Welcome to Hubberman Lab Essentials,
where we revisit past episodes for the
most potent and actionable science-based
tools for mental health, physical
health, and performance.
I'm Andrew Huberman, and I'm a professor
of neurobiology and opthalmology at
Stamford School of Medicine. And now for
my discussion with Dr. Kyle Gillette.
Dr. Gillette, great to have you back.
>> Great to be back. Thank you. I'd like to
begin with a question about what all
males ought to do in order to optimize
their hormones. What should they be
doing? What should they avoid doing if
the goal is to have a long arc of
healthy hormone optimization throughout
the lifespan? There's many things that
you should do. An analogy that I often
make is when there's a brand new car
that comes off the assembly line, you do
a full scope of diagnostic workup, hook
it up to the computer. And I think we
should do the same thing with humans as
well. during puberty, you know,
obviously you're a functioning human,
but uh I would say there's still
development and I think that the the
human always develops. I don't think
development ever ends, but you want to
monitor that progress across a person's
lifespan.
>> What do you think are the key things to
look for in blood work? I mean,
testosterone is always the topic that
comes up in the context of male hormone
optimization, but certainly there are a
lot of other hormones that are important
as well. Mhm. And with testosterone, you
want to get either testosterone and SHBG
or a free testosterone.
>> Could you define SHBG for our listeners,
please?
>> It is sex hormone binding globbulin. It
is the protein that binds up all
androgens and estrogens in the body. So
the stronger the androgen, the stronger
it binds. During puberty, strong
androgens, especially DHT, which is the
strongest bio identical androgen, has a
huge role, a prominent role in secondary
sexual characteristics. And if your SHBG
is very high, then your DHT can run
higher because it's not metabolized, but
there's not quite as much free DHT. So,
you want to balance between um a high
enough free DHT and a high enough total
DHT. So assuming that there's no major
intervention, how often do you recommend
that people get their blood work done
>> using shared decision-m with their
physician, usually a good follow-up is
about 6 months.
>> So on a daily basis, uh maybe you could
just take us through the arc of a day
and um and push out some of the
protocols that you use or the things
that you like to see your male patients
use in order to try and optimize their
hormone status.
>> I'll briefly touch on some of the
lifestyle pillars to start. Diet and
exercise are the first two. Um, in
puberty, sleep is particularly
important, of course. Um, but with diet
and exercise, um, throughout a lifespan,
you want to not exclude things that are
helping you. For example, during
puberty, if you're consuming dairy and
then all of a sudden you cut out all
dairy, dairy can help increase IGF-1 and
free IGF-1. And and just uh again for
our audience maybe you just mentioned
what IG what having enough IGF-1 can do
for us that's beneficial is
>> it helps you grow it helps with u
genital development secondary sexual
characteristics and long bone growth um
skin growth hair growth a host of things
>> so getting an array of nutrients that
include dairy what other sorts of
nutrients are important during
development
>> you want to have adequate vitamin D
vitamin D helps with testosterone
production helps again with bone
mineraliz ization and stature. Um, after
an age of about 25, and there's not a
strict cut off, but up to about an age
of 25, optimizing your growth hormone
and IGF-1 helps with bone density and
bone growth. So, uh, from the dietary
standpoint, you want to have enough free
estrogen. Not too much when you're
growing, but you want to help, um,
basically stockpile bone to prevent a
risk of osteoporosis or thin bones,
fractures when you're older. I realize
that some of this relates to ethics and
food allergies and things of that sort,
but would you say that on balance that
most people would benefit from eating a
combination of, you know, quality
proteins from animal sources and
non-animal sources, fruits, vegetables,
and starches? I mean, what do you think
for instance about people following a
pure carnivore or a very uh pure vegan
diet in their 20s and 30s?
>> In their late 20s, it might be a
reasonable option. In early 20s and
certainly teens, it is a horrible idea
because it is likely to significantly
decrease your free androgens. So, you
will have less testosterone acting on
receptors through the body.
>> Are there any other micronutrients or
macronutrients that people in their 20s
and 30s should emphasize?
>> Fiber is going to be paramount in kind
of like setting your set point of your
gut microbiome the rest of your life.
There is prebiotic fiber, which you can
think of as fish food for your good gut
microbiome. Your gut microbiome is kind
of like an aquarium or a fish tank. Any
fiber or food that you're putting in
your gut, it's either going to it's
going to skew your gut microbiome
towards something that is more
beneficial or or more detrimental.
>> And would you say that the prebiotic
fiber and the getting essential fatty
acids that would be important to do
throughout the lifespan or just for
people in their 20s and 30s? throughout
the lifespan. Um, particularly important
in the teenage, 20s, 30s because it
helps with brain development. Um, you're
certainly more of an expert than me when
it comes to um, brain development, but
it does continue to de develop through
really throughout the lifespan, but
certainly through the 20s and 30s as
well. In a previous discussion of ours,
I asked you about um, caloric
restriction and testosterone. And if I
recall correctly, the idea was that if
somebody is overweight, they have excess
fat atapost tissue, then getting rid of
some of that atapost tissue by through
caloric restriction and exercise,
provided it's done not too fast in a
healthy way, is going to be beneficial
for testosterone in the long run. But
that for individuals who are not
carrying an excess of body fat, caloric
restriction is actually going to lower
testosterone.
First of all, do I have that correct?
And second, are there any um addendums
to that that you'd like to to give us
now?
>> That's correct. Um if you look at an
individual in a caloric deficit, several
changes will happen. One is that they'll
have less building blocks for hormones.
Another is that they will be in a
catabolic state more often. So that
balance of anabolism and cat catabolism
will be different. They'll likely have
less signaling from growth hormone and
IGF-1. And they'll also have the high
SHBG that we defined earlier as the
binding protein. So their free androgens
and free estrogens will go down.
>> Now what are some of the other pillars
of creating the proper environment for
hormone optimization?
>> Uh stress is probably the next one. um
during uh both puberty but also the 20s
and 30s individuals are figuring out how
they want to cope with stress and also
figuring out what they want to choose to
put their effort into.
So if someone is overstressed then it
can have uh it can put all the other
lifestyle pillars and then they stop
dieting well um they stop exercising and
everything else can go a skew. What
would the be some of the additional
things that everybody should do?
>> Another one is finding what your purpose
is in life. So, I call this spirit, but
it's really just the self-actualization
component of Maslo's hierarchy of needs,
which is basically your physical needs,
your mental needs, and then your purpose
in life, what you really like to do. The
idea is not to pick the end goal, is to
pick a goal, and then once you reach
that goal to assess and then pick
another goal and so on. I think
sometimes when people hear about picking
a purpose, they're like, "Oh my
goodness, I have to define sort of like
naming oneself that you you you actually
can change your your your goals and
purpose over time." I'd like to return
to the key things that people should do
or I should say the key things that men
should do to optimize their hormones.
What do you think is a healthy
sustainable exercise regimen that anyone
can follow that will also support their
hormone status?
>> For really vigorous exercise around 3 to
four times a week is very sustainable
over a long period of time. On top of
that, you could add in three or four
more instances of less vigorous
exercise. when they study the effect of
exercise, specifically vigorous
exercise. Um, one area that's been
studied is uh vigorous exercise episodes
lasting longer than an hour. And they
usually track it by a rating of
perceived exertion, which isn't perfect
and it's not extremely actionable, but
it's helpful for clinical science. But
the takeaway from that is basically do
not it is not hormonally helpful to
train especially regularly train uh
vigorously for longer than an hour.
These days for better or for worse I
think for worse younger guys are asking
about and using testosterone replacement
therapy so-called TRT. Why in the world
would any male in his teens or 20s or
even 30s whose blood levels of
testosterone and estrogen are at the
appropriate levels, I mean within the
normal reference range? Why would they
you take exogenous testosterone
given all the negative effects on
fertility um some of the challenges that
it can present if the dosages aren't
quite right etc. Why would they do that?
Certainly, if they are not being paid
for a particular endeavor, like they're
not making money. If they are playing a
sport, chances are they're not allowed
to do that anyway. It's it's on the
bannes list. So, to me, it just seems
like a crazy idea. Um, but then again,
I'm of a generation that really hasn't
thought about doing that stuff until
people were in their 40s and 50s or even
never. So is there ever a case for
somebody in their 20s or 30s to take
testosterone espe if their blood levels
are within the 300 to 900 nanogs per
deciliter reference range. You know
everyone has their different reason uh
as far as like when does the benefit
outweigh the detriment. Not very often
if you're um in your 20s and certainly u
probably almost hardly never. There's
always, you know, rare cases like
Coleman syndrome and whatnot, but um
almost never if you're very young.
>> Okay. So, for people in their 20s, 30s
and beyond, 40s, etc. whose testosterone
and estrogen levels are at the
appropriate ratios and in the within the
normal reference range, uh libido,
energy, recovery, etc. are feeling, you
know, at least um workable for for their
lifestyle. For those people, what can
they do besides get great sleep, train,
but not too hard or too often, etc.,
etc. What are some of the things in the
realm of supplementation that can help
them optimize their testosterone and
estrogen without suppressing their own
endogenous production of testosterone
and estrogen? Let's mention creatine as
the first one. Creatine is interesting
because it has multiple different
effects. It helps with amino acid
synthesis. It also helps with oxidative
stress. It can also serve as the backup
fuel tank for your mitochondria. So,
kind of holding backup ATP and it does
slightly increase total testosterone.
And it also increases the conversion of
testosterone to dihydrotestosterone.
So, potentially it's especially useful
in um men in their even their teenage
years and their 20s. You mentioned the
conversion of testosterone to
dihydrotestosterone and there is
mythology out there that creatine can
increase hair loss. I'm guessing because
there's at least one study showing that
creatine can increase DHT.
Dihydrotestosterone and DHT is one of
the primary hormones that can promote
male pattern baldness. Uh so the
question therefore is does cre creatine
supplementation
increase the rate of hair loss
>> in each individual?
Uh preventing hair loss is a very poor
reason to take creatine because it's not
going to take you to a supra physiologic
level. It's not going to uh you know
increase your androgens to an unnormal
level of binding.
So I feel like um this if that was a
reason to not take creatine for hair
loss then
>> you mean for sorry you mean hair loss is
not a reason to avoid taking creatine.
>> Correct. Hair loss is not a reason to
avoid taking creatine. Um it think of it
as just bringing you to what you are um
naturally inclined to have. If your
conversion of testosterone to DHT is
already high then often creatine does
not affect this. It just kind of resets
your balance between testosterone being
aromatized to estrogen or being five
alpha reduced DHT. So it's not going to
speed up hair loss more than um just
naturally being a male does. So in some
individuals it will have no effect. In
some individuals for whatever reason
they have almost no five alpha reductase
activity, it will return them to natural
or normal.
>> Uh so what other supplement-based tools
uh can people consider? Another one we
can loop in with creatine is betaine.
Some people are non-responders to
creatine. So you can increase that to 10
grams or you can use its cousin betaene
to help with amino acid synthesis and
shunting of energy. Along with that, I
would put Lcarnitine.
>> Betaine. Uh do you recall uh what dosage
people typically would take if they're I
creatine nonresponder?
>> One to three grams. In fact, yeah,
several versions of creatine have
betaine mixed in because it helps with
the processing of methionine and
homocyine.
>> So, if somebody is already taking
creatine and likes it in response to it,
I'll raise my hand such as myself, would
adding betaine help or is it redundant
with creatine?
>> Only if their homocyine is persistently
elevated. And homoyine is kind of like
an inflammatory marker that can build up
if you're not converting enough of it
downstream.
>> How would I know? just a blood test.
>> So, Lcarnitine, uh, what are the ways to
take Lcarnitine? I know that there's an
oral form, so capsules, and there's
injectables. The injectables, I think
you need a prescription. Is that right?
>> Correct. You need a prescription for the
injectables or you should really get a
prescription for the injectables
for when you inject it. Um, of course,
at the supervision of your doctor, it's
usually done intramuscularly. It's an
aquous solution, so it does not have
like an oil or a carrier oil in it like
TR like testosterone esters do. Um,
however, if you inject it too
superficially, it's not going to make or
break anything. Often it just burns if
you inject it subcutaneously and it does
not um disseminate throughout the body
as well. Lcarnitine potentially has
localized effects if you inject it. If
you ingest it orally then it has a very
low bioavailability maybe only 10%.
>> So what are the dosages of Lcarnitine
that one needs to ingest then if they
want to get a benefit because if only
10% is being absorbed uh it's probably a
lot of Lcarnitine. How much should
people take per day?
>> Usually I recommend uh for oral
Lcarnitine between 1,000 milligs and up
to four or 5,000 millig.
>> So one to four maybe even five grams.
>> Correct. up to 5 g a day. If you're on
that much, especially if you have a
disregulated gut microbiome, you should
be concerned with TMAO, which is a
potential carcinogen that both carnitine
and choline can convert into and your
gut microbiota determine how much that
happens.
>> Is it true that I can offset any
negative effects of alpha GPC uh choline
that is NLC carnitine um that I take by
ingesting garlic? Is that right? There's
a compound in garlic called allisonin. I
believe it's a l l i c i n. It's also
part of the scientific name, the genus
of types of garlic. And this can help
decrease the conversion to TMAO.
Bourberine actually slightly decreases
the conversion to TMAO as well. Um
probably through alteration of the gut
microbiome. And then just um optimizing
your gut microbiome can decrease
conversion. So not everyone needs
allisonin, but it's something that you
should certainly consider if you are on
a high dose.
I'm going to continue to take the 600
milligrams of garlic every time I take
my Lcarnitine, but I'm going to skip the
bourberine because bourberine gives me
brutal headaches and it makes me crave
carbohydrates because it drops my blood
sugar.
>> It has many other effects including the
dawn phenomenon where it drops your
blood sugar when you're sleeping and you
can't even realize it.
>> Okay. And what we did not talk about is
what Lcarnitine does.
>> It's a shuttle. So I think it's named
carnitine palmatil co-enzyme A.
Basically, it's it just takes nutrients
from outside your mitochondria and puts
them in. It also has a unique effect.
Well, not too unique because tedalaphil
actually has this effect as well, is
that it increases the density of the
androgen receptor in the cytoplasm of
your cells. So, even if your androgen
receptor sensitivity doesn't change and
even if your testosterone does not
change, you will have more testosterone
binding to that increased number of
receptors. Does one need to cycle
Lcarnitine, creatine, betaine?
>> No reason to cycle any of those. What
other supplements can one use to try and
improve hormone profiles? And and here I
realize we're using a very broad brush
because when we say improve hormone
profiles, what are we really talking
about? And for me at least, I I think
about the subjective um stuff. You know,
do people feel like they are going to
have more energy as a consequence of
doing these things? Are they going to
have the more optimized libido? Are they
going to have more optimized uh recovery
from exercise? Right? Because I mean,
it's not clear to me that taking one's
testosterone from 600 to 800 is always
going to be a good thing, especially if
estrogen is increasing in parallel. That
could cause issues. It could certainly
make things better. It could certainly
make things worse, right? Let's briefly
mention vitamin D, which is also a
hormone. It's actually a sterile
hormone. and have if you have deficient
vitamin D and you replace it, then you
will optimize your testosterone.
Let's also mention boron. So if you have
a very high SHBG, boron can acutely help
lower it, usually in a dose of 5 to 12
milligrams per day. It's not really a
sustained effect, but uh boron is
depleted in soils in many countries. I
believe it's very high in soils in
Greece and Turkey. So eating dates or
raisins that are from those areas
potentially have more boron. Boron also
meet might be one of the reasons why the
reference range for testosterone is much
higher in those countries than other
countries. And just to remind people,
the SHPG sex hormone binding globbulin
is attaching to the testosterone
molecule and limiting the amount of
so-called free testosterone that's
available to have its impact on cells.
Okay. So, vitamin D3, I'm guessing
you're talking about vitamin D3
specifically when you say vitamin D. And
then boron, 5 to 12 milligrams per day,
right? Um, and then what are some of the
other things to optimize uh testosterone
that are in supplement form?
>> We can talk about things that affect the
steroidenesis cascade. So, we could
touch on tonad ali. I know we've talked
about that a little bit before. It's
>> Yeah, but I'm guessing a number of
people probably haven't heard that
conversation.
>> Also known as longjack and that
upregulates several different enzymes in
the steroidenesis cascade. And by that
um what you mean if and this is another
good thing to Google. I think anybody
interested in hormone optimization
should understand where where sterile
hormones come from. They come usually
from cholesterol and they can be shunted
off to vitamin D very easily. They can
be shunted off to testosterone or
estrogens or progesterrogens quite
easily as well. But Tonat helps with the
conversion of multiple key steps where
you synthesize testosterone.
Another um think of it as like a
co-enzyme or a co-actor, an upregulator
of these steps is insulin and IGF-1.
So a good rule of thumb is if you're not
expecting as much growth hormone insulin
and IGF-1, for example, lower carb
diets, caloric deficits, you're trying
to cut body fat or body weight, then
tonat is going to be theoretically
especially powerful.
What sorts of dosages of Tongut do you
recommend to your patients?
>> Anywhere from 300 to,200 milligrams a
day. With Tongat, you need to be careful
with the standardization
because and if you're thinking about a
general Tonat supplement, which is by
far the most wellstudied, then um you're
looking at the uricomone content, which
is a plant compound that is likely the
main um active pharmacologic effect. So
that's the compound that's having the
effect on the body. And if you
standardize the uricomone very very
high, then theoretically you're having
more effect at a lower dose. My blood
work tells me that it causes an increase
in free testosterone for me and also a
slight increase in luteinizing hormone
for me. Um what are some of the other
effects on various hormones that you've
observed in the blood work of your
patients taking Tonga Ali? Tongat can
also slightly increase DHEA.
And if you have a very high SHBG, again,
that's the protein that binds up your
androgens and estrogens, an extremely
important protein. Uh the higher your
SHBG, the more it helps decrease it. So,
they've studied tonat in uh populations
with very normal SHBGs, and it does
nothing for SHBG.
>> Interesting. Does that mean it does
nothing for somebody overall? So if
somebody has SHBG that's in the normal
range, will taking Tongut benefit them
in any other way?
>> Yes, it it'll increase their total and
free testosterone.
>> What are some of the other hormones that
you uh prescribe to your patients uh who
do not want to go on testosterone
replacement therapy or take exogenous
DHEA or anything like that?
>> We could talk about Fidosia next. Uh
Fidosia is interesting because it's a
genus of plants. Fidosia is one of them.
There's many others that are very
interesting. Um, that species is likely
the most wellstied and it will increase
LH. So, um,
>> I would not consider it an LH mimetic.
So, it doesn't really mimic it, but it
increases the release of luteinizing
hormone from the pituitary. That's a
hormone that binds to the latic cell to
the LH receptor kind of like hCG does,
and it will increase the release of
testosterone.
>> What dosages uh, do you have patients
take? I've heard of uh some potential
toxicity to the testicular cells.
>> There was one study and this is a rat
study but you can equate the dose of
toxicity in rats in humans. They did not
give these rats any antioxidants but it
increases a couple different um like
pro-inflammatory markers. One is GGGT or
gamlutamal transferase comes from both
the testes and the liver and one is
alkaline phosphatase also known as alkos
again coming from both areas. There are
several different ways that you can
attenuate this increase and you can also
just check to see if you have increased
in the rat dose that equates with humans
that had no effect. So the safe dose was
an average of 300 mg a day.
>> So that would be 300 milligrams a day in
humans is the dosage that did not have
toxicity. Correct.
>> Correct. And often even if there is
toxicity in rats, there is not toxicity
in humans. So it's not directly
equitable. But to be safe, um, another
regimen that I have people take is 600
milligrams every other day or 600
milligrams three times a week, often
Monday, Wednesday, Friday. My
understanding is that nowadays a lot of
people are using testosterone. Let's not
even call it replacement therapy because
some of these people have 600, 700 or
even, you know, 800 nog per deciliter
read. So they're not replacing anything
that is diminished. They're just trying
to augment what's already there,
increase what's already there. My
understanding is that taking a low dose
more frequently is going to be more
beneficial than the kind of old school
way of giving, you know, 100 or even 200
milligrams in a single injection once
every two weeks. Is that right? And and
what do you do with your patients? So,
let me give you a hypothetical. Somebody
comes into your office, they um do their
blood work and they have um blood levels
of let's say 600 NOGS per deciliter
testosterone. Their estrogen is also in
normal range. everything else checks
out, but they're complaining of, you
know, slightly diminished libido,
slightly poor recovery from workouts,
maybe um, you know, reduced motivation
and drive, although no major depression,
and you come to the conclusion that
testosterone therapy, not replacement,
but testosterone therapy might be a good
option to explore. What's a typical
dosage uh, range and frequency of
administration range that you might
consider exploring? And
>> some of this depends on the SHBG and
free testosterone as well. So if that
same individual had a very high SHBG,
which again is the binding protein that
binds up the testosterone and all
androgens and estrogens, if it is
extremely high and they have a free
testosterone of two, then they might
need a different dose because they need
enough testosterone in order to um have
a normal yugenatal free testosterone.
But a general normal dosing range,
especially for someone starting, is
around 100 to 120 milligrams divided
over the course of a week. Usually
either every other day or three times a
week, occasionally twice a week. Many
people with SHBG a bit higher can get
away pretty easily with twice a week.
This is assuming that the esther is
cipionate or ananthate.
>> So two 60 mgram injections of
testosterone cipionate per week.
>> Yeah. very common dosing
>> to hit that 120 milligs per week as kind
of the typical average.
>> Correct.
>> And I would consider this um like a
physiologic yugenatal dose. For many
people, even 200 milligrams a week is
far above the reference range. All of
this is said with the caveat that
testosterone is normally released in a
pulsatile manner. So it's high in the
morning, low in the evening. Whereas if
you're on uh testosterone therapy, then
um you're going to have a steady state.
So your testosterone level is going to
be pretty much the same even in the
evening.
>> In your experience, when patients do
that, they I'm guessing they report the
normal constellation of positive
effects, you know, improved mood,
improved energy, improved sleep,
recovery, etc. What are some of the
hazards or things that um can crop up in
blood work or just subjectively that um
can be warning signs that even a dosage
of 120 milligrams divided into these two
or three dosages per week is too high.
So this is when you really have to be uh
at least well-versed in every organ
system, not just the gonatal um like you
know genital system. You need to have uh
you know dermatology prowess. Acne is a
very common change. Lots of different uh
skin pathologies or even bruising can be
related to hormone replacement. Hair
loss is very common to see as well. Um
mental status changes. It could in
occasionally it even induces a manic or
a bipolar episode because testosterone
is also dopamineergic.
And then cardiovascularly not just in
the heart but also concerns for like
microvascular eskeemic disease, feritin
buildup because the estrogen also
increases and then uh fertility concerns
as well and lipid concerns too. So you
really have to be you know hematologist,
dermatologist, cardiologist, um
lipidologist, the whole nine yards. So,
another reason or set of reasons rather
to uh if one is considering using
testosterone therapy to really do this
in close communication with a really
good physician because that's a lot to
monitor. Knowing whether or not you have
acne or not is one thing, but knowing
whether or not your LDL is going up,
your APOB is going up, that's a whole
other biz and that needs to be done
through blood work is what I'm hearing.
>> Correct. And if your physician that is
managing or prescribing your uh
testosterone therapy or your HRT is not
well verssed in these systems, you would
want him or her to be part of an
interdisciplinary team where they have
other experts that can monitor those
systems. There are males out there who
want to increase their testosterone and
other hormones, maybe growth hormone,
etc. who opt to not take exogenous
testosterone. So, no cream, no pellet,
no no um pill, no injectable cpionate,
but decide to take Clomophin a couple
times a week.
My understanding, I've never done this,
I would say if I had. My understanding
is that taking Clomophin maybe 2 50
milligram tablets a week is what I hear
people are doing, will increase what
luteinizing hormone,
the various estrogen receptor subunits.
Could you explain how Clomophin would
benefit anyone and is this a good
strategy? I'm I'm hearing that it's
being done quite a lot now.
>> It will increase testosterone in a dose
dependent manner, but it has many other
pharmacodnamic effects which is the
effect of the drug on the body other
than its effect on the hypothalamus and
the pituitary. So in the hypothalamus
and the pituitary, it uh does what's
called negative feedback inhibition um
or it it blocks the oxygen of estrogen.
So it crowds out estrogen from the
estrogen receptor on the hypothalamus
and the pituitary.
>> Why would I want to take something that
would increase the activity of an
estrogen receptor? I just can't find the
rationale for that.
>> The main rationale behind taking a ser
is as a very temporary measure that is
not going to suppress pituitary or
hypothalammic function. if your
testosterone is just so drastically low
that it is unlikely to recover anyway.
So most of the time it is not clinically
useful and um serum should not be
prescribed very often. Certainly not as
long-term testosterone replacement um or
testosterone optimization in most
individuals. There's always exceptions
to everything, but um there's five
different estrogen and estrogen related
receptors. There's two main estrogen
receptors in Clomid and every serm has a
very unique profile because they
selectively inhibit some receptors in
some tissues but not other receptors in
other tissues. For example, um Clomid
can inhibit receptors that are in the
eye and it can cause um visual changes,
blurry vision um especially at higher
doses and it also acts in every other
tissue of the body. So side effects from
Clomid and other selective estrogen
receptor modifiers are very common.
>> Alcohol, does it increase aromatase, the
enzyme that converts testosterone into
estrogen or not? And um is there a dose
dependence there?
>> It significantly does. There is a dose
dependence. In general, I would not
recommend more than uh three to four,
you know, standard drinks. uh one huge
glass of wine is probably five standard
drinks every two weeks. The other thing
to keep in mind with alcohol is it has a
lot of calories, 7 kilo calories per
gram, almost as much as fat, which is
nine. And then it's also very gabaurgic.
So it it can activate inhibitory
neurotransmission. Um and that can also
affect how many how much uh LH and FSH
is released. So that can also decrease
testosterone almost kind of uh similar
to how opiates can decrease
testosterone. I want to go back to the
prostate and talk to you about something
that's kind of a newer emerging trend. I
know that um you've talked a little bit
about this in uh previous podcasts that
a number of men or I should say a number
of physicians are prescribing lowdosese
talopil also known as seialis to their
male patients. So in dosage ranges of
like 2.5 milligrams to 5 milligrams per
day, but not for erectile dysfunction,
but rather for improving prostate health
and presumably they get sort of a boost
in terms of blood flow um to the
genitalia as well. But again, not
specifically to deal with uh erectile
dysfunction, but to deal with prostate
health and blood flow to the prostate.
Is that something that you sometimes
often prescribe to your patients? And of
what age?
>> Tedal is a very underrated medication.
Um the age would kind of depend on the
indication.
So tadalaphil is also a blood pressure
medication. It can very slightly
decrease blood pressure especially at
higher doses. At higher doses it theor a
high dose would be 20 milligrams not 2.5
milligrams but consistently it can
somewhat affect with the cones in the
eye that have to do with red and green
sight. Although if you remove it that
effect is reversed. So basically if you
don't need really really good red green
discrimination you can take higher doses
but in general I recommend no higher
than 10 milligs a day usually just two
or 5 milligs.
One uh other benefit or other use of
tadalapil is that it increases the
density of the androgen receptor
similarly to lcarnitine.
So that's an interesting benefit.
Another benefit is that if you give it
to people with nocturia, which is
urinating at night in general, it will
cut the episodes in half. So it could go
from two to one, which can make a big
difference for your sleep, which will
secondarily make a big difference for
your growth hormone and testosterone
optimization.
>> Interesting. So you said 2.5 to 5
milligrams per day is kind of typical
for these prostate enhancing effects.
>> Yes. I get a lot of questions about
drugs to offset hair loss. Most of those
drugs are going to operate through the
DHT system, the dihydrotestosterone
system, for the reasons we talked about
before, DHT receptors being on the scalp
and causing beard growth on the face. Is
it the case that a number of people
taking um things like Propecia and other
things to block the DHT or disrupt the
DHT pathway are going to experience
diminished um sex drive, diminished um
you know, kind of motivation and general
vigor? And if so, are there alternatives
like topical DHT antagonists that they
might use um if they want to keep their
hair but not have those negative
effects?
>> Many people that have just a bit of
predisposition, they can use things that
are topical anti-androgens.
Uh ketoconazol is one of them. Caffeine
is actually another one.
>> Wait, you have to explain how this
works. How do people get caffeine into
the hair follicle? Topically, the
caffeine enters the scalp and crowds out
like somewhat crowds out the androgen.
It is a weak effect. It's likely just
strong enough to be clinically
significant. Usually, caffeine is put
into formulations with other things like
ketoconol that are also weak
anti-androgens. Of notes, spironolactone
can be prescribed topically, but is it
is absorbed systemically because the
size of the molecule. So unless your
doctor specifically prescribes that for
you, especially as a male, do not use
topical spironolactone.
Topical finasteride is also a smaller
molecule. So it is also systemically
absorbed, but it is not extremely well
systemically absorbed. If you take
topical finasteride, then usually your
systemic DHT will decrease by about 30%.
Topical dutasteride is likely a tiny bit
systemically absorbed, but it's unique
because its half-life is much faster at
a lower dose. So topical dutasteride
will not affect your systemic DHT at
all. And I've seen this anecdotally on
many people on topical dutasteride
therapy. On behalf of the audience and
and just for myself, thank you so much.
You have an immense amount of knowledge
and you're exquisitly good at sharing it
with people in an actionable way. So
thank you.
>> My pleasure.