the evening. Whereas if you're on testosterone therapy, then you're
536
00:29:19.519 --> 00:29:22.359
going to have a steady state, so your testosterone level
537
00:29:22.400 --> 00:29:24.599
is going to be pretty much the same even in
538
00:29:24.640 --> 00:29:25.119
the evening.
539
00:29:25.480 --> 00:29:28.200
In your experience, when patients do that, they I'm guessing
540
00:29:28.240 --> 00:29:31.039
they report the normal constellation of positive effects, you know,
541
00:29:31.079 --> 00:29:35.400
improved mood, improved energy, improved sleep, recovery, et cetera. What
542
00:29:35.440 --> 00:29:38.400
are some of the hazards or things that can crop
543
00:29:38.519 --> 00:29:41.920
up in blood work or just subjectively that can be
544
00:29:41.960 --> 00:29:44.119
warning signs that even a dosage of one hundred and
545
00:29:44.119 --> 00:29:46.920
twenty milligrams divided into these two or three dosages per
546
00:29:46.920 --> 00:29:48.119
week is too high.
547
00:29:48.279 --> 00:29:51.440
So this is when you really have to be at
548
00:29:51.519 --> 00:29:55.559
least well versed in every organ system, not just the
549
00:29:55.880 --> 00:30:00.359
ganadal like you know, genital system you need do have
550
00:30:01.200 --> 00:30:06.440
you know, dermatology, prowess. Acne is very common change lots
551
00:30:06.480 --> 00:30:10.000
of different skin pathologies or even bruising can be related
552
00:30:10.000 --> 00:30:13.519
to hormone replacement. Hair Loss is very common to see
553
00:30:13.519 --> 00:30:17.880
as well mental status changes. It could occasionally it even
554
00:30:17.880 --> 00:30:21.200
induces a manic or a bipolar episode because testosterone is
555
00:30:21.240 --> 00:30:25.799
also dopaminergic, and then cardiovascularly, not just in the heart,
556
00:30:25.960 --> 00:30:30.079
but also concerns for like microvascular a schemic disease, ferret
557
00:30:30.200 --> 00:30:33.640
and build up because the estrogen also increases, and then
558
00:30:34.079 --> 00:30:37.880
fertility concerns as well, and lipid concerns too, So you
559
00:30:37.920 --> 00:30:44.240
really have to be you know, hematologist, dermatologist, cardiologists, lipidologists,
560
00:30:44.279 --> 00:30:45.200
the whole nine yards.
561
00:30:45.599 --> 00:30:51.039
So another reason or set of reasons rather to if
562
00:30:51.079 --> 00:30:54.079
one is considering using testosterone therapy to really do this
563
00:30:54.319 --> 00:30:57.960
in close communication with a really good physician, because that's
564
00:30:58.000 --> 00:30:59.519
a lot to monitor. Knowing whether or not you have
565
00:30:59.519 --> 00:31:01.759
acting or not is one thing, but knowing whether or
566
00:31:01.799 --> 00:31:04.119
not your LDL is going up, your ABOB is going up,
567
00:31:04.119 --> 00:31:05.839
that's a whole other biz. And that needs to be
568
00:31:05.880 --> 00:31:07.759
done through blood work, is what I'm hearing.
569
00:31:08.119 --> 00:31:11.839
Correct And if your physician that is managing or prescribing
570
00:31:11.920 --> 00:31:17.079
your testosterone therapy or your HRT is not well versed
571
00:31:17.079 --> 00:31:19.279
in these systems. You would want him or her to
572
00:31:19.319 --> 00:31:21.920
be part of an interdisciplinary team where they have other
573
00:31:22.000 --> 00:31:24.160
experts that can monitor those systems.
574
00:31:24.440 --> 00:31:26.880
There are males out there who want to increase their
575
00:31:26.920 --> 00:31:31.640
testosterone and other hormones, maybe growth hormone, et cetera, who
576
00:31:31.839 --> 00:31:35.599
opt to not take exogenous testosterones, no cream, no pellet,
577
00:31:35.680 --> 00:31:40.519
no no pill, no injectable scipionate, but decide to take
578
00:31:40.720 --> 00:31:44.720
chlmophin a couple times a week. My understanding, I've never
579
00:31:44.720 --> 00:31:46.839
done this, I would say if I had. My understanding
580
00:31:46.920 --> 00:31:52.240
is that taking chlomophin maybe two fifty milligram tablets a week,
581
00:31:52.359 --> 00:31:55.079
is what I hear people are doing, will increase what
582
00:31:55.279 --> 00:32:00.519
lutinizing hormone, the various estrogen receptor subunits. Did you explain
583
00:32:00.559 --> 00:32:03.640
how chomophin would benefit anyone and is this a good strategy.
