64__transcript.txt

- Welcome to the Huberman Lab Podcast,
where we discuss science
and science-based tools
for everyday life.
[lively music]
I'm Andrew Huberman.
And I'm a professor of
neurobiology and ophthalmology
at Stanford School of Medicine.
Today my guest is Dr. Kyle Gillett.
Dr. Gillett is dual
board-certified in family medicine
and obesity medicine and practices out
of a clinic in Kansas
and via telemedicine.
He provides full-spectrum medicine,
including hormone health,
preventative medicine, obstetrics,
which is the branch of
medicine and surgery concerned
with childbirth and the care
of women giving birth and pediatrics.
I first learned about Dr.
Gillett from a podcast
of all things and was immediately struck
by the breadth and depth of his knowledge
on all things hormones
and hormone optimization.
As you'll see very soon today,
Dr. Gillett can teach you how
to optimize your hormones
using behavioral tools,
nutrition, exercise-based tools,
supplementation, and hormone therapies
if those are appropriate for you.
There are many professionals out there
including many medical doctors of course,
talking about hormone health.
What really sets Dr.
Gillett apart from the pack
is his ability to understand
how the different factors
that I described before, nutrition,
supplementation, exercise,
and hormone therapies,
how those interact with
one another and the safest
and most rational ways
to approach hormone optimization.
During today's episode,
you will learn how to
optimize your hormones,
not just testosterone and estrogen,
but also prolactin and
other hormone pathways
that impact your mood, mental
health and physical health.
Dr. Gillett is also an avid
educator about hormones
in other aspects of health.
He does this on zero cost
to consumer platforms,
such as Instagram and other social media.
On Instagram, he is kylegillettmd,
that's K-Y-L-E-G-I-L-L-E-T-T,
no E at the end, MD.
So kylegilletmd on Instagram.
And he is Gillett Health
on all other platforms,
including LinkedIn, Twitter,
YouTube, TikTok, and Facebook.
If you go to his Instagram
or his other social media,
you will learn a lot about hormone health,
about the latest science impacting obesity
and metabolic health.
He is a wealth of knowledge.
And again, he's providing
all that information
at zero cost to you, the consumer.
What you are soon to hear
is a conversation between me
and Dr. Gillett about all things hormones
and hormone health and
hormone optimization.
We dive deep into mechanisms,
but we are clear to
establish what each word
or set of concepts mean.
So if you have no background
in biology or even if you do,
I'm sure that you'll
come away with a wealth
of valuable knowledge.
We also talk about specific
protocols related again
to lifestyle factors,
nutrition, supplementation,
and where appropriate,
hormone replacement therapy.
I know there's a lot of
interest about these topics.
Dr. Gillett is very thorough
about addressing both male
and female issues and
addressing hormone health
for people at all stages of life.
I'm sure that you'll come
away from this episode
with the same impression that I did,
which is that Dr. Gillett
is an extraordinarily clear communicator
and that he has tremendous
compassion for his patients,
and that he has a deep love
of understanding biology
and medicine in ways that can benefit you.
I'm pleased to announce that
I'm hosting two live events
in May, 2022.
The first live event will take place
in Seattle, Washington on May 17th.
The second live event will take place
in Portland, Oregon on May 18th.
Both are part of a
lecture series entitled,
"The Brain Body Contract"
during which I will talk about science
and science-based tools.
Many of which overlap
with the topics covered
on the Huberman Lab Podcast,
but most of which will not and
will be completely new topics
and tools never discussed publicly before.
Both live events will also include
a question and answer
period during which you
the audience can ask me questions
directly about any aspect
of science or science-based tools
and I will attempt to answer them.
Tickets for the two events, again,
Seattle on May 17th and
Portland on May 18th,
are both available at
hubermanlab.com/tour.
Before we begin with today's episode,
I want to emphasize that
this podcast is separate
from my teaching and
research roles at Stanford.
It is however part of my desire and effort
to bring zero cost to consumer
information about science
and science-related tools
to the general public.
In keeping with that theme,
I'd like to thank the
sponsors of today's podcast.
Our first sponsor is Thesis.
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Today's episode is also
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I've long been a believer
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There are a lot of blood
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And now for my discussion
about hormone health
and optimization with Dr. Kyle Gillett.
Dr. Gillett, welcome.
- Thank you for having me.
- Well, I'm super excited to talk to you,
because I found out about you
on a podcast and
it immediately became clear
that you are an encyclopedia
of knowledge about hormone health for men
and for women across the lifespan.
So I have many, many questions,
but before we dive into those questions,
I'd love to just get a
little bit of your background
in terms of your medical training
and what your particular orientation is
toward treating your patients.
And how do you think
about this whole landscape
that we call hormone health?
What is a hormone?
How do you envision people
managing their hormones?
If you could just kind of fill in
a few of those blanks for us,
I think a lot of people
would appreciate it.
- Absolutely, so I'm dual board-certified
in family medicine and obesity medicine.
I've kind of tailored my
training in order to provide
what I call a balanced
approach to total health,
which includes body, mind, and soul.
I recently saw a podcast
with Joe Rogan and Mr. Beast.
And Joe asks Mr. Beast,
"How do you become such
an amazing YouTuber
and have all these great clickbait videos,
and how did you become good at it?"
And it turns out he just became obsessed
when he was a teenager.
And that's essentially
how I've tailored my education as well.
I've become obsessed with
optimal human performance,
their body, their mind,
and even their spirit.
So I attended med school at
the University of Kansas,
which is one of the few med schools
that still emphasizes full-spectrum care.
They emphasize exercise is medicine.
They emphasize food is medicine,
of which I was active in both
of those interest groups.
In residency, I was active in a lot
of mindfulness curriculum.
And then also things like Walk with a Doc
where you emphasize preventative medicine.
That's something that we've
kind of got away from.
And that niche led me to hormone health.
It didn't really start as hormone health,
but it's a very important
component of health in general
that many people don't emphasize.
- Great, well, this idea
of preventative medicine,
I think, is starting to really take hold
in the general population,
especially given the events
of the last few years,
people realize that they are
showing up to health challenges
at a bunch of different levels.
And with some people feeling very robust,
other people feeling back on their heels.
When someone comes to you as a patient,
what are some of the
first things that you want
to know about them?
I mean, obviously you want
to know their blood pressure.
You want to know something
about their mental health
and family history.
But in terms of hormone health,
what are the sorts of probe
questions that you ask
and what are you looking for?
And I ask this because I'd
like people to be able to ask
some of these very same
questions for themselves.
- Yeah, so when you do a physical exam
and a history, you have
a lot of different parts.
You have your history of present illness
if they have a complaint,
maybe the patient
doesn't have a complaint.
In that case, things
like their social history
and their family history
are extremely important,
because that gives you
an insight into their genetics
and an insight into their hormone health.
So patients will tell
me, oh, I'm doin' okay,
but it helps to ask them,
well, how are you now?
Let's say the patient is 50.
How are you now versus when you were 20,
and what has changed?
So I've gotten the question the lot,
how do you get your doctor
to order a better lab workup
or to even include your basic hormones?
And there's no magic answer to that,
but what really helps is you tell them,
my energy is not as good as it used to be.
My focus is not as good as it used to be.
My athletic performance is
not as good as it used to be.
So you don't have to have a pathology
in order for a lab to be indicated.
You just have that pertinent symptom.
- I think that's going
to be really helpful,
because for many people,
the idea of getting a blood test to look
at their hormones just seems like such
an enormous hurdle to get over,
and many doctors won't prescribe them.
And would you say that it's,
using the approach you just described,
that it's equally
effective for men and women
or do you find that, for
one reason or another,
that men and women have
different challenges
and advantages in trying
to access their deeper hormone data?
- Yeah. It's slightly different.
With women, there's a
lot more objective data.
So if they're having
menstrual irregularities or
if they're not havin' a period,
if they're having too heavy of periods,
then those are things that they talk about
very frequently with their doctor.
Men are more hesitant.
So men really want to know
what their testosterone is,
but at the same time,
they really don't want
to tell their doctor
how their libido is or
how their energy is,
because it's almost like
they feel less masculine
or they feel less like
a guy when they say that
even if they're just talking
to their doctor about it.
- Yeah, I think that that
raises a really important point,
which is that the whole
discussion around hormone health
is a bit of a barbed wire topic,
because in many ways when
we hear the word hormone,
we think testosterone and estrogen,
we think notions of
masculinity and femininity.
And of course testosterone
and estrogen are present
in all sexes, right?
All chromosomal backgrounds.
And just varying degrees in ratios.
But it also raises all these
issues about sexual health that
it's kind of interesting,
'cause I'm surrounded by medical doctors
in my lab at Stanford.
And the more physicians
that I surround myself with,
the more open is the
discussion around sexual health
and reproductive health.
But in the general population,
I think some of these topics
are a little bit taboo
or against kind of barbed wire.
And so I think that people are seeking
a lot of this information on YouTube
and through communities that may
or may not be very educated
about the actual biology.
So along those lines,
we could probably assume
that hormones are changing
across the lifespan, right?
Certainly from childhood
and puberty and onward.
If you would,
I'd love to just kind
of take a snapshot of
what you think everybody
should be thinking about
or doing to optimize their hormone health,
male or female, in,
let's say in their 20s.
And then maybe we could migrate
that to their 30s and 40s.
But before that,
could you just tell us what
everyone should be doing
for their hormone health
from puberty onward?
- Yeah, the law of
diminishing returns applies.
So doing a little amount
of what I call lifestyle interventions
over a long period of time is
going to be far more helpful
or efficacious than doing a
lot and then doing nothing
or doing a lot and then doing nothing.
So I talk about the big six pillars.
The two strongest ones are
likely diet and exercise.
For hormone health,
specifically resistance training
is particularly helpful.
For diet, caloric restriction
can be particularly helpful,
especially with the epidemic
of metabolic syndrome
that is continuing to
on go in this country
and in developed countries in general.
So those are the two most powerful.
So number one and number
two are diet and exercise.
For the last four, I have a
little bit of alliteration.
So there's stress and stress optimization.
That has to do with cortisol,
that has to do with your mental health,
that has to do with societal health,
and collective health
of your family as well.
When you're a member of a family
or even a very close friend
trying to achieve optimal health
together is very important.
It's the same thing
with nicotine cessation.
It's the same thing with
hormone optimization.
If you do it as a household
unit, it's far more helpful.
So after stress, you
have sleep optimization.
Sleep is extremely important,
especially for mitochondrial
health as well.
And then you have sunlight,
which encompasses
anything that's outdoors.
So you move more, you have cold exposure,
you have heat exposure, that's sunlight.
And then last one is spirit.
So that's kind of the
body, mind, and soul.
If you have all the other five in,
they're dialed in completely,
but you don't have your spiritual health,
whatever you believe,
then that's going to
profoundly impact your body
and your mind as well.
- Yeah, and we're definitely
going to touch into this notion
of spiritual health,
because I think for some people
that might draw connotations
of certain things that may
or may not be accurate,
but I know a number of
academic laboratories
that are focused on this and a number of,
not just functional medicine clinics,
but research clinics and
hospitals throughout the country
that are achieving some
really interesting data,
not just in people that are quite sick,
but in healthy people who are trying
to further optimize health.
So we will definitely touch back to that.
If you would be so kind
as to maybe give us
a little bit more detail about
some of these other areas.
So when people hear diet,
I immediately think, okay,
now we get into
the combat around vegan,
plant-based, carnivore, et cetera.
But I think that my general view of this
is that most people
should probably be eating
as few highly processed foods,
highly palatable foods as possible,
which doesn't mean eating foods
that don't taste good, of course.
But what other sorts of
things do do you recommend
in the realm of diet?
And then I also want to know
about caloric restriction,
because my understanding
is that a caloric surplus
can actually support certain
hormones like testosterone.
So how does one combine
caloric restriction
and still optimize hormones?
But what would you say
is a really terrific way
to think about an approached diet?
- Yeah. Diet should be an
individualized approach.
So if you have a car,
each car is made different and requires
a different sort of fuel,
whether it's a race car,
whether it's a diesel truck,
they have different fuels
for different performance outcomes.
So if you're trying to tow something
or you're trying to go fast.
So it's the same way with athletes.
It's pretty well studied.
The more intra-workout carbs
ultra long distance athletes take,
in general, they do better.
I think they've studied this
in cyclists quite often.
It also depends on your genetics.
So you can have a genetic polymorphism
and you metabolize carbs and sugar better,
even when they're unopposed by fiber.
- How does one determine whether
or not they have such a polymorphism?
I mean, I'm an omnivore,
so I do eat some high quality meats,
not in huge quantities,
but I also eat vegetables
and starches, I feel fine.
I've never done an elimination diet.
I think I did a very low carb diet once
and all it gave me was a lot
of psoriasis and poor sleep,
so I backed off.
I probably didn't do it correctly,
but I know a lot of
people that do quite well
on a very low carb or zero carb diet.
- Yeah, particularly those
who are at risk of cancer,
because you have less glucose
that can be easily uptaken into cells.
And then also people
with autoimmune diseases.
- They tend to do well on auto-
- On lower carb diets, yeah.
But yeah, as far as the how do you know,
basically you can use your biofeedback,
how you're feeling, to guess
what you tolerate well,
or you can just get genetic testing,
which can be fairly
expensive, but most of all,
it requires a physician
or someone who knows how
to interpret the test accurately.
- And if someone had the means or
would you say that getting
regular blood testing
is a good idea?
And if so, what is regular blood testing?
Is it every three months?
Is it every six months?
Of course the backdrop
of life is changing too,
stress levels, et cetera.
- Yeah, every three to six
months for preventative purposes,
at times you need blood tests
at faster frequencies than that.
And then you should also get a blood test
when you're fasting and
when you're not fasting.
So if you're looking
for damage to the beach,
you don't just look at low tide,
you look at high tide and
you see what's happening
at high tide as well.
- I think that's a great way to put it.
And in terms of general
recommendations around exercise,
I mean, I'm of the mind,
based on the data that I've seen,
that almost everybody should,
or everybody should be getting
150 to 180 minutes minimum
of Zone 2 cardio per week
that kind of could continue
while having a conversation,
but if one were to exert any more effort,
it would have a hard time
getting the words out.
At least that, right?
For cardiovascular health
and general brain health
and musculoskeletal health
plus resistance exercise.
Is that more or less the
contour of what you recommend?
- Yeah, that's more or less the contour.
The more you're doing your
Zone 2 cardiovascular exercise,
the slightly less
important a long duration
of caloric restriction is.
- Interesting, and that brings
us to caloric restriction.
So it's very clear that
caloric restriction
can allow one to lose weight, right?
This is the classic CICO, C-I-C-O,
calories in calories out.
We are not disputing
calories in calories out.
But somehow that always
has to be stated 50 times
in any forum because of whatever follows,
people I think will anchor to,
and assume that we don't mean that,
but I know you and I both agree
on calories in calories out
as a fundamental law of thermodynamics.
But it's clear to me that
based on what I've read
that when one is in a
slight caloric surplus
that hormones like
testosterone can be optimized,
but is that true for
somebody who's showing up
with excessive body fat?
How does this all work?
Because body fat is manufacturing enzymes
that convert testosterone to estrogen.
So in other words,
how does someone know if they
should use caloric restriction
or avoid caloric restriction?
- Yeah, here's how to parse that out.
So before I delve into the
details a bit more, I should say,
as a board-certified
obesity medicine physician,
obviously the laws of
thermodynamics apply.
And then in addition to that,
there is nothing special
about intermittent fasting
or caloric restriction
or exercise when it pertains
to losing body weight in general.
When you do lose weight,
about 33% of that is lean body mass.
And about 10% of fat cells,
adipose cells are actually
lean body mass as well,
because it has proteins and water
and things like that in it too so
the reason for exercise
and the reason for caloric
restriction in general,
including intermittent
fasting, is health reasons.
That's how you increase your health span.
It's not necessarily
going to make the weight
on a scale change, but that
doesn't matter as much.
It's been fairly well studied
in both mice and humans.
It's much easier to study in mice.
So that's a precursor to
our six types of people,
the ones that care about mice studies
and the ones that care
about human studies.
But if you correctly restrict mice by 40%,
than they can
have improved testosterone parameters,
but only if they're obese to start.
And it appears to be that
same way in humans as well.
So the easy way to think about it is
if you're obese or you
have metabolic syndrome,
caloric restriction will
improve your testosterone.
There has been a study and they
talk about all these studies
in a systematic review from
the Mayo Clinic Proceedings
in March of last year.
And they note that there is a study
in young, healthy men and
they calorically restrict them
and their testosterone does decrease.
So if you're young and healthy
and you don't have metabolic syndrome,
then caloric restriction
will likely decrease your testosterone.
- That clarifies a lot for me.
And I believe it will clarify a lot
for other people as well.
And I'm delighted that you
pointed out this distinction
about intermittent fasting
not being the only way
to achieve caloric restriction.
There are a number of young, healthy,
or older, healthy people I know
who like using intermittent fasting,
even if they're not trying to lose weight,
for a couple of reasons.
Some believe that it
might extend lifespan.
I think that's still a
bit of an open question.
It's a bit of a hard experiment to do,
because the control group is,
no one wants in the
control group as I say.
- It does in mice.
- Right. Exactly.
- Captive audience.
- Exactly, and the other
feature of it that's
a little bit tricky is that many people
like intermittent fasting
because of the mental effects,
the clarity of mind that
they feel during fasting,
the increased pleasure in
eating when they finally do eat
and here I'm referring
to intermittent fasting
of the sort where eating
windows are anywhere
from 8 to 12 hours a day.
Not extended fasts of 24 hours or more.
So the question therefore is,
for the healthy lean enough person, right?
Non-obese person, is
intermittent fasting a bad idea
in terms of hormone health?
Is oscillating between this period
of kind of feast and famine
within a 24 hours a problem
if one is getting sufficient
calories to maintain weight?
- Yeah, so if they're in
a caloric maintenance,
then it's not going to be,
it's not going to be deleterious.
It's not going to be bad
for their hormone health.
There's a couple different
hormones that we can talk about.
We can talk out testosterone.
We can talk about DHEA, which
usually go hand in hand.
And then we can also talk
about growth hormone,
which is not a steroid hormone,
but it's a peptide hormone.
So it's a chain of proteins,
amino acids that are put
together instead of a sterile,
think of sterile hormones
as coming from cholesterol.
So intermittent fasting,
you do get a little spike in
growth hormone after you eat,
but you also get a huge
spike in growth hormone,
a more significant, less
negligible spike overnight.
And that is improved if you
are intermittent fasting.
So it's probably going to
help your growth hormone
and subsequently IGF-1 levels,
which will help more
in the older age groups
than younger age groups.
- And I like to eat dinner.
So for me, that means sometime
around six or seven o'clock,
sometimes eight o'clock.
I confess last night,
'cause I was working late,
I ate pretty big,
it was basically my only meal
of the day, at 10 o'clock.
That's a rare thing for me.
Can I still achieve a high
degree of growth hormone output
if, let's say I avoid food
in the two to three hours
before going to sleep?
Or does one have to be very
deep into a fast in order
to achieve the increase in growth hormone?
- There's still pretty
good growth hormone output
even if you eat two or three
hours before you sleep.
It's just the law of diminishing
returns, the longer you go,
you get slightly more and slightly more.
- Right, and I know a
number of people think
of growth hormone in the context
of the exogenous growth
hormone and the fact
that that can, in some cases,
be associated with cancers.
I've been asked many times before,
can the increase in growth
hormone from things like saunas
or intermittent fasting cause
levels of growth hormone
that are so high that they cause cancers.
My impulse is to say, no,
it seems like it's not like to happen,
but I should probably verify
that statement with you.
- Yeah, so quite unlikely.
I think about growth hormone,
and especially IGF-1.
And there's actually an IGF-1 and IGF-2.
But I think about it in
terms of endocrine IGF-1,
mostly IGF-1 that's
synthesized in the liver
and released in the liver
versus IGF-1 that's released classically.
An example of this would be
your IGF-1 levels increase
after resistance training or exercise.
And that's more of like
paracrine or autocrine,
and they have more local action.
So that IGF-1,
it's pretty well studied that
if you just give people IGF-1,
it's not going to, at physiologic levels,
it's not going to improve
their body composition.
However, that IGF-1 that's
autocrine and paracrine
just working in those
local tissues and muscles
is likely part of the reason why you get
a improved body composition
response after exercise.
- I see, and just to clarify
for me and for others,
what can we say are the
major functions of IGF-1
and IGF-2 that are distinct
from just growth hormone?
Are they just kind of the
active hormone growth hormone?
The kind of the pickaxe end
of the assembly line?
- Yeah.
So they have a much
longer duration of action.
I believe the half-life of IGF-1
is several days almost a week,
whereas growth hormone has
an extremely fast half-life
of only hours.
So growth hormone acts
significantly on the liver
to produce IGF-1.
So it's around
in the serum in the blood long enough
to where it's producing an
effect pretty much all the time.
- Very interesting.
- Yep.
- Well, and then your
other pillars, stress,
we've talked a lot about
stress on this podcast before
and tools for managing stress.
Sleep obviously is a big one.
I think, if nothing else,
I will either put people
to sleep with my podcast.
Certainly not one,
but my solo episodes or
hopefully convince people
that sleep is the foundation of mental
and physical health and performance.
Are there any aspects
of hormone optimization
that can improve sleep?
I know sleep can improve
hormone optimization,
but are there any aspects
of hormonal optimization
that can improve sleep?
And for people that are suffering
from this common syndrome
of going to sleep and then
waking up at 03:00 or 04:00
in the morning,
we know that can be
associated with depression,
but are there any hormonal
indications that might lead
to that kind of situation?
- Yeah, there's three big ones.
The first one is not super common,
but it's a very direct correlation.
If you have a growth hormone
deficiency, a true deficiency,
whether you're an adult or a child,
then your sleep is likely
going to be affected.
And let's say you're a child
with growth hormone deficiency,
once that is replaced with therapy,
your sleep is going to
get significantly better.
The second one that's
a very common scenario
is if you're having what's
called vasomotor symptoms
of menopause or vasomotor
symptoms of andropause
which are also applicable.
And that's where your
progestogenic activity,
so your main progestogens are progesterone
and then and pregnenolone
and then 5-alpha,
3-alpha-progesterone, which is-
- Where are those
manufactured in the body?
- So they're manufactured in a few places.
In men, they're manufactured
some in the testes
in the Leydig cells.
In women, they're manufactured
in the ovaries until menopause.
And then they're also
manufactured in the adrenal gland.
So if you're pre-adrenopausal
where your adrenal glands are
still working fairly well,
usually still have a decent
amount of progesterone around,
and this can be measured too.
So after menopause,
women make progesterone
from their ovaries,
or sorry, from their adrenal glands.
If that progesterone crosses
the blood-brain barrier,
especially if it's 5-alpha
and 3-alpha reduced,
so it's modified a little bit,
then it is both a GABA agonist,
which helps sleep just like GABA does,
gamma-amino butyric acid,
the main inhibitory neurotransmitter
of which lots of things work on,
alcohol works on GABA as well.
Gabapentin also works on GABA.
Migraine medicines, many
of them work on GABA.
Benzodiazepines, and also non-benzos.
So an example of a benzo would be Xanax.
An example of a non benzo would be Ambien.
So those all work on GABA.
So GABA is also helped by
the progestogenic activity as well.
That's why a lot of women in
menopause feel like their sleep
is much worse is because
they have lower activity
of those progestogens.
- And for men in so-called andropause,
low testosterone, is that
also one of the causes
of poor sleep.
- Low testosterone can lead to poor sleep,
nut my third scenario is actually,
if a man begins TRT,
then they develop poor sleep
because of sleep apnea.
It drastically raises
the risk that somebody
is going to have sleep apnea.
And then a lot of people,
especially when they first started
in the first month or two,
it puts them into this
hypersympathetic state,
because they have overactive
androgen receptors,
especially after a long
time of being hypogonadal.
Then they have a physiologic dose of TRT
and that causes the sleep issue itself.
- Interesting, I have a
lot of questions about TRT,
testosterone replacement therapy.
I should just mention that when you say
it increases sympathetic activity,
you don't mean that taking testosterone
increases sympathy for others.
It may in fact do the opposite.
Although it's very clear
from my discussions
with my colleagues
in the endocrinology side and also with
the great Dr. Robert Sapolsky
that increasing testosterone
merely exacerbates existing
features of people.
So the jerks become bigger jerks,
kind people become even
more kind in general,
but I want to get into TRT in depth,
but it's very interesting to me
to hear that testosterone
replacement therapy increases
the risk of sleep apnea.
And I want to make sure that I ask that
is that also the case in
people that are using TRT
who are not hypogonadal?
Because in the classic situation,
if somebody isn't making
enough testosterone,
they're below 300 nanograms
per deciliter on the chart,
they go in and take TRT.
But many people nowadays, let's be honest,
are taking doses of testosterone
even though they are in
the sort of standard range,
because the range is so large because
of other symptomology, is that right?
- Yeah, I do love the
analogy that Dr. Sapolsky had
about monks taking testosterone
and making them more and more generous.
So that does appear to be what
testosterone usually does,
is it exacerbates, if you will,
what you're previously like.
So it's not going to
change you as a person.
But if you're eugonadal
before you start testosterone-
- Meaning?
- Meaning you have normal testosterone,
and then you start TRT or
self-administered TRT,
steroids, however you want to look at it,
then your risk of sleep
apnea still goes up
in a dose-dependent fashion.
So the higher the dose, the more risky.
With the sympathetic and the
parasympathetic nervous system,
the sympathetic is the fight
or flight nervous system,
the parasympathetic is
the rest and digest.
So if you have too much fight or flight,
and stress can cause that too,
then you're not going to
rest as well at night.
- I want to touch on
testosterone in women because
there is testosterone in women.
I'd like to know where that
testosterone comes from,
which tissues, I'd like to know whether
or not testosterone replacement
therapy make sense in women.
I'm hearing more and more
about women using testosterone.
And I'd like to know
whether or not knowing
a woman's testos,
for her to know her
testosterone is of equal,
less than or more value
than knowing, for instance,
progesterone and estrogen levels?
Because I think there are a
lot of misconceptions about
the roles of testosterone in women.
- For health optimization,
testosterone is just as important to know.
For pathology prevention, for example,
breast cancer, osteoporosis,
estrogen, and progesterone
are more important to know.
So when you're thinking about women,
women think that they
have such a tiny amount
of testosterone, because you test it,
most people test a free testosterone,
so a testosterone that's unbound,
which is by far
the smallest proportion of testosterone.
Any androgen is bound by lots
of different steroid-binding proteins.
But the ones that are most
pertinent are called SHBG,
or sex hormone-binding globulin.
And that binds the androgenic steroid,
for example, DHT or dihydrotestosterone.
It's associated with prostate enlargement,
it's associated with
male pattern baldness.
It binds that the most strongly,
and then it binds testosterone
next most strongly,
and then it binds things
like androstenedione
or DHEA, dehydroepiandrosterone.
And then it binds the estrogens,
the weakest, like estradiol.
So if you look at the total
amount of testosterone,
women actually have, almost
all women, not all women,
but almost all of them have
significantly more testosterone
than estradiol, but it's because it's
in different measurements.
So estradiol, a lot of
time is picograms per mil
as opposed to nanograms per deciliter.
So women have more
testosterone than estrogen
and significantly more DHEA than either.
- Interesting. Do women
make dihydrotestosterone?
- Yeah.
- And where does this
testosterone come from?
Because they don't have testes.
- Yeah, so most testosterone in women
that are premenopausal can come
from theca cells, T-H-E-C-A.
So theca cells are cells in the ovaries
that can produce testosterone.
And a lot of people have actually
heard about hyperthecosis,
not the term itself.
But a lot of Olympians that are,
their chromosomes are XY, they're females,
and they're not taking any-
- Wait, they're XY,
but they're females?
- Or sorry, they're XX.
- Oh, okay.
- Yeah. Thank you.
So they're XX, they're not XY,
and they have never transitioned or been
on any sort of hormone
replacement or testosterone,
but they naturally produce a
huge amount of testosterone,
as much as many men.
And some of these women,
I believe they were from Botswana,
were banned from competing in the Olympics
in certain distances.
I believe they were banned from
the 400 meter and 800 meter,
because their natural testosterone
was deemed to be too high.
- So they mistakenly thought
that they were using steroids?
- They actually knew they
were not using steroids.
They knew it was their theca cells
were just genetically gifted, I suppose.
And they still made them change distances.
- [Andrew] Wow.
- So one or two of these
athletes changed to,
I believe it was the 3K or the 5K,
and they still did quite well,
but it was not their best event.
- Interesting, yeah, that's turning out
to be a very interesting
and controversial area
of this notion of hormone
therapies and natural variation
in hormones on different
chromosomal backgrounds.
Fascinating, we should probably do
a whole episode about that,
'cause it's very much of the times.
So men and women both make DHT.
I'd like to ask about DHT in men.
So often we hear about testosterone in men
and free testosterone being
the unbound form of course.
But dihydrotestosterone, where
does it come from in men?
What is the cascade of events
that takes testosterone
to dihydrotestosterone and what are some
of the quote/unquote positive
and negative effects of,
here I'm only referring to
endogenous dihydrotestosterone.
And in fact,
I'll make it very clear whether or not
I'm talking about taking something
or one's own natural production.
Here we're just,
I think up until now we've
just been talking about
natural production.
So tell us about DHT in men,
such a powerful hormone
during development obviously.
But what is it doing?
- DHT is a very androgenic hormone.
So whether you're talking about DHEA,
which is a weak androgen,
or testosterone, which is a
relatively strong androgen,
or DHT, which is a very strong androgen,
they bind to the androgen
receptor in both men
and in women.
So the effect of all
three of those is mediated
by the androgen receptor.
There's a couple different
beta-estradiol receptors
and alpha-estradiol receptors,
but there's only one androgen receptor.
Intriguingly, it is on the X chromosome,
so men get their androgen
receptor gene from their mother.
Women get one androgen receptor
gene from their father,
one from their mother.
Often the one that is more
sensitive to androgens
and people with PCOS, that's
the one that's active.
The other one is methylated and inactive.
- Can I just pause you one second?
Sorry to interrupt,
but I have to ask this
question before I forget.
And I know a number of people
are probably wondering,
I've heard that whether
or not one develops male pattern baldness,
whether or not a male develops
male pattern baldness,
just to be very precise,
you could get some information
about that by looking
at your mother's father,
and that would, in keeping
with what you just described,
that the X chromosome,
which of course is handed
off through the mother,
is carrying the genes that encode
for the number and distribution
of these androgen receptors
that DHT will bind to,
'cause of course,
I think as you'll probably tell us,
that DHD is a responsible
for male pattern bald and
beard growth, is that right?
Should I look at my
grandfather on my mother's side
to determine what I'm
likely to look like in terms
of my DHT-ness, is that a word?
- Yeah, it's the best guess
that you could make
purely from phenotypes.
Now you can measure your genotype and
get a better idea of that.
Assuming that it's true
male pattern baldness,
it's related to the gene transcription
of the androgen receptor.
So I like to think of
it as how much of this
androgen receptor gene is
activated by any androgen?
So if you have an
extremely sensitive gene,
which usually means you
have very few CAG repeats,
which is basically just
a certain, CAG encodes
for a certain amino acid,
and if you have very few of the repeats,
then your androgen
receptor gene works better.
Think of it as a corollary
to Huntington's disease
where if you have very few of,
called trinucleotide repeats,
then it's not as severe as a disease,
but after you get more
and more CAG repeats,
which by the way are,
in the population you're getting
more and more CAG repeats,
so it's a natural selection of process
that has been ongoing for a
variety of number of reasons.
But anyway if you have more repeats,
then that gene activates in the cytoplasm
and moves to the nucleus
and causes gene transcription more often
and hair loss more often.
- So does that mean that we're
seeing more hair loss now due
to elevated levels of DHT
than we were 50 years ago?
- Probably not.
The hair loss 50 years ago,
well, not 50 years ago,
but 500 years ago,
was probably more significant,
because on average, 500 years ago,
people were more sensitive to androgens.
So there's a syndrome called
androgen insensitivity syndrome,
AIS and that syndrome
was related to when men,
who have the copy from their
mother who is a carrier,
their AR gene, or androgen receptor gene,
is completely insensitive.
So think of it,
it's not related to the CAG repeats,
but think of that receptor
as just not working at all.
So there's a continuum,
so everybody's receptor
works a little bit better
or a little bit worse.
And the better your receptor works,
the more likely you are to
have male pattern baldness.
- To zoom out from this, but
still keeping an eye on DHT,
what do you like to see
all women in all men do
to optimize DHT?
And here I'm talking
about regardless of age.
So we're still in this
from puberty onward phase.
We haven't yet micro-dissected
out decade by decade,
which we will do,
but what do you like to see
people do to keep DHT in check?
But before you tell us that,
could you tell us what
positive things DHT does
when it's in the proper range?
- Yeah, so DHT helps a lot for,
it's the same reason
why testosterone helps,
it activates the antigen receptor gene.
It helps effort feel good.
So it can be motivating.
So that's how it's active in the CNS.
It also is active in
cardiovascular tissue.
So if you look at someone
that has heart failure
or if someone has cardiac hypertrophy,
the level of DHT can matter
because it's also binding
to the androgen receptor in the myocardium
or in the heart itself.
So you think of the
classic bodybuilder heart.
It's an easy example to make.
They have very thickened muscle.
Their muscle is very strong,
because they're pumping blood
often with high blood pressure
and that DHT and the testosterone
and any DHT derivatives like
Masteron or oxandrolone,
preamble and also bind to the heart,
and they cause even more hypertrophy
or enlargement of that muscle tissue.
So then let's say the person
stops and they're recovering,
and they're trying to
have cardiac remodeling,
which is where you take
a very thick heart,
and cardiac remodeling's important
in a lot of different cardiac pathologies,
but if you give them
finasteride or dutasteride,
which inhibit the enzyme that
can converts testosterone
to DHT, so making less activity
at the androgen receptor gene,
they have cardiac remodeling,
and their heart health improves.
- I see, so for the non-body builder,
the typical woman or
man, younger or older,
what sorts of things support
DHT, and thereby heart health?
Presumably DHT she is involved
in some of the other things
that testosterone is famous
for in both men and women.
Things like libido, as you mentioned,
making effort feel good.
So motivation, drive and vitality is,
I guess, could be the general phrase.
What sorts of things support DHT?
What sorts of things
create problems for DHT?
- There's lots of dietary
changes and supplementation
that you're probably doing right now
that's affecting your DHT.
- You mean me personally?
- Well, everybody.
All of the listeners.
Because let's say you have a diet high
in plant polyphenols,
many of those inhibit the enzyme
that converts testosterone to DHT.
- Could you give us an example
of one of those, either
in supplementation form,
or in food form?
- Curcumins, certain curcuminoids,
depending on the structure,
will inhibit the enzyme
called 5-alpha-reductase
that converts testosterone to DHT.
- Turmeric?
- Yeah. Turmeric.
Black pepper extract.
So it's used often to
increase bioavailability.
It's also called BioPerine.
It's also a 5-alpha-reductase inhibitor.
And on top of that, people
have different genetics too.
So some people, they're
5-alpha-reductase enzymes,
there's three of them.
They're on chromosome two,
three, and four, I believe,
but some of them are
active in the prostate,
some of them are active in the brain.
And so it depends on which tissue,
they're tissue-specific
enzymes that depend on
how much DHT you convert.
- Do you recommend that
people avoid curcumin
and turmeric for that reason?
And is there any specific recommendations
for men versus women.
- If a man or a woman, by the
way, in women, a lot of times,
if you just ask your
doctor for a DHT check,
it's the same units as in men,
so it's essentially undetectable.
So you have to,
especially if they're
on oral contraceptives,
which is a front topic,
their DHT is very likely undetectable,
especially if it's free DHT.
You can measure both a DHT and a free DHT.
But if someone's DHT is already low,
or if they have somewhat
insensitive androgen receptor
via genetics or via lifestyle,
then I recommend they avoid
bioavailable curcuminoids
like bioavailable turmeric,
black pepper extract,
and they might be a good
candidate for creatine.
Creatine, like creatine monohydrate,
can significantly increase the conversion
of testosterone to DHT.
- Interesting, there's also a lot
of really interesting
data coming out now about
the role of creatine as a brain fuel,
and maybe even as a
cognitive enhancer over time.
The data is still ongoing,
but some of the studies in
humans are pretty impressive,
at least to me.
I'm glad you mentioned
this thing about curcumin
and black pepper.
I wish we had had this
conversation six years ago,
because I had the experience
of jumping on the bandwagon
of the excitement around turmeric,
and I took a turmeric supplement.
It was a couple capsules
of what I thought to be,
and I think was high quality turmeric,
and I've never felt as poor as I did
in the subsequent few days,
flat line of, let's just say everything
that one would want to have
in life, energy, vitality,
just it was a cliff.
And a friend somehow knew that curcumin
could inhibit 5-alpha reductase.
It converts to testosterone
to DHT, as you pointed out.
I stopped taking it,
it was the only new addition
to my diet and supplementation,
and things bounced back
within about three, four days.
But it was remarkable.
I mean, I felt like garbage.
And it was actually kind of frightening
to experience the sharpness of that cliff.
But I know that some people like turmeric
for its antiinflammatory
properties, et cetera.
Sounds like people either
need to experiment,
and if they do,
obviously to approach that with caution.
Anytime you add or remove something,
you need to talk to your doctor.
You're a doctor, and I'm guessing that
if one were to experiment,
would you say that most of these effects
of things like curcumin are
reversible as they were in me?
Or is there any potential
of permanent damage
if people have been taking
them for a long time?
- The effects are nearly always reversible
when you're talking about
5-alpha reductase inhibition,
so what turmeric does, but stronger.
The most common story
that we hear is regarding
a supplement known as saw palmetto,
which a lot of older men take
for their prostate health or finasteride,
which you can take for your prostate,
or your heart, or your
hair, or dutasteride.
So if you're having side effects on these,
then it's probably because of
a couple different reasons.
One can be your ratio of
androgens to estrogens is off,
and that needs addressed.
Another one can be it's
inhibiting the conversion
of your progesterone to that
other type of progesterone,
the 5-alpha, 3-alpha, that
we talked about earlier
that's helping with your
sleep and your brain,
and your calmness.
And that's definitely an effect.
Another one is depending on
the type of supplement or med,
they inhibit different isoenzymes
of that 5-alpha reductase.
So if they're just inhibiting one and two,
then that's going to be
a different effect than
if they're inhibiting two and three.
So finasteride does two and three,
saw palmetto does one and two,
and then dutasteride does all three.
The third one is active in the brain
and dutasteride inhibits that third one
a little bit weaker in vivo,
but strongly in vitro.
So it's really hard to parse out.
You can use biofeedback
and experimentation.
I do think with supplements
it's safe to experiment.
The time that it takes to set in
is usually about three months.
So the risk of, and this is anecdotally,
there's been lots of
research published about
if post-finasteride
syndrome is real or fake.
And it is real,
but it's one of those things
that's a combination of
organic and inorganic disease.
Almost kind of like fibromyalgia
where it's definitely real,
And there's lots of things that
you can do to help with it,
but it's very unlikely to occur
if you stop taking your
supplement or medication
after you have side effects.
- Interesting, well, I
certainly feel better
when I'm taking five grams of
creatine monohydrate per day.
I know most people take
it for muscle growth
and tissue repair and things of that sort,
mainly I think brings water
into the muscle tissue,
et cetera, but I take it
for the brain effects,
and also because I like
to think that it gives me
a little bit of a DHT bump
that I can actually see in
my blood charts when I've done them.
I know many people want
to avoid the hair loss
that can sometimes be associated
with DHT levels going too high.
And so I've been asked many times,
does creatine monohydrate cause hair loss?
It would make sense that
if creatine increases DHT
and DHT binding to the androgen receptor
on the scalp can induce hair loss,
that that would be the case.
Is that that true or
are people just overly
concerned about something
that's trivial or non-existent?
- Each male and fem, so yes,
it can potentially add it.
I don't like to say it causes it,
but it can be a little
bit more fuel to the fire.
So just like everybody has
a different sensitivity
of their androgen receptor,
they have a different
amount of gene transcription
that is going to cause
death of the follicle.
That's an arbitrary threshold.
So you don't really know
until you start losing hair.
- And if somebody takes
a little bit of creatine
to increase their DHT,
maybe for the cognitive enhancing effects,
or for whatever reason,
and they notice a bit more
hair falling out in the sink,
and they stop taking it,
you said death of the follicle,
which sounds very dramatic.
Are those little stem cell niches
that reside in the follicle,
which hairs grow from,
are those then abolished,
like there's no going back,
or can one rescue at the hair?
- It takes months, if they're still there,
the hair will come back.
So the loss of the hair itself
is a normal part of the hair cycle.
So you have your antigen
phase, your catagen phase,
your telogen phase, and
then your hair loss,
and then a new follow.
- Of the stem cell niche
in the hair follicle.
- Yeah. Yeah.
Think of it like sharks have teeth.
So shark loses a tooth,
and they have a new
one that comes through.
Or losing your baby tooth,
and you have a new one,
but your hair just always
keeps coming through.
So it's natural for it to die and lose.
That's that's why when you start
5-alpha reductase inhibitors,
often you have a big shed.
So what happens during that big shed
is all of these cells that are unhealthy,
they immediately jettison that hair
and then they start making a
much healthier new follicle.
So a lot of the hairs that are
at the end of their telogen phase,
then they have what's
called telogen effluvium,
which also happens after pregnancy,
also happens in thyroid pathologies.
So you shed it, a new one in place,
and you think that you're having
a horrible hair loss
caused by your finasteride
or whatever you're doing.
And minoxidil does this too,
but you're really just having
a new, healthier follicle.
If you go a really long
time, if you go a year,
then those hairs might come
back, and they might not.
- So for simplicity's sake, if
somebody is concerned about,
or is experiencing hair
loss, male or female,
what are their options of
ways to offset that hair loss
that are not going to negatively impact
other tissues sensitive to DHT?
And what I'm basically saying here is,
I could imagine taking a DHT inhibitor,
a pill of some sort,
or an injection of some sort,
and offsetting hair loss,
maybe even stimulate more hair growth.
It's clear that I'm not doing that,
but I know people that do,
but then experience some of
the other negative effects
of blunting DHT, reduced
affect, reduced libido,
reduced drive, disruptions
in prostate function,
or even sexual function generally.
So what can people do
if they want to maintain
or grow back hair,
but they don't want all
those other effects?
What should they avoid
and what should they
perhaps consider talking
to their doctor about?
- Yeah, there's a whole host of options.
I try to separate alopecia or hair loss
into two different categories,
male pattern baldness,
or androgenic alopecia,
also known as androgenetic alopecia,
versus other types of alopecia,
usually telogen effluvium.
And if it's androgenetic alopecia
or male pattern baldness,
even if they're female,
perhaps say PCOS, something like that,
then you want some sort of
strategy to decrease the activity
of that androgen receptor.
- So women can get male pattern baldness?
- [Kyle] Absolutely.
- Okay, I'm going to have to wrap my head
around that one, but okay.
- So there's a lot of different
things that you can do
that are topical.
The most promising is called
dutasteride mesotherapy.
Essentially what it is
is it's very localized injections in areas
that are prone to male pattern baldness,
whether they're female or male.
And it acts locally only.
And you repeat these
injections from time to time,
it decreases the conversion
of testosterone to DHT
just in the scalp.
- So that can avoid prostate effects.
And what are some of the negative effects
of blocking D HT in
females, in the periphery?
Meaning not on the scalp or in the brain?
Where is DHT doing its stuff?
- Yeah, so it's both DHT,
and then also that 5-alpha,
3-alpha progesterone,
which is called THP or dihydroprogesterone
or tetrahydro, trihydroprogesterone.
So they're active in the
central nervous system,
but it's also just active, again,
binding to the androgen
receptor in a female as well,
causing them to have that
effort feel good, motivation.
A lot of women that are sensitive to DHT,
'cause women can be
sensitive to DHT as well,
feel very different when they
start an oral contraceptive,
not because it alters
their DHT to a huge amount.
It does to some degree.
Because the negative feedback inhibition
in the pituitary and less
produced in the ovaries,
but it increases SHBG really high.
So because their SHBGs
are significantly higher,
their free DHT is way lower.
- I see, how does a woman
know if she has PCOS,
polycystic ovarian syndrome?
What are the issues with
polycystic ovarian syndrome?
What can be done about PCOS?
I confess, I was naive to PCOS.
That wasn't supposed to
rhyme, but since it does,
I do confess I was completely naive to it.
And I started getting a
lot of questions about it
in various forums.
And I think that's actually the reason
why I initially approached you.
I know you have treated a lot of PCOS.
What age women should be
about PCOS, what's PCOS?
Teach us about PCOS, please.
- Yeah, so PCOS is
polycystic ovarian syndrome.
And this is one of those conditions
which is underdiagnosed.
So its prevalence is much
higher than we think it is.
There's been a lot of studies.
And some studies say a
prevalence of 10%, some say 20%.
It's not completely clinically penetrant.
So most people don't know they have PCOS
until they have infertility
or subfertility.
- And is PCOS happening at this frequency
in 20-year old women,
in 30-year old women,
in 40 and onward?
- Most women find out they
have PCOS in their 30s,
especially, it's on a
spectrum or a continuum,
like a lot of things, where
you can have a weaker version,
or a very severe version.
- What are the symptoms?
- There's criteria called
the Rotterdam criteria.
And in the Rotterdam criteria,
there's a couple different
ways that you can diagnose it.
You're looking for androgen
excess, insulin resistance,
and you could also look
for polycystic ovaries.
You don't actually have to
have polycystic ovaries or
to get an ultrasound of your
ovaries to be diagnosed.
If you have androgen excess, for example,
androgenic acne, or hormonal acne.
If you have hair growth,
like a hair growth on the
chin, it's called hirsutism.
Or if you have,
like deepening of the voice,
any symptom of too much.
And male pattern baldness,
if you're female,
that's a symptom of PCOS as well.
Then you can also have insulin resistance.
So this is obesity.
It's pre-diabetes, a high fasting insulin,
a HOMA-IR over two,
a fasting insulin of over six.
So if you have significant
insulin resistance
and also androgen dominance,
that's a sign of it.
Androgen dominance often leads
to what's called oligomenorrhea.
So if you're having more
than 35-day intervals
in between a period or if you
have less than nine per year,
then that can be a sign
that you have oligo,
which means too little,
menorrhea which means menses.
So that's a very common sign of PCOS.
If you have infertility,
so if you're under the age
of 35 and you've been trying
for more than a year, or if
you're over the age of 35,
and you've been trying
for more than six months,
then that can also be,
it's a very common presenting complaint
when somebody presents with PCOS.
- And assuming that a woman is doing
all these other things is paying attention
to the six pillars that
you talked about earlier,
diet, exercise, caloric
restriction, in some cases, right?
Not everyone needs to
be caloric restricted.
Stress, sleep, and sunlight, spirit.
Assuming that they're
doing all those things,
what other things in the realm of diet
or supplementation can
help them avoid PCOS
if they have subclinical PCOS
or they have not developed it,
but don't want to develop it?
'Cause it doesn't sound like a good thing.
- Yeah, so depending on where they are,
if they're very strong on the
insulin resistance spectrum,
then optimizing their body composition,
decreasing their body fat,
and treating that metabolic
syndrome can help.
So a lot of people ask,
well, does everybody that's on,
like does everybody need to
be on metformin that has PCOS?
Not necessarily, but
metformin is one of the tools
that can help with insulin sensitization.
Other tools that can help are inositol,
so myo-inositol is an insulin sensitizer.
Its cousin D-chiro-inositol is
a weak antiandrogen.
A lot of types of inositol
have both of those in it.
So depending on if
you're a female or a male
and you're on inositol, the
type of inositol does matter.
- Yeah, this is a very important point.
Just today I said I'm trying this new
supplement inositol for its role in
perhaps enhancing sleep even further.
My sleep's generally pretty good.
Lately it's been a little bit
off for a number of reasons.
So I took it for the
first time last night,
and I said, I thought it helped,
and just subjectively, and you said,
"What kind of inositol is it,
because inositol is a very
potent androgen inhibitor.
It turns out I was taking myo-inositol,
which is not an androgen inhibitor.
The other type that you mentioned,
which is an androgen inhibitor is?
- D-chiro-inositol.
It's usually in a ratio
of 1 to 25 or 1 to 40,
in a much lower amount
compared to myo-inositol.
- In a supplement or in the body?
- In a supplement to
help induce ovulation.
- But for women who
have PCOS who might want
to try and reduce androgen,
then they would perhaps want
to take a form of inositol
that reduce the androgen
receptor activity.
Correct?
- Yeah. They want both.
So if you're a woman
and you've ever talked
to your doctor about getting
on the oral contraceptive
or spironolactone, which
is also an anti-androgen,
but it happens to be a
potassium-sparing diuretic
blood pressure medicine as well.
D-chiro-inositol might be a better option.
DIM or diindolylmethane is another kind
of weak antiestrogen,
antiandrogen that a lot of
women should consider as well.
- You mentioned oral contraception.
I've done a few posts on these.
Let's just call them,
they really are perceptual effects whereby
it's been demonstrated in
humans several times now,
and what appeared to me
to be very solid studies
where women that take oral contraceptives,
there is both a shift in
their perception of men,
'cause these studies only
looked at heterosexual,
the sort of arrangements here,
where women who are on oral contraception,
because it blunts some
of the peaks and valleys
of hormone output,
no longer experience the
same peak and valleys
in their assessment of
other men's attractiveness.
So it sort of flattens their
perception, so to speak.
They still find certain men attractive
and certain men unattractive,
but the degree of difference
is kind of mellowed out.
And likewise, men,
these data say that men
perceiving women's attractiveness,
they still see women on oral
contraceptives as attractive,
but a woman taking oral
contraception eliminates
this kind of peak in her attractiveness
that men would otherwise perceive.
In other words, oral
contraceptives are changing
the way that we perceive each other,
at least in terms of these
male/female experiments.
What is going on with that?
Is that because oral contraceptives,
blunt the increase in
testosterone that occurs
just before ovulation,
or is it because of a complex cascade?
What is going on? I find this fascinating.
- Yeah, so there's
differences in how your,
and I wouldn't use the
word change necessarily,
but alter the severity or alter the
peak, as you said.
So just like TRT is not going
to change you as a person,
an oral contraceptive will
not change you as a person.
It will just change your day
to day peaks and troughs in
libido and attractiveness.
So one of the main effects
of oral contraceptives,
almost all of them have
a synthetic estrogen
and a synthetic progestogen in them.
One common type of synthetic
estrogen is ethanol estradiol.
There is another new synthetic estrogen
that's out there as well,
but that anecdotally,
that seems to have even more side effects.
So this ethanol estradiol
is 100 times more potent
than endogenous or bioidentical
estradiol in the liver.
So it binds to the estrogen
receptor in the liver,
and it's going to increase
sex hormone-binding globulin,
which secondarily, as you mentioned,
decreases your free testosterone,
and especially your free DHT.
So that little testosterone
hump that you get
when you're a female that's ovulating,
that's really flatlined and
it's a pretty insignificant difference.
It's not negligible,
but it's a little bit of a hump
and you have significantly less
of that when you're on
a oral contraceptive.
- And does that blunt the
associated increase in libido
that normally would occur from
that increase in androgen?
- Yes.
- Yeah. Interesting.
And what about other forms
of contraception, right?
'Cause there are, there's copper IUD,
there's various implants.
There's rings, there's a huge number
of different forms of these.
So what we're talking
about is, as I understand,
it is only the effect of
oral contraception that
impacts hormone output.
Is that correct?
- Yeah, there's a lot of
other effects as well.
For example, your choice
of synthetic progestin
will alter how high your
platelets and SHBG go.
It appears to be the higher your platelets
and the higher your SHBG,
the your higher risk of a blood clot.
So a lot of women know that if they're
on a oral contraceptive
and they're already
predisposed to a blood clot
or a venous thromboembolism,
in their vein they have a blood clot
in either their leg, or their lung,
then it can increase that chance.
So you can choose a synthetic
progestin that is not going
to have as high of a response,
but there's various pros and cons.
Some synthetic progestins are
weak anti-androgens as well.
For example, there's one known as Slynd,
which is made from spironolactone.
So some women are on
spironolactone and that as well,
which is made from spironolactone,
which probably isn't
particularly necessary
unless they need it for a
diuretic or a hypertensive effect.
- I see, I'm just going to
intentionally interrupt,
and I apologize,
but specifically because
I wanted to ask about,
there is this notion
that oral contraception taken
over long periods of time
can disrupt fertility in
ways that are independent
of just the age-related
decrease in fertility.
Is that true?
- It depends on what
you mean by a long time.
6 to 12 months, it's possible.
Past that, it seems very unlikely.
However, the persistently elevated SHBG
can be present for quite some time.
- Wait, so if a woman
takes oral contraception
for 6 to 12 months and then stops,
will she essentially be aware
she would've been anyway
in terms of her fertility at that age?
Or are you saying that it
can cause permanent damage?
- Her fertility would be equitable
as if she had never taken it
if she's certainly 12 months,
but probably six months off.
- And what if she...
I know of women that have
taken an oral contraception
for many years are, in addition
to the age-related decline
in fertility that occurs
that's inevitable,
of course the slope is going
to be different depending
on the individual,
but are they
quickening the transition to infertility?
- Probably not, you could make a case that
because they've been on
a oral contraceptive,
they may have been
slightly more predisposed
to insulin resistance
and/or lower lean body mass.
But that's probably going to
be a negligible difference
compared to their resistance training
and also their caloric restriction
or caloric maintenance so-
- And of course there are also
effects of having children.
- Yeah.
- Yeah.
Right, I mean on all
these parameters, right?
'Cause it's a major
lifestyle shift, right?
That obviously people contend with
and have since the beginning
of human time anyway.
I want to ask some questions
about male hormone therapy
and male hormones generally.
But before I do that,
I have a couple of burning questions
that I get very often that
I'm just going to insert now.
Marijuana, I've heard that
it can decrease testosterone
in men and women.
I've heard that it can
increase testosterone.
Alcohol, I think there's general consensus
that high alcohol intake,
high barbiturate intake does
in fact reduce testosterone.
What about modest increase of alcohol?
I'm not a drinker, so I'm not
asking these questions for me.
I don't smoke pot, and whatever.
I just never really liked
marijuana or alcohol.
They're not my thing.
But many people want to
know the answers to these.
And the data that I've
seen are very confused
and conflicting, so what about marijuana,
does it reduce testosterone to
a significant degree or not?
- Cannabinoids itself,
whether it's THC or CBD,
are not going to reduce
testosterone by themself.
If it's smoked marijuana,
then it's very likely to
increase your aromatase,
which increases your estrogen.
And that's going to,
it's aromatizing from testosterone.
So that is going to decrease testosterone.
When you have an increased
estrogen, like estradiol,
that's going to work on your pituitary
to make less hormones that
cause release of testosterone.
So you're going to have
less LH and less FSH.
So it's almost kind of like
opiates are well known to,
opiate agonists, they're
going to decrease LH and FSH
and subsequently testosterone.
Smoked marijuana will as well.
As far as alcohol,
high alcohol will decrease testosterone
as will any very potent GABA agonist,
whether it's a barbiturate,
or benzodiazepine, or
a non-benzo or alcohol,
they're definitely going to.
Moderate alcohol, I guess it
depends on what your definition
of that is.
The American Heart-
- I guess I'm thinking like,
some people I know that
don't seem to be alcoholics,
at least by my assessment,
will have a glass or two
of wine four nights a week,
which to me seems like
a tremendous amount,
only because I don't like alcohol.
I don't have a problem with
other people liking alcohol,
but I think for many people
that would be considered low
or moderate intake.
- Yeah, I would consider that low intake.
The American Heart
Association for men recommends
between one and two
drinks a day on average.
- They recommend it?
- So around, yeah.
So around one per week.
- Wait, so I'm making
my heart less healthy
by not drinking alcohol.
- Yeah, they recommend a very low amount
of alcohol intake for men.
For women, they recommend zero to one.
So that's kind of hard to
interpret, zero to one.
But the protective effect of alcohol,
especially if it's a red wine
with polyphenols in it,
outweighs the deleterious effect.
- Interesting, 'cause I've
seen some studies that point
to the idea that even
low intake of alcohol
over a prolonged period of time
might actually decrease brain volume
or at least volume of
particular brain areas.
But of course we don't
know the consequence
of decreasing the volume of
a given brain area either.
I mean, one can imagine
it's decreasing the size
of one's amygdala and
making them less stressed.
Although there's no
evidence to support that.
I've been told that I need
to drink many, many times,
but I always reply that I
don't need to drink anything
in order to speak my mind.
So again, individual differences.
Very interesting, so it sounds
like smoked marijuana may
in fact reduce testosterone
or at least increase the conversion
of testosterone to estrogen, correct?
- Yeah.
- Okay.
- And with alcohol and GABA agonists,
it's important to remember
that it shouldn't be daily.
So one drink of alcohol a day
is actually very mildly immunosuppressive.
So it's better to have two
drinks of alcohol one day
of the week and then two more drinks
of alcohol another day of
the week and then no alcohol
the rest of the time.
The same could be said
even for supplements
that have GABA in them.
A lot of sleep supplements
have gamma-aminobutyric acid,
which is GABA, so-
- Yeah, I occasionally take,
oh, sorry to interrupt.
I occasionally take 100
to 200 milligrams of GABA
in order to enhance sleep.
But I do it maybe every
third or four nights.
No more than three or four nights a week.
- Yeah.
- Yeah.
- That's perfect.
- Okay.
- So there's a lot of sleep supplements
that should not be taken daily
and GABA's one of them.
Another one of them is Trazodone.
And melatonin is kind of arguable
and it depends on the situation.
But in general, if you're
taking a sleep supplement,
it should not be taken every night.
- The sleep supplements that
I understand are okay to take
every night or nearly every night
are things like magnesium 3 and 8,
apigenin, if that's not true, correct me.
I certainly take them every night
unless I forget them back
home when I'm traveling.
- Magnesium's one of the exceptions.
L-theanine is also another exception.
- Great, well then at least
I haven't put anything
into the world that's
wrong in that category yet.
And hopefully I won't.
But if I do, I'll correct myself.
So let's talk about testosterone in males.
You see these headlines all the times now
that testosterone levels are dropping,
sperm counts are dropping.
Phenotypes of men are changing over time.
And I can't quite follow
the literature on that,
because obviously those are
hard controlled experiments
to do, because techniques
change over time,
and sensitivity of
techniques change over time.
But regardless, I'm aware
that a lot of people
are considering increasing
their testosterone by taking testosterone.
A few years ago that was
considered steroid use,
and it was really extreme kind of stance.
Nowadays it seems like there's
more discussion about it.
First off I'd like to know
does testosterone supplementation,
and here I'm talking about
prescription from a doctor,
does it make one more
prone to prostate cancer?
That seems to always be the
first question that comes out.
- Yeah, and there is a huge amount
of misinformation about this too.
So testosterone is not going
to cause a prostate cancer.
However, normal aging
causes prostate cancer
and testosterone will
grow your prostate cancer.
So if you're a 80-year-old
male and you have an autopsy
and there's at least say 50%
percent chance that you have
a prostate cancer, if
you're 90 or 100 years old,
there's at least a 90% chance.
So for humans with a prostate,
it's only a matter of time
until you get a prostate cancer.
So that begs the question,
do you want to take something
that's going to grow it
for sure once you have it?
So it's an individual assessment
and it's important to follow
things like PSAs as well.
- So a PSA of four or less, I mean,
ideally you wouldn't be at four,
'cause that's kind of the upper threshold,
is the simplest read out of whether
or not there's excessive prostate growth.
There's benign prostate hyperplasia
where the prostate is growing,
but it's non-cancerous, correct?
And then of course there
are the symptomologies,
like people have
challenges with urination,
they have sexual difficulties, et cetera.
I'm always struck by the correlation
that people draw between testosterone
and prostate health and the fact that,
or I should say the claim
that testosterone makes
prostate health worse.
Because if you think about it,
young males have high testosterone often,
if not always, or certainly often.
And you don't see a lot
of prostate overgrowth
and cancer in young males.
So something's going on here.
How should we conceptualize this?
- So if you have a PSA of 3.9
and you're a 25-year-old male
versus a 75-year-old male
and you have a PSA of 5.9,
the 3.9 PSA is significantly
more concerning.
So think of your prostate
as taking cumulative damage
from, not only testosterone,
but also estrogen and also growth hormone.
So that's why obese individuals
have higher incidences of
prostate cancer as well,
is because they don't have
those cell checkpoints
where your immune system takes
a second and says, all right,
stop replicating as fast prostate cells.
Let's see if there's any atypical ones
and then it finds those
and it prevents them from reproducing.
That's why immunotherapy
in cancer is so promising
is because they can target
these certain things.
So the older male is going to have
that cumulative damage happen already
and arguably prostate cancer is a normal,
with aging, fast aging is abnormal.
Very slow aging is normal.
There's a fine line to
walk between those two.
But there's a lot of
things that can be done
to decrease the turnover,
decrease the inflammation,
and decrease the congestion
of the prostate over time.
There's also a lot more than
just PSAs that can be done.
There's prostate MRIs and things like that
that can look at the structure
and the function of the prostate.
- So what should every male do
to maintain the health of their prostate?
And I realize that younger males
probably aren't thinking about it at all.
Although it seems like
nowadays I get these kind of
what I call cryptic questions.
I think women are more comfortable talking
about their hormone and sexual
health because of they cycle,
because of menstrual cycles.
They're used to fluctuations
that sort of give them
the experience of what it's
like to have different levels
of progesterone, estrogen,
testosterone, et cetera.
But I get these kind of
cryptic questions often
in my direct messages
where what I think people are asking is,
is there something wrong with my prostate?
What should I do for my prostate?
These are often indirect questions
for other aspects of their
life where they're suffering.
And I don't say that ingest.
I think more direct
discussion would be great.
So what should all males do
to maintain prostate health
throughout the lifespan?
- Maintaining prostate health
can be looked at similarly
how you can maintain a good
natural optimal testosterone.
So you look for things that can hurt it.
You don't necessarily look for one thing
that can improve it or boost it.
So for young males, those are prostatitis,
so it goes hand in hand with epididymitis.
So different infections of the prostate.
The younger the male is,
the more likely it is related
to something that could
be sexually transmitted.
But another very common cause
is what we call gram negative
and anerobic bacteria.
The prostate is right
by the end of the colon.
So if you have chronic constipation
or if you have colitis or if you,
even just an E-coli
overgrowth in the colon
is very likely to cause an infection
of the prostate as well.
- What should males do to prevent that?
- Have a diet that has good,
healthy prebiotic fiber,
probiotics as well.
Make sure that they're having
regular bowel movements,
that they don't have chronic constipation.
Have good sources of dietary fiber,
which is also as soluble fiber,
and enough insoluble fiber.
Most people get enough
insoluble or non-dietary fiber.
So that can help prevent the
chance of diverticulitis,
which is another type of infection.
It can also decrease the chance of colitis
and decrease the chance of
prostate infections as well.
- Are there any foods and/or supplements
that men should take or avoid?
What about, you hear
or about saw palmetto,
yeah, supplements for,
or supplements that support
or cause issues for the prostate?
- Yeah, if there's a strong
genetic predisposition
to enlarged prostates,
or even just really early
prostate cancers that grow fast,
then they could consider
taking saw palmetto
or even curcumin as an anti-androgen,
as long as they're able to tolerate it.
It's an individualized basis
and depends on their history.
As far as making sure that
their prostate is not congested,
there's an interesting
correlation between having girls
and having prostate cancer.
- Having girl offspring?
- Yeah.
- So if your offspring are females,
then you're slightly more
likely to have prostate cancer.
There's hypotheses that link
estrogen to prostate cancer
rather than testosterone.
So if you have hypoestrogenism,
your prostate has more atypical cells.
In general, the higher
your C-reactive protein,
which is the general marker
of inflammation in your body,
we call it CRP, and the
test order is hsCRP,
or high-sensitivity CRP.
If your CRP raises up very high,
if you have an autoimmune disease,
like if you have a Crohn's
flare or if you have lupus
or an infection or a sexually
transmitted infection,
or even a colitis, or even the flu,
your CRP is going to raise significantly.
- That you would detect in a blood test
of course.
- Correct.
Yeah.
- Yeah.
- So you want to get a baseline CRP
when you haven't had any
of those things recently.
And if your CRP is higher,
you also have more female offspring.
If your CRP is higher,
then your reactive oxygen species,
which are causing mutations
and atypical cell turnover
in the prostate are also likely higher.
So you want to keep a very low CRP.
- Interesting, and what about blood flow,
and pelvic floor in general?
We should probably do a whole
episode on pelvic floor.
There's so much interesting
data coming out of
the fields of clinical
and research urology.
I realize it's kind of the Netherlands
of biology and medicine.
People probably aren't
thinking so much about this,
but pelvic floor is obviously a confluence
of a ton of of vasculature, of nerves,
and of course the prostate resides there.
And of course the genitals
reside there as well.
So I would imagine that
one of the six pillars,
exercise, being able to
maintain adequate blood flow
to those regions is key.
What about just postural things?
People sitting too much,
not hydrating well enough,
you mentioned avoiding constipation.
What are some other things,
including medications that can
serve to support the prostate
over time and maybe even
support pelvic floor in general,
both in males and females over time?
- Absolutely, and this is something
that's rightfully getting
more and more attention.
The way I explain the pelvic
floor is your abdominal cavity,
which includes your
peritoneum or where most
of your organs are, your
retroperitoneum, your pelvic space.
Think of it as a box.
And your abs are the front of the box.
Your back muscles are the back.
Your diaphragm is the top of the box.
And your pelvic floor,
that's where your port
is to the outside world.
Especially important,
it has muscles as well.
And you can do exercises.
Pelvic floor physical
therapists are becoming more
and more utilized,
especially after childbirth,
but in other situations as well,
including by men getting
care from urologists.
So you want to both strengthen
that pelvic pelvic floor
and make sure that the
tubes that are docked
to the outside world
are working well enough,
but they're not too loose.
They're not working too well.
So there's a lot of medications
that can be positives
or negatives for your pelvic floor.
We kind of talked about your gut
and colon health in general.
As far as your prostate health
and as far as your bladder
and urinary system health,
you think about a couple
different classes.
So you have your phosphodiesterase.
You have your tadalafil.
Basically this is going to
help decrease congestion
in the prostate.
A lot of people take it for ED,
but it can actually
help you decrease your-
- Could you define that?
- A lot of men take to
tadalafil, generic is Cialis,
has a much longer half-life
than Viagra or Levitra.
Its half-life is almost a day.
So you can take a very low dose of it.
Instead of taking 20 milligrams,
you take two or two and a half milligrams.
- So you're saying that
a lot of men take it
for erectile dysfunction?
- Yes.
- But that at it at lower doses,
it may have served purposes
for prostate health,
independent of erection?
- Correct, the most common
scenario is if a male
is waking up twice at
night to pee, on average,
it'll cut that down to once.
So if they're waking up
at four times at night,
then it can cut that
down to twice at night,
just because you have easier blood flow.
We used to use other
medications like Flomax,
which is tamsulosin.
That's an alpha antagonist,
so it basically binds to a
receptor in smooth muscle,
and it helps relax that.
There's several other alpha antagonists.
And then you also have your medications
that are hormonal like finasteride
that a lot of people
take for prostate health
to decrease the enlargement
of the prostate.
The periurethral area,
or periurethral lobe,
there's several lobes of the prostate,
that tends to be especially
enlarged in cases of BPH and-
- BPH?
- Prostate hyperplasia
or an enlarged prostate.
And if you are able to shrink that area,
then at that point, it's
just a plumbing problem.
And the urine is able to get by easier.
- Yeah, my understanding is
that now there's a growing,
I don't want to say a movement, [chuckles]
but the idea of taking very low dose,
like 2.5 milligram or
5 milligram tadalafil,
even daily is becoming pretty common
for many men who do not
have erectile dysfunction,
simply to either maintain
or enhance prostate health.
Is that correct?
- Yeah, that's correct.
- And do you see any negative
effects of doing that?
- There can be negative effects.
It can lower blood pressure.
So theoretically it can
increase your chance
of vasovagal syncope.
A lot of people take it
as a alternative to pump,
because it kind of works
similarly to citrulline,
or different pump products in pre-workout,
and it can certainly help with that.
But if you're about to go do a deadlift
where you might pass out anyway,
it can certainly increase
the chance of that happens,
because you don't have
that compensatory exercise,
hypertension response.
- Could someone just take
it away from exercise?
- They could, if you took tadalafil,
then that's going to be,
has a long half-life.
Whereas Viagra and Levitra
is just a few hours,
tadalafil almost today.
Some interesting studies on
Viagra have been done as well.
It can potentially alter your
rays and cones in your eye.
So the usual recommendation
for pilots that need
to have red-green discrimination
from very long distances
with very small indicator lights
is to not take Viagra.
So I usually say
if you're a pilot and
that's your profession,
perhaps hold off from that for a while.
There's also studies with
Viagra that significantly,
which is also known as
sildenafil as the generic now,
it can increase eyebrow hair growth.
So potentially what it
does is it helps vasodilate
and relax the veins,
especially in older men.
And when those veins are relaxed,
you have better blood flow.
That's one of the proposals or theories
behind why older men get the
androgenetic alopecia more.
You're having less
blood flow in the scalp.
So theoretically it can
also help prevent that,
but it's not going to-
- So in theory,
increasing blood, oh,
because it increases
blood flow systemically
throughout the body?
- Yeah.
- Not just in specific tissues.
Well, I find it incredibly
interesting that, yeah,
there are these online
forums building up now
around low dose tadalafil,
daily use of low dose tadalafil, again,
not for sexual or erectile dysfunction,
but for sake of longterm prostate health.
Is there any reason why women might want
to take low dose tadalafil?
- tadalafil is also a weak
androgen receptor sensitizer,
kind of like L-carnitine,
where the density of the
available androgen receptors
to bind increases slightly.
So there could potentially
be a benefit from that,
but most of the time it's used in men.
- Very interesting, we
haven't really talked
about testosterone and
optimizing testosterone in males.
Assuming someone is paying
attention to the six pillars,
there's kind of a gap as, I see it,
between doing all those things and TRT,
hormone replacement therapy.
And again, the R, the replacement in TRT
is a little bit of in quotes nowadays,
because a lot of people
who have testosterone
in that 300 to 900 nanogram
per deciliter range opt
to take low dose testosterone anyway.
My understanding is that
there have been some new kind
of movements in this area
toward, for instance,
not doing big, large doses
injected infrequently,
but rather low doses quite frequently,
obviously prescribed by a doctor,
monitored by a doctor, et cetera.
Is that generally what you
like to see in your patients
if they're going to take this route?
- If they're a hypogonadal patient
whose benefits outweigh risks of TRT,
then you want to have a
nice even steady state.
It's not going to be exactly the same
as producing pulsatile
testosterone release endogenously
from your own body.
When you have a steady state,
you don't have a peak or a trough.
And when you have a peak,
that's when the antigen
receptor gene is overactive,
that's when you get more
erythropoietin or EPO release,
and that leads to a lot of the
side effects of thick blood,
so higher hemoglobins, and hematocrits.
And then when you have a
crash, you don't feel good.
So it's definitely not optimal.
There's a lot of ways to get around this.
So when you're doing
testosterone replacement,
if you're someone that needs it,
you can have different types of esters,
or you could do topical testosterone.
So the Ester is basically something
that's attached to increase
the biological half-life.
The most common ones are
cypionate, enanthate,
there's also a very
short-acting propionate,
which has almost no clinical relevance.
And there's also very long-acting ones,
decanoate, and undecanoate,
and different mixtures of all those.
So if you're someone who
has a very, very low SHBG,
you're going to have trouble of regulating
your serum testosterone in the long run.
If you do it topically,
then the testosterone is
absorbed, hopefully bound to SHBG,
and then a lot of times
you reapply twice daily
or once daily, but you
have lots of variations.
So for most people,
especially for people
who can't absorb it well,
that's not going to be a great option.
So injections would be preferred.
Most people end up injecting,
because they have either
side effects from too high,
too low, or just too much of a varied dose
when they do topical.
There's also a capsule with a
special lymphatic absorption.
So it's not being absorbed
through the liver,
it's not hepatically metