Speaker 1: Welcome to Huberman Lab Essentials, where we revisit past episodes
Speaker 1: for the most potent and actionable science based tools for
Speaker 1: mental health, physical health, and performance. I'm Andrew Huberman, and
Speaker 1: I'm a professor of neurobiology and ophthalmology at Stanford School
Speaker 1: of Medicine, and now for my discussion with doctor Kyle Gillette.
Speaker 2: Doctor Gillette, great to have you back, Great to be back.
Speaker 3: Thank you.
Speaker 1: I'd like to begin with a question about what all
Speaker 1: males ought to do in order to optimize their hormones.
Speaker 1: What should they be doing, what should they avoid doing?
Speaker 1: If the goal is to have a long arc of
Speaker 1: healthy hormone optimization throughout the lifespan, there's many things that
Speaker 1: you should do.
Speaker 3: An analogy that I often make is when there's a
Speaker 3: brand new car that comes off the assembly line, you
Speaker 3: do a full scope of diagnostic workup, hook it up
Speaker 3: to the computer. And I think we should do the
Speaker 3: same thing with humans as well. Dear, in puberty, you know,
Speaker 3: obviously you're a functioning human, but I would say there's
Speaker 3: still development, and I think the human always develops. I
Speaker 3: don't think development ever ends, but you want to monitor
Speaker 3: that progress across a person's lifespan.
Speaker 1: What do you think are the key things to look
Speaker 1: for in blood work? I mean, testosterone is always the
Speaker 1: topic that comes up in the context of male hormone optimization,
Speaker 1: but certainly there are a lot of other hormones that
Speaker 1: are important as well.
Speaker 3: And with testosterone, you want to get either testosterone in
Speaker 3: an SHBG or a free testosterone.
Speaker 1: Could you define SHBG for our listeners please.
Speaker 3: It is sex hormone binding globulin. It is the protein
Speaker 3: that binds up all androgens and estrogen to the body.
Speaker 3: So the stronger the androgen, the stronger it binds. During puberty,
Speaker 3: strong androgens, especially DHT, which is the strongest bioidentical androgen,
Speaker 3: has a huge role a prominent role in secondary sexual characteristics.
Speaker 3: And if your SHBG is very high, then your DHT
Speaker 3: can run higher because it's not metabolized, but there's not
Speaker 3: quite as much free DHD, So you want to balance
Speaker 3: between a high enough free DHD and a high enough TOTALDHD.
Speaker 1: So, assuming that there's no major intervention, how often do
Speaker 1: you recommend that people get their blood work done.
Speaker 3: Using shared decision making with their physician. Usually a good
Speaker 3: followup is about six months.
Speaker 1: So on a daily basis, maybe you could just take
Speaker 1: us through the arc of a day and push out
Speaker 1: some of the protocols that you use or the things
Speaker 1: that you'd like to see your male patients use in
Speaker 1: order to try and optimize their hormones.
Speaker 2: S goattus.
Speaker 3: I'll briefly touch on some of the lifestyle pillars to
Speaker 3: start diet and exercise, or the first two. In puberty.
Speaker 3: Sleep is particularly important, of course, but with diet and
Speaker 3: exercise throughout a lifespan, you want to not exclude things
Speaker 3: that are helping you. For example, during puberty, if you're
Speaker 3: consuming dairy and then all of a sudden you cut
Speaker 3: out all dairy, dairy can help increase IGF one and
Speaker 3: free IGF one.
Speaker 1: And justin for our audience, maybe you just mentioned what
Speaker 1: I What having enough IGF one can do for us
Speaker 1: that's beneficial is.
Speaker 3: It helps you grow. It helps with genital development, secondary
Speaker 3: sexual characteristics and long bone growth, skin growth, hair growth,
Speaker 3: a host of things.
Speaker 1: So getting an array of nutrients that include dairy. What
Speaker 1: other sorts of nutrients are important during development?
Speaker 3: You want to have adequate vitamin D. Vitamin D helps
Speaker 3: with testosterone production, It helps again with bone mineralization and
Speaker 3: stature after an age of about twenty five, and there's
Speaker 3: not a strict cutoff, but up to about an age
Speaker 3: of twenty five. Optimizing your growth hormone and IGF one
Speaker 3: helps with bone density and bone growth. So from the
Speaker 3: dietary standpoint, you want to have enough free estrogen, not
Speaker 3: too much when you're growing, but you want to help
Speaker 3: basically stockpile bone to prevent a risk of osteoporosis or
Speaker 3: thin bones fractures when you're older.
Speaker 1: I realize that some of this relates to ethics and
Speaker 1: allergies and things of that sort, But would you say that,
Speaker 1: on balance, that most people would benefit from eating a
Speaker 1: combination of quality proteins from animal sources and non animal
Speaker 1: sources fruits, vegetables, and starches. I mean, what do you think,
Speaker 1: for instance, about people following a pure carnivore or a
Speaker 1: very pure vegan diet in their twenties and thirties.
Speaker 3: In their late twenties, it might be a reasonable option.
Speaker 3: In early twenties and certainly teens, it is a horrible
Speaker 3: idea because it is likely to significantly decrease your free androgens,
Speaker 3: so you will have less testosterone actin on receptors through
Speaker 3: the body.
Speaker 1: Are there any other micronutrients or macronutrients that people in
Speaker 1: their twenties and thirties should emphasize.
Speaker 3: Fiber is going to be paramount in kind of like
Speaker 3: setting your set point of your gut microbiome the rest
Speaker 3: of your life. There is prebiotic fiber, which you could
Speaker 3: think of as fish food for your good gut microbiome.
Speaker 3: Your gut microbiomes kind of like an aquarium or a
Speaker 3: fish tank. Any fiber or food that you're putting in
Speaker 3: your gut, it's either going to it's going to skew
Speaker 3: your gut microbiome towards something that is more beneficial or
Speaker 3: more detrimental.
Speaker 1: And would you say that the prebiotic fiber and getting
Speaker 1: essential fatty acids that would be important to do throughout
Speaker 1: the lifespan or just for the people in their twenties.
Speaker 3: And thirties throughout the lifespan, particularly important in the teenage,
Speaker 3: twenties thirties because it helps with brain development. You're certainly
Speaker 3: more of an expert than me when it comes to
Speaker 3: brain development, but it does continue to develop really throughout
Speaker 3: the lifespan, but certainly through the twenties and thirties as well.
Speaker 1: In a previous discussion of ours, I asked you about
Speaker 1: caloric restriction and testosterone, and if I recall correctly, the
Speaker 1: idea was that if somebody is overweight they have an
Speaker 1: excess fat at a post tissue, then getting rid of
Speaker 1: some of that at a post tissue but through chloric
Speaker 1: restriction and exercise, provided it's done not too fast in
Speaker 1: a healthy way, is going to be beneficial for testosterone
Speaker 1: in the long run. But that for individual who are
Speaker 1: not carrying an excess of body fat, caloric restriction is
Speaker 1: actually going to lower testosterone. First of all, do I
Speaker 1: have that correct? And second are there any addendums to
Speaker 1: that that you'd like to give us?
Speaker 3: Now that's correct. If you look at an individual in
Speaker 3: a caloric deficit, several changes will happen. One is that
Speaker 3: they'll have less building blocks for hormones. Another is that
Speaker 3: they will be in a catabolic state more often, so
Speaker 3: that balance of anabolism and catabolism will be different. They'll
Speaker 3: likely have less signaling from growth hormone and IGF one,
Speaker 3: and they'll also have the high SHBG that we defined
Speaker 3: earlier as the binding protein. So there are free androgens
Speaker 3: and free estrogens will go down.
Speaker 1: Now, what are some of the other pillars of creating
Speaker 1: the proper environment for hormone optimization?
Speaker 3: Stress is probably the next one. During both puberty but
Speaker 3: also the twenties and thirties, individuals are figuring out how
Speaker 3: they want to cope with stress and also figuring out
Speaker 3: what they want to choose to put their effort into.
Speaker 3: So if someone is overstressed, then they can have it,
Speaker 3: can put all the other lifestyle pillars, and then they
Speaker 3: stop dieting, well, they stop exercising, and everything else can
Speaker 3: go askew.
Speaker 2: What would it be some of the additional things that
Speaker 2: everybody should do.
Speaker 3: Another one is finding what your purpose is in life.
Speaker 3: So I call this spirit, but it's really just a
Speaker 3: self actualization component of Maslow's hierarchy of needs, which is
Speaker 3: basically your physical needs, your mental needs, and then your
Speaker 3: purpose in life, what you really like to do.
Speaker 1: The idea is not to pick the end goal, is
Speaker 1: to pick a goal and then once you reach that goal,
Speaker 1: to assess and then pick another goal and so on.
Speaker 1: I think sometimes when people hear about picking a purpose
Speaker 1: of like, oh, my goodness, I have to define sort
Speaker 1: of like naming oneself that you actually can change your
Speaker 1: goals and purpose over time. I'd like to take a
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Speaker 1: sample pack. I'd like to return to the key things
Speaker 1: that people should do, or I should say the key
Speaker 1: things that men should do to optimize their hormones. What
Speaker 1: do you think is a healthy, sustainable exercise regimen that
Speaker 1: anyone can follow that will also support their hormone status.
Speaker 3: For really vigorous exercise, around three to four times a
Speaker 3: week is very sustainable over a long period of time.
Speaker 3: On top of that, you could add in three or
Speaker 3: four more instances of less vigorous exercise. When they study
Speaker 3: the effect of exercise, specifically vigorous exercise, one area that's
Speaker 3: been studied is vigorous exercise episodes lasting longer than an hour,
Speaker 3: and they usually track it by a rating of perceived exertion,
Speaker 3: which isn't perfect and it's not extremely actionable, but it's
Speaker 3: helpful for clinical science. But the takeaway from that is basically,
Speaker 3: do not. It is not hormonally helpful to train, especially regularly,
Speaker 3: train vigorously for longer than an hour.
Speaker 1: These days, for better or for worse, I think for worse,
Speaker 1: younger guys are asking about and using testosterone replacement therapy
Speaker 1: so called TRT.
Speaker 2: Why in the world.
Speaker 1: Would any male in his teens or twenties or even thirties,
Speaker 1: whose blood levels of testosterone and estrogen are at the
Speaker 1: appropriate levels, meaning within the normal reference range, why would
Speaker 1: they take exogic testosterone Given all the negative effects on fertility,
Speaker 1: some of the challenges that it can present, if the
Speaker 1: dosages aren't quite right, et cetera, why would they do that? Certainly,
Speaker 1: if they are not being paid for a particular endeavor,
Speaker 1: like they're not making money. If they are playing a
Speaker 1: sports chances are they're not allowed to do that anyway.
Speaker 1: It's it's on the band substances list. So to me
Speaker 1: it just seems like a crazy idea. But then again,
Speaker 1: I'm of a generation that really hasn't thought about doing
Speaker 1: that stuff until people were in their forties and fifties
Speaker 1: or even never. So is there ever a case for
Speaker 1: somebody in their twenties or thirties to take testosterone? But
Speaker 1: if their blood levels are within the three hundred to
Speaker 1: nine hundred nanograms per desolat er reference range.
Speaker 3: You know, everyone has their different reason as far as
Speaker 3: like when does the benefit outweigh the detriment? Not very
Speaker 3: often if you're in your twenties, and certainly probably almost
Speaker 3: hardly never. There's always, you know, rare cases like Coleman
Speaker 3: syndrome and whatnot, but almost never if you're very young.
Speaker 1: Okay, So for people in their twenties, thirties and beyond forties,
Speaker 1: et cetera. Whose testosterone and estrogen levels are at the
Speaker 1: appropriate ratios and within the normal reference range libido energy recovery, etc.
Speaker 1: Are feeling at least workable for their lifestyle. For those people,
Speaker 1: what can they do besides get great sleep, train but
Speaker 1: not too hard or too often, et cetera, et cetera.
Speaker 1: What are some of the things in the realm of
Speaker 1: supplementation that can help them optimize their testosterone and estrogen
Speaker 1: without suppressing their own indogenous production of testosterone and estrogen.
Speaker 3: Let's mention. Creatine is the first one. Creatine is interesting
Speaker 3: because it has multiple different effects. That helps with amino
Speaker 3: acid synthesis. It also helps with oxidative stress. It can
Speaker 3: also serve as the backup fuel tank for your monochondria,
Speaker 3: so kind of holding backup atp and it does slightly
Speaker 3: increase total testosterone and it also increases the conversion of
Speaker 3: testosterone to die hydro testosterone, so potentially it's especially useful
Speaker 3: in men in their even their teenage years and their twenties.
Speaker 1: You mentioned the conversion of testosterone to dihydrag testosterone, and
Speaker 1: there is mythology out there that creatine can increase hair loss.
Speaker 1: I'm guessing because there's at least one study showing that
Speaker 1: creatine can increase DHD dihydrad estosterone and DHD is one
Speaker 1: of the primary hormones that can promote male pattern baldness.
Speaker 1: So the question therefore is does create creatine supplementation increase
Speaker 1: the rate of hair.
Speaker 3: Loss in each individual? Preventing hair loss is a very
Speaker 3: poor reason to creatine because it's not going to take
Speaker 3: you to a supra physiologic level. It's not going to
Speaker 3: increase your androgens to an unnormal level of binding. So
Speaker 3: I feel like this, if that was a reason to
Speaker 3: not take creatine for hair loss, then.
Speaker 1: That means sorry, you mean hair loss is not a
Speaker 1: reason to avoid taking creatine.
Speaker 3: Correct hair loss is not a reason to avoid taking creatine.
Speaker 3: Think of it as just bringing you to what you
Speaker 3: are naturally inclined to have. If your conversion of testosterone
Speaker 3: to DHD is already high, then often creatine does not
Speaker 3: affect this. It just kind of resets your balance between
Speaker 3: testosterone being aromatized to estrogen or being five alpha reduced DHT.
Speaker 3: So it's not going to speed up hair loss more
Speaker 3: than just naturally being a male does. So in some individuals,
Speaker 3: it will have no effect. In some individuals for whatever reason,
Speaker 3: they have almost no five alpha reductase activity. It will
Speaker 3: return them to natural or normal.
Speaker 1: So what other supplement based tools. Can people consider.
Speaker 3: Another one we can loop in with creatine is beta en.
Speaker 3: Some people are non responders to creatines. You can increase
Speaker 3: that to ten grams, or you can use its cousin
Speaker 3: beta en to help with amino acid synthesis and shunting
Speaker 3: of energy. Along with that, I would put L carnatine
Speaker 3: beta en.
Speaker 1: Do you recall what dosage people typically would take if
Speaker 1: they're a creating non responder.
Speaker 3: One to three grams in fact, So, yeah, several versions
Speaker 3: of creating have beta en mixed in because it helps
Speaker 3: with the processing of methianine and homocysteine.
Speaker 1: So if somebody is already taking creatine and likes it
Speaker 1: and responds to it, will raise my hand such as myself.
Speaker 1: Would adding beta en help or is it redundant?
Speaker 3: With creatine only if their homocystine is persistently elevated. And
Speaker 3: homocysteine is kind of like an inflammatory marker that can
Speaker 3: build up if you're not converting enough of it down
Speaker 3: the stream.
Speaker 2: How would I know just a blood test?
Speaker 1: So L carnatine, what are the ways to take L carnatine?
Speaker 1: I know that there's an oral form of capsules and
Speaker 1: there's injectibles, the injectibles.
Speaker 2: I think you need a prescription, Is that right correct?
Speaker 3: Do you need a prescript for the injectibles or you
Speaker 3: should really get a prescription for the injectables. When you
Speaker 3: inject it, of course at the supervision of your doctor,
Speaker 3: it's usually done intramuscularly. It's an aqueous solution, so it
Speaker 3: does not have like an oil or a carrier oil
Speaker 3: in it like tr like testosterone esters do. However, if
Speaker 3: you inject it to superficially, it's not going to make
Speaker 3: a rake anything. Often it just burns if you inject
Speaker 3: it subcutaneously, and it does not disseminate throughout the body
Speaker 3: as well. L carnatine potentially has localized effects if you
Speaker 3: inject it, if you ingest it orally, then it has
Speaker 3: a very low bioavailability, maybe only ten percent.
Speaker 1: So what are the dosages of lcarantine that one needs
Speaker 1: to ingest then if they want to get a benefit,
Speaker 1: Because I find only ten percent is being absorbed, it's
Speaker 1: probably a lot of L carnantine.
Speaker 2: How much should people take per day?
Speaker 3: Usually I recommend for oral L carnatine between one thousand
Speaker 3: milligrams and up to four or five thousand million, so.
Speaker 2: Wonder four maybe even five grams.
Speaker 3: Correct up to five grams a day if you're on
Speaker 3: that much, especially if you have a dysregulated gut microbiome,
Speaker 3: you should be concerned with TMAO, which is a potential
Speaker 3: carcinogen that both carnatine and coline can convert into, and
Speaker 3: your gut microbiota determine how much that happens.
Speaker 1: Is it true that I can offset any negative effects
Speaker 1: of alpha gpc colin that is NL carnatine that I
Speaker 1: take by ingesting garlic?
Speaker 2: Is that right?
Speaker 3: There's a compound in garlic called alison. I believe it's
Speaker 3: a L I ci in. It's also part of the
Speaker 3: scientific name the genus of types of garlic, and this
Speaker 3: can help decrease the conversion to TMO. Berberine actually slightly
Speaker 3: decreases the conversion to TMO as well, probably through alteration
Speaker 3: of the gut microbiome, and then just optimizing your gut
Speaker 3: microbiome can decrease conversion. So not everyone needs allison, but
Speaker 3: it's something that you should certainly consider. If you were
Speaker 3: on a HEIGHTE.
Speaker 1: I'm going to continue to take the six hunderd milligrams
Speaker 1: of gar like every time I take my L carnatine,
Speaker 1: But I'm going to skip.
Speaker 2: The berberene because berberine gives me.
Speaker 1: Brutal headaches, and it makes me create carbohydrates because it
Speaker 1: drops my blood sugar.
Speaker 3: It has many other effects, including the dawn phenomenon where
Speaker 3: it drops your blood sugar when you're sleeping and you
Speaker 3: can't even realize it.
Speaker 1: Okay, And what we did not talk about is what
Speaker 1: L carnatine does.
Speaker 3: It's a shuttle, so I think it's named carnatine palmetell
Speaker 3: coenzyme A. Basically, it's it just takes nutrients from outside
Speaker 3: your mitochondria and puts them in. It also has a
Speaker 3: unique effect, well not too unique because tadalafil actually has
Speaker 3: this effect as well, is that it increases the density
Speaker 3: of the androgen receptor and the cytoplasm of your cells.
Speaker 3: So even if your androgen receptor sensitivity doesn't change, and
Speaker 3: even if you doesn't testosterone does not change, you will
Speaker 3: have more testosterone binding to that increased number of receptors.
Speaker 2: Does one need to cycle L carnatine, creatine, beta.
Speaker 3: Ene, REO cycle any of those?
Speaker 1: What other supplements can one use to try and improve
Speaker 1: hormone profiles. And here I realize we're using a very
Speaker 1: broad brush because when we say improve hormone profiles, what
Speaker 1: are we really talking about? And for me, at least,
Speaker 1: I think about the subjective stuff. You know, do people
Speaker 1: feel like they are going to have more energy as
Speaker 1: a consequence of doing these things? Are they going to
Speaker 1: have the more optimized libido? Or are they going to have
Speaker 1: more optimized recovery from exercise? Right? Because I mean, it's
Speaker 1: not clear to me that taking one's testosterone from six
Speaker 1: hundred to eight hundred is always going to be a
Speaker 1: good thing, especially if estrogen is increasing in parallel. That
Speaker 1: could cause issues. It could certainly make things better, it
Speaker 1: could certainly make things worse.
Speaker 3: Right, Let's briefly mention vitamin D, which is also a hormone.
Speaker 3: It's actually a sterile hormone, and if you have deficient
Speaker 3: vitamin D and you replace it, then you will optimize
Speaker 3: your testosterone. It's also mentioned boron, so if you have
Speaker 3: a very high SHBG, boron can acutely help lower it,
Speaker 3: usually in a dose of five to twelve milligrams per day.
Speaker 3: It's not really a sustained effect, but boron is depleted
Speaker 3: in soils in many countries. I believe it's very high
Speaker 3: in soils in Grease and Turkey, so eating dates or
Speaker 3: raisins that are from those areas potentially have more boron.
Speaker 3: Boron also might be one of the reasons why the
Speaker 3: reference range for testosterone is much higher in those countries
Speaker 3: than other countries.
Speaker 1: And just to remind people that SHBG sex hormone mining
Speaker 1: globulin is attaching to the diesosterone molecule and limiting the
Speaker 1: amount of so called free testosterone that's available to have
Speaker 1: its impact on cells. Okay, so vitamin D three, I'm
Speaker 1: guessing you're talking about vitamin D three specifically when you
Speaker 1: say vitamin D and then boron five to twelve milligrams
Speaker 1: per day, right, and then what are some of the
Speaker 1: other things to optimize testosterone that are in supplement form.
Speaker 3: We can talk about things that affect the steroidogenesis cascades,
Speaker 3: So we could touch on ton cat ali. I know
Speaker 3: we've talked about that a little bit before.
Speaker 1: It and I'm guessing a number of people probably haven't
Speaker 1: heard that conversation.
Speaker 3: Also known as long jack and net upregulates several different
Speaker 3: enzymes in this steroidogenesis cascade and by that what you
Speaker 3: mean if and this is another good thing to google.
Speaker 3: I think anybody interested in a hormone optimization should understand
Speaker 3: where sterole hormones come from. They come usually from cholesterol,
Speaker 3: and they can be shunted off to vitamin D very easily.
Speaker 3: They can be shunted off to testosterone or estrogens or
Speaker 3: progestogens quite easily as well. But tonkat helps with the
Speaker 3: conversion of multiple key steps where you synthesize testosterone another
Speaker 3: I think of it as like a coenzyme or a cofactor.
Speaker 3: An upregulator of these steps is insulin and IGF one.
Speaker 3: So a good rule of thumb is if you are
Speaker 3: not expecting as much growth hormone insulin and IGF one,
Speaker 3: for example, lower carb diets, caloric deficits, you're trying to
Speaker 3: cut body fat or body weight, then toncat is going
Speaker 3: to be theoretically a specially powerful What.
Speaker 1: Sorts of dosages of tongua do you recommend to your patients.
Speaker 3: Anywhere from three hundred to twelve hundred milligrams a day
Speaker 3: with tongkat, you need to be careful with the standardization
Speaker 3: because if you're thinking about a general tonkat supplement, which
Speaker 3: is by far the most well studied. Then you're looking
Speaker 3: at the uryicominone content, which is a plant compound that
Speaker 3: is likely the main active pharmacologic effect. So that's the
Speaker 3: compound that's having the effect on the body. And if
Speaker 3: you standardize the uryicominone very very high, then theoretically you're
Speaker 3: having more effect at a lower dose.
Speaker 1: My blood work tells me that it causes an increase
Speaker 1: in free testosterone for me and also a slight increase
Speaker 1: in lutinizing hormone for me. What are some of the
Speaker 1: other effects on various hormones that you've observed in the
Speaker 1: blood work of your patients?
Speaker 3: Taking tongua ali tongkat can also slightly increase DHA And
Speaker 3: if you have a very high SHBG. Again, that's the
Speaker 3: protein that binds up your androgens, and estrogen's an extremely
Speaker 3: important protein. The higher your SHBG, the more it helps
Speaker 3: decrease it. So they've studied tongkat in populations with very
Speaker 3: normal shbgs and it does nothing for SHBG.
Speaker 1: Interesting, does that mean it does nothing for somebody overall?
Speaker 1: So if somebody has SHBG that's in the normal range,
Speaker 1: will taking tonguat benefit them in any other way.
Speaker 3: Yes, it'll increase their total and free testosterone.
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Speaker 1: ag one subscription. What are some of the other hormones
Speaker 1: that you prescribe to your patients who do not want
Speaker 1: to go on testosterone replacement therapy or take exogens DHA
Speaker 1: or anything like that.
Speaker 3: We could talk about Fidosian next. Fidosia is interesting because
Speaker 3: it's a genus of plants. Fidosia agrestis is one of them.
Speaker 3: There's many others that are very interesting. That species is
Speaker 3: likely the most well studied. And it will increase LH,
Speaker 3: so I would not consider it an LH mimetic, so
Speaker 3: it doesn't really mimic it, but it increases the release
Speaker 3: of lutinizing the hormone from the pituitary. That's a hormone
Speaker 3: that binds to the late E cell, to the LED receptor,
Speaker 3: kind of like HGG does. And it will increase the
Speaker 3: release of testosterone.
Speaker 1: What dosages do you have patients, Steake, I've heard of
Speaker 1: some potential toxicity to the testicular cells.
Speaker 3: There is one study, and this is a rat study,
Speaker 3: but you can equate the dose of toxicity in rats
Speaker 3: in humans. They did not give these rats any antioxidants.
Speaker 3: But it increases a couple different like pro inflammatory markers.
Speaker 3: One is GGT or gamma gluten transfer race comes from
Speaker 3: both the testes and the liver, and one is alkaline
Speaker 3: phosphatase also known as alk FOSS, again coming from both areas.
Speaker 3: There are several different ways that you can attenuate this increase,
Speaker 3: and you can also just check to see if you
Speaker 3: have increased in the rat dose that equates with humans
Speaker 3: that had no effect. So the safe dose was an
Speaker 3: average of three hundred milligrams a day.
Speaker 1: So that would be three hundred milligrams a day in humans.
Speaker 1: Is the dosage that did not have toxicity.
Speaker 3: Correct correct, And often even if there is toxicity in rats,
Speaker 3: there is not toxicity humans, so it's not directly equitable,
Speaker 3: but to be safe, another regimen that I have people
Speaker 3: take is six hundred milligrams every other day or six
Speaker 3: hundred milligrams three times a week, often Monday, Wednesday, Friday.
Speaker 1: My understanding is that nowadays a lot of people are
Speaker 1: using testosterone. Let's not even call it replacement therapy, because
Speaker 1: some of these people have six hundred and seven hundred
Speaker 1: or even you know, eight hundred and agram per deesile
Speaker 1: to read, so replacing anything that is diminished, they're just
Speaker 1: trying to augment what's already there, increase what's already there.
Speaker 2: My understanding is.
Speaker 1: That taking a low dose more frequently is going to
Speaker 1: be more beneficial than the kind of old school way
Speaker 1: of giving you know, one hundred or even two hundred
Speaker 1: milligrams in a single injection once every two weeks.
Speaker 2: Is that right?
Speaker 1: And what do you do with your patients? So let
Speaker 1: me give you a hypothetical. Somebody comes into your office.
Speaker 1: There their blood work and they have blood levels of
Speaker 1: let's say, six hundred anagrants pertest or estosterone. Their estrogen
Speaker 1: is also a normal range. Everything else checks out, but
Speaker 1: they're complaining of, you know, slightly diminished libido, slightly poor
Speaker 1: recovery from workouts, maybe you know, reduce motivation and drive,
Speaker 1: although no major depression. And you come to the conclusion
Speaker 1: that testosterone therapy. Not replacement, but testosterone therapy might be
Speaker 1: a good option to explore. What's a typical dosage range
Speaker 1: and frequency of administration range that you might consider exploring.
Speaker 3: Some of this depends on the SHBG and free testosterone
Speaker 3: as well. So if that same individual had a very
Speaker 3: high SHBG, which again is the binding protein that binds
Speaker 3: up the testosterone and all androgens and estrogens, if it
Speaker 3: is extremely high and they have a free testosterone of two,
Speaker 3: then they might need a different dose because they need
Speaker 3: enough testosterone in order to have a normal uganadol free testosterone.
Speaker 3: But a general normal dosing range, especially for someone starting,
Speaker 3: is around one hundred to one hundred and twenty milligrams
Speaker 3: divided over the course of a week, usually either every
Speaker 3: other day or three times a week, occasionally twice a week.
Speaker 3: Many people with SHBG a bit higher can get away
Speaker 3: pretty easily with twice a week. This is assuming that
Speaker 3: the ester is sipienate or a nantheate, So.
Speaker 1: Two sixty milligram injections of tesosconcipientate per.
Speaker 3: Week, yeah, very common dosing.
Speaker 1: To hit that one hundred and twenty milligrams per week.
Speaker 1: As kind of the typical average.
Speaker 3: Erect and I would consider this like a physiologic yugan adult.
Speaker 3: For many people, even two hundred milligrams a week is
Speaker 3: far above the reference range. All of this is said
Speaker 3: with the caveat that testosterone is normally released in a
Speaker 3: pulsatile manner, so it's high in the morning, low in
Speaker 3: the evening, Whereas if you're on testosterone therapy, then you're
Speaker 3: going to have a steady state, so your testosterone level
Speaker 3: is going to be pretty much the same even in
Speaker 3: the evening.
Speaker 1: In your experience, when patients do that, they I'm guessing
Speaker 1: they report the normal constellation of positive effects, you know,
Speaker 1: improved mood, improved energy, improved sleep, recovery, et cetera. But
Speaker 1: what are some of the hazards or things that can
Speaker 1: crop up in blood work or just subjectively that can
Speaker 1: be warning signs that even a dosage of one hundred
Speaker 1: and twenty milligrams divided into these two or three dosages
Speaker 1: per week is too high.
Speaker 3: So this is when you really have to be at
Speaker 3: least well versed in every organ system, not just the
Speaker 3: ganadal like you know, genital system. You need to do
Speaker 3: have you know, dermatology, prowess, acne is very common change
Speaker 3: lots of different skin pathologies or even bruising can be
Speaker 3: related to hormone replacement. Hair Loss is very common to
Speaker 3: see as well mental status changes. It could occasionally it
Speaker 3: even induces a manic or a bipolar episode because testosterone
Speaker 3: is also dopaminergic and then cardiovascularly, not just in the heart,
Speaker 3: but also concerns for like microvascular a schemic disease, ferretin
Speaker 3: build up because the estrogen also increases, and then fertility
Speaker 3: concerns as well, and lipid concerns too, So you really
Speaker 3: have to be you know, hematologist, dermatologist, cardiologists, lipidologists, the
Speaker 3: whole nine yards.
Speaker 1: So another reason or set of reasons rather to if
Speaker 1: one is considering using testosterone therapy to really do this
Speaker 1: in close communication with a really good physician.
Speaker 2: Because that's a lot to monitor.
Speaker 1: Knowing whether or not you have acting or not is
Speaker 1: one thing, but knowing whether or not your LDL is
Speaker 1: going up, your ApoB is going up, that's a whole
Speaker 1: other biz and that needs to be done through blood
Speaker 1: work is what I'm hearing.
Speaker 3: Correct And if your physician that is managing or prescribing
Speaker 3: your testosterone therapy or your HRT is not well versed
Speaker 3: in these systems, you would want him or her to
Speaker 3: be part of an interdisciplinary team where they have other
Speaker 3: experts that can monitor those systems.
Speaker 1: There are males out there who want to increase their
Speaker 1: testosterone and other hormones, maybe growth hormone, et cetera, who
Speaker 1: opt to not take exogenous testosterones, no cream, no pellet,
Speaker 1: no no pill, no injectable scipion eate, but decide to
Speaker 1: take chlomophin a couple times a week. My understanding, I've
Speaker 1: never done this, I would say if I had. My
Speaker 1: understanding is that taking chlomophin maybe two fifty milligram tablets
Speaker 1: a week is what I hear people are doing, will
Speaker 1: increase what lutinizing hormone, the various estrogen receptor subunits. You
Speaker 1: explain how chomophin would benefit anyone, and is this a
Speaker 1: good strategy. I'm hearing that it's been done quite a
Speaker 1: lot now.
Speaker 3: It will increase testosterone in a dose to pendent manner,
Speaker 3: but it has many other pharmacodynamic effects, which is the
Speaker 3: effect of the drug on the body other than its
Speaker 3: effect on the hypothalamus in the pituitary. So in the
Speaker 3: hypothalamus and the pituitary it does what's called negative feedback inhibition,
Speaker 3: or it blocks the axgen of estrogen, so it crowds
Speaker 3: out estrogen from the estrogen receptor on the hypothalamus and
Speaker 3: the pituitary.
Speaker 1: Why would I want to take something that would increase
Speaker 1: the activity of an estrogen receptor.
Speaker 2: I just can't find the rationale for that.
Speaker 3: The main rationale behind taking a serm is as a
Speaker 3: very temporary measure that is not going to suppress pituitary
Speaker 3: or hypothalmic function. If your testosterone is just so drastically
Speaker 3: low that it is unlikely to recover anyone anyway. So
Speaker 3: most of the time it is not clinically useful and
Speaker 3: SERMs should not be prescribed very often, certainly not as
Speaker 3: long term testosterone replacement or testosterone optimization in most individuals.
Speaker 3: There's always exceptions to everything. But there's five different estrogen
Speaker 3: and estrogen related receptors. There's two main estrogen receptors and chlomid,
Speaker 3: and every serm has a very unique profile because they
Speaker 3: selectively inhibit some receptors in some tissues but not other
Speaker 3: receptors and other tissues. For example, Chlomid can inhibit receptors
Speaker 3: that are in the eye, and it can cause visual
Speaker 3: changes blurry vision, especially at higher doses, and it also
Speaker 3: acts in every other tissue with the body, so side
Speaker 3: effects from chlomid and other selective estrogen receptor modifiers are
Speaker 3: very common.
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Speaker 2: Alcohol.
Speaker 1: Does it increase a romatase the enzi on the converse
Speaker 1: distosterone into estrogen or not?
Speaker 2: And is there a dose dependence there?
Speaker 3: It significantly? Does there is a dose dependence? In general,
Speaker 3: I would not recommend more than three to four, you know,
Speaker 3: standard drinks. One huge glass of wine is probably five
Speaker 3: standard drinks every two weeks. The other thing to keep
Speaker 3: in mind with alcohol is as a lot of calories
Speaker 3: seven kilo calories program almost as much as fat, which
Speaker 3: is nine. And then it's also very gaba urgic, so
Speaker 3: it can activate inhibitory neurotransmission, and that can also affect
Speaker 3: how many how much LH and H is released, so
Speaker 3: that can also decrease testosterone, almost kind of similar to
Speaker 3: how opiates can decrease testosterone.
Speaker 1: I want to go back to the prostate and talk
Speaker 1: to you about something that's kind of a newer emerging trend.
Speaker 1: I know that you've talked to a little bit about
Speaker 1: this in previous podcasts that a number of men, I
Speaker 1: should say a number of physicians are prescribing low dose
Speaker 1: to dalophil also known as cialis, to their male patients,
Speaker 1: so in dosage ranges of like two point five milligrams
Speaker 1: to five milligrams per day, but not for a rectile dysfunction,
Speaker 1: but rather for improving prostate health, and presumably they get
Speaker 1: sort of a boost in terms of blood flow to
Speaker 1: the genitalia as well, but again not specifically a deal
Speaker 1: with a rectile dysfunction, but to deal with prostate health
Speaker 1: and blood flow to the prostate. Is that something that
Speaker 1: you sometimes often prescribe to your patients, and of what age.
Speaker 3: Toda alifil is a very underrated medication. The age would
Speaker 3: kind of depend on the indication, so ted aaliphil is
Speaker 3: also a blood pressure medication. It can very slightly decrease
Speaker 3: blood pressure, especially at higher doses. At higher doses at
Speaker 3: theorem a high dose would be twenty miligrams, not two
Speaker 3: point five milligrams, but consistently it can somewhat affect with
Speaker 3: the cones in the eye that have to do with
Speaker 3: red and green sight, although if you remove it, that
Speaker 3: effect is reversed. So basically, if you don't need really
Speaker 3: really good red green discrimination, you can take higher doses,
Speaker 3: but in general I recommend no higher than ten milligrams
Speaker 3: a day, usually just two or five miligrams. One other
Speaker 3: benefit or other use of tadalophil is that it increases
Speaker 3: the density of the androgen receptor, similarly to L carnotine,
Speaker 3: so that's an interesting benefit. Another benefit is that if
Speaker 3: you give it to people with nocturia, which is urinating
Speaker 3: at night, in general, it will cut the episodes in half,
Speaker 3: so it could go from two to one, which can
Speaker 3: make a big difference for your sleep, which will secondarily
Speaker 3: make a big difference for your growth. Hormone into stosterone optimization.
Speaker 1: Interesting, So you said two point five to five milligrams
Speaker 1: per day is kind of typical for these prostate enhancing effects.
Speaker 2: Yes, I get a.
Speaker 1: Lot of questions about drugs to offset hair loss. Most
Speaker 1: of those drugs are going to operate through the DHD system,
Speaker 1: the DEHYDRAGSI stosterone system for the reasons we talked about before,
Speaker 1: DHG receptors being on the scalp and causing beard growth
Speaker 1: on the face. Is it the case that a number
Speaker 1: of people taking things like Propecia and other things to
Speaker 1: block the DHT or disrupt the DHT pathway are going
Speaker 1: to experience diminished sex drive, diminished you know, kind of
Speaker 1: motivation and general vigor. And if so, are there alternatives
Speaker 1: like topical DHD antagonists that they might use if they
Speaker 1: want to keep their hair but not have those negative effects.
Speaker 3: Many people that have just a bit of predisposition, they
Speaker 3: can use things that are topical anti androgens. Ketoconazola is
Speaker 3: one of them. Caffeine is actually another one.
Speaker 1: Wait, you have to explain how this works. How do
Speaker 1: people get caffeine into the hair of ollicle?
Speaker 3: Topically, the caffeine enters the scalp and crowds out like
Speaker 3: somewhat crowds out the androgen. It is a weak effect.
Speaker 3: It's likely just strong enough to be clinically significant. Usually
Speaker 3: caffeine is put into formulations with other things like ketoconazol
Speaker 3: that are also weak anti androgens. Of notes, spronlactone can
Speaker 3: be prescribed topically, but it is absorbed systemically because the
Speaker 3: size of the molecule, So unless your doctor specifically prescribes
Speaker 3: that for you, especially as a male, do not use
Speaker 3: topical spronalactone. Topical finasteride is also a smaller molecule, so
Speaker 3: it is also systemically absorbed, but it is not extremely
Speaker 3: well systemically absorbed. If you take topical phinasteride, then usually
Speaker 3: your systemic DHT will decrease by about thirty percent. Topical
Speaker 3: detasteride is likely a tiny bit systemically absorbed, but it's
Speaker 3: unique because it's half life is much faster at a
Speaker 3: lower dose, So topical do testeride will not affect your
Speaker 3: systemic DHD at all, And I've seen this anecdotally on
Speaker 3: many people on topical do testeride therapy.
Speaker 1: On behalf of the audience and just for myself, Thank
Speaker 1: you so much, you have an immense amount of knowledge
Speaker 1: and you're exquisitely good at sharing it with people in
Speaker 1: an actual way, So thank you, my pleasure,