584
00:32:03.920 --> 00:32:06.039
I'm hearing that it's being done quite a lot now.
585
00:32:06.559 --> 00:32:09.839
It will increase testosterone in a dose to pendent manner,
586
00:32:10.359 --> 00:32:13.359
but it has many other pharmacodynamic effects, which is the
587
00:32:13.359 --> 00:32:16.119
effect of the drug on the body other than its
588
00:32:16.160 --> 00:32:19.440
effect on the hypothalamus in the pituitary so in the hypothalamus,
589
00:32:19.480 --> 00:32:24.720
and the pituitary. It does what's called negative feedback inhibition,
590
00:32:26.240 --> 00:32:29.720
or it blocks the axgen of estrogen, so it crowds
591
00:32:29.759 --> 00:32:34.400
out estrogen from the estrogen receptor on the hypothalamus and
592
00:32:34.440 --> 00:32:35.240
the pituitary.
593
00:32:35.480 --> 00:32:38.359
Why would I want to take something that would increase
594
00:32:38.480 --> 00:32:42.119
the activity of an estrogen receptor. I just can't find
595
00:32:42.160 --> 00:32:43.160
the rationale for that.
596
00:32:43.559 --> 00:32:47.000
The main rationale behind taking a serm is as a
597
00:32:47.319 --> 00:32:51.720
very temporary measure that is not going to suppress pituitary
598
00:32:51.960 --> 00:32:57.039
or hypothlemic function. If your testosterone is just so drastically
599
00:32:57.079 --> 00:33:01.000
low that it is unlikely to recover anyone anyway. So
600
00:33:01.240 --> 00:33:04.680
most of the time it is not clinically useful and
601
00:33:05.720 --> 00:33:08.759
SERMs should not be prescribed very often, certainly not as
602
00:33:08.880 --> 00:33:14.720
long term testosterone replacement or testosterone optimization in most individuals.
603
00:33:14.759 --> 00:33:20.359
There's always exceptions to everything. But there's five different estrogen
604
00:33:20.519 --> 00:33:26.079
and estrogen related receptors. There's two main estrogen receptors and chlomid,
605
00:33:26.200 --> 00:33:30.119
and every serm has a very unique profile because they
606
00:33:30.240 --> 00:33:34.400
selectively inhibit some receptors in some tissues but not other
607
00:33:34.440 --> 00:33:39.039
receptors and other tissues. For example, chlomid can inhibit receptors
608
00:33:39.039 --> 00:33:42.680
that are in the eye, and it can cause visual
609
00:33:42.759 --> 00:33:48.799
changes blurry vision, especially at higher doses, and it also
610
00:33:49.160 --> 00:33:51.960
acts in every other tissue with the body, so side
611
00:33:51.960 --> 00:33:56.599
effects from chlomid and other selective estrogen receptor modifiers are
612
00:33:56.720 --> 00:33:57.279
very common.
613
00:33:57.640 --> 00:33:59.559
I'd like to take a quick break to acknowledge one
614
00:33:59.599 --> 00:34:03.960
of our sauncers, David. David makes protein bars unlike any other.
615
00:34:04.359 --> 00:34:07.799
Their newest bar, the Bronze Bar, has twenty grams of protein,
616
00:34:07.920 --> 00:34:10.880
only one hundred and fifty calories and zero grams of sugar.
617
00:34:11.280 --> 00:34:13.639
I have to say these are the best tasting protein
618
00:34:13.679 --> 00:34:16.719
bars I've ever had, and I've tried a lot of
619
00:34:16.760 --> 00:34:19.480
protein bars over the years. These new David bars have
620
00:34:19.480 --> 00:34:22.599
a marshmallow base and they're covered in chocolate coating, and
621
00:34:22.679 --> 00:34:26.519
they're absolutely incredible. I of course eat regular whole foods.
622
00:34:26.519 --> 00:34:29.480
I eat meat, chicken, fish, eggs, fruits, vegetables, et cetera.
623
00:34:29.880 --> 00:34:31.480
But I also make it a point to eat one
624
00:34:31.559 --> 00:34:34.039
or two David bars per day as a snack, which
625
00:34:34.119 --> 00:34:36.079
makes it easy to hit my protein goal of one
626
00:34:36.079 --> 00:34:38.440
gram of protein per pound of body weight, and that
627
00:34:38.519 --> 00:34:40.920
allows me to take in the protein I need without
628
00:34:40.920 --> 00:34:44.559
consuming excess calories. I love all the David bronze bar flavors,
629
00:34:44.800 --> 00:34:48.880
including cookie dough, caramel chocolate, double chocolate, peanut butter chocolate.
630
00:34:49.039 --> 00:34:51.960
They all actually taste like candy bars. Again, they're amazing,
631
00:34:52.280 --> 00:34:54.360
but again they have no sugar, and they have twenty
632
00:34:54.400 --> 00:34:57.000
grams of protein with just one hundred and fifty calories.
633
00:34:57.440 --> 00:34:59.320
If you'd like to try David, you can go to
634
00:34:59.440 --> 00:35:02.679
David prote dot com slash huberman. Right now, David is
635
00:35:02.679 --> 00:35:05.079
offering a deal where if you buy four cartons, you
636
00:35:05.119 --> 00:35:07.320
get the fifth carton for free. You can also find
637
00:35:07.400 --> 00:35:10.320
David on Amazon or in stores such as Target, Walmart,
638
00:35:10.360 --> 00:35:12.920
and Kroger. Again, to get the fifth carton for free,
639
00:35:13.039 --> 00:35:17.480
go to David Protein dot com slash huberman. Alcohol. Does
640
00:35:17.519 --> 00:35:21.039
it increase a romantase the enz on the converse distosterone
641
00:35:21.039 --> 00:35:24.960
into estrogen or not? And is there a dose dependence there?
642
00:35:25.559 --> 00:35:29.119
It significantly? Does there is a dose dependence? In general,
643
00:35:29.599 --> 00:35:34.320
I would not recommend more than three to four, you know,
644
00:35:34.400 --> 00:35:38.159
standard drinks. One huge glass of wine is probably five
645
00:35:38.239 --> 00:35:41.400
standard drinks every two weeks. The other thing to keep
646
00:35:41.400 --> 00:35:43.559
in mind with alcohol is as a lot of calories
647
00:35:43.719 --> 00:35:47.000
seven kilo calories program almost as much as fat which
648
00:35:47.039 --> 00:35:50.079
is nine. And then it's also very gaba urgic, so
649
00:35:50.800 --> 00:35:57.280
it can activate inhibitory neurotransmission, and that can also affect
650
00:35:57.320 --> 00:36:01.480
how many how much LH and FSH is released, so
651
00:36:01.519 --> 00:36:06.039
that can also decrease testosterone, almost kind of similar to
652
00:36:06.159 --> 00:36:09.079
how opiates can decrease testosterone.
653
00:36:09.199 --> 00:36:11.760
I want to go back to the prostate and talk
654
00:36:11.760 --> 00:36:14.639
to you about something that's kind of a newer emerging trend.
655
00:36:14.760 --> 00:36:16.800
I know that you've talked to a little bit about
656
00:36:16.800 --> 00:36:20.519
this in previous podcasts that a number of men, I
657
00:36:20.519 --> 00:36:24.519
should say a number of physicians are prescribing low dose
658
00:36:24.599 --> 00:36:28.360
to dalophil also known as cialis, to their male patients,
659
00:36:28.599 --> 00:36:31.199
so in dosage ranges of like two point five milligrams
660
00:36:31.239 --> 00:36:34.079
to five milligrams per day, but not for a rectile dysfunction,
661
00:36:34.159 --> 00:36:37.760
but rather for improving prostate health, and presumably they get
662
00:36:37.800 --> 00:36:40.320
sort of a boost in terms of blood flow to
663
00:36:40.360 --> 00:36:43.880
the genitalia as well, but again not specifically a deal
664
00:36:43.920 --> 00:36:47.679
with a rectile dysfunction, but to deal with prostate health
665
00:36:47.760 --> 00:36:50.400
and blood flow to the prostate. Is that something that
666
00:36:50.440 --> 00:36:54.199
you sometimes often prescribe to your patients, and of what age?
667
00:36:54.559 --> 00:36:58.159
Toad Alifil is a very underrated medication. The age would
668
00:36:58.199 --> 00:37:02.440
kind of depend on the indication, So ted aalaphil is
669
00:37:02.559 --> 00:37:05.719
also a blood pressure medication. It can very slightly decrease
670
00:37:05.719 --> 00:37:09.440
blood pressure, especially at higher doses. At higher doses at
671
00:37:09.519 --> 00:37:12.800
theorem a high dose would be twenty miligrams, not two
672
00:37:12.800 --> 00:37:17.079
point five miligrams, but consistently it can somewhat affect with
673
00:37:17.199 --> 00:37:19.199
the cones in the eye that have to do with
674
00:37:19.280 --> 00:37:21.920
red and green sight, although if you remove it, that
675
00:37:22.000 --> 00:37:25.079
effect is reversed. So basically, if you don't need really
676
00:37:25.079 --> 00:37:27.760
really good red green discrimination, you can take higher doses,
677
00:37:28.159 --> 00:37:31.239
but in general I recommend no higher than ten miligrams
678
00:37:31.239 --> 00:37:37.280
a day, usually just two or five miligrams. One other
679
00:37:37.440 --> 00:37:40.440
benefit or other use of tadalophil is that it increases
680
00:37:40.519 --> 00:37:44.320
the density of the androgen receptor, similarly to L carnotine,
681
00:37:45.599 --> 00:37:48.840
so that's an interesting benefit. Another benefit is that if
682
00:37:48.880 --> 00:37:51.679
you give it to people with nolturia, which is urinating
683
00:37:51.719 --> 00:37:54.480
at night, in general, it will cut the episodes in half,
684
00:37:54.639 --> 00:37:57.199
so it could go from two to one, which can
685
00:37:57.239 --> 00:38:00.000
make a big difference for your sleep, which will secondarily
686
00:38:00.079 --> 00:38:02.760
make a big difference for your growth. Hormone and intostosterone optimization.
687
00:38:03.119 --> 00:38:05.920
Interesting. So you said two point five to five milligrams
688
00:38:05.920 --> 00:38:09.440
per day is kind of typical for these prostate enhancing effects. Yes,
689
00:38:10.000 --> 00:38:13.800
I get a lot of questions about drugs to offset
690
00:38:13.840 --> 00:38:16.320
hair loss. Most of those drugs are going to operate
691
00:38:16.360 --> 00:38:19.000
through the DHD system, the DEHYDRAGSI stosterone system for the
692
00:38:19.039 --> 00:38:21.280
reasons we talked about before, DHG receptors being on the
693
00:38:21.280 --> 00:38:24.199
scalp and causing beard growth on the face. Is it
694
00:38:24.280 --> 00:38:27.440
the case that a number of people taking things like
695
00:38:27.519 --> 00:38:31.519
Propecia and other things to block the DHT or disrupt
696
00:38:31.559 --> 00:38:36.360
the DHT pathway are going to experience diminished sex drive,
697
00:38:36.440 --> 00:38:40.800
diminished you know, kind of motivation and general vigor. And
698
00:38:40.840 --> 00:38:44.320
if so, are there alternatives like topical DHT antagonists that
699
00:38:44.360 --> 00:38:47.440
they might use if they want to keep their hair
700
00:38:47.840 --> 00:38:49.320
but not have those negative effects.
701
00:38:50.000 --> 00:38:53.559
Many people that have just a bit of predisposition, they
702
00:38:53.599 --> 00:38:58.760
can use things that are topical anti androgens. Ketoconazola is
703
00:38:58.760 --> 00:39:00.920
one of them. Caffeine is actually another one.
704
00:39:01.000 --> 00:39:03.480
Wait, you have to explain how this works. How do
705
00:39:03.559 --> 00:39:05.519
people get caffeine into the hair of ollicle?
706
00:39:05.920 --> 00:39:10.280
Topically, the caffeine enters the scalp and crowds out like
707
00:39:10.559 --> 00:39:13.679
somewhat crowds out the androgen. It is a weak effect.
708
00:39:14.280 --> 00:39:18.239
It's likely just strong enough to be clinically significant. Usually
709
00:39:18.280 --> 00:39:22.119
caffeine is put into formulations with other things like ketoconazol
710
00:39:22.320 --> 00:39:26.960
that are also weak anti androgens. Of notes, spronlactone can
711
00:39:27.039 --> 00:39:30.599
be prescribed topically, but it is absorbed systemically because the
712
00:39:30.639 --> 00:39:34.519
size of the molecule, So unless your doctor specifically prescribes
713
00:39:34.559 --> 00:39:36.840
that for you, especially as a male, do not use
714
00:39:36.880 --> 00:39:42.800
topical spronalactone. Topical finasteride is also a smaller molecule, so
715
00:39:42.880 --> 00:39:47.000
it is also systemically absorbed, but it is not extremely
716
00:39:47.039 --> 00:39:51.000
well systemically absorbed. If you take topical phinasteride, then usually
717
00:39:51.039 --> 00:39:55.519
your systemic DHT will decrease by about thirty percent. Topical
718
00:39:55.559 --> 00:39:59.639
detastoride is likely a tiny bit systemically absorbed, but it's
719
00:39:59.719 --> 00:40:02.360
unique because it's half life is much faster at a
720
00:40:02.400 --> 00:40:06.440
lower dose, So topical do testeride will not affect your
721
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systemic DHD at all, And I've seen this anecdotally on
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many people on topical do testeride therapy.
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On behalf of the audience, and just for myself, thank
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you so much. You have an immense amount of knowledge
725
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and you're exquisitely good at sharing it with people in
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an actual way, So thank you, my pleasure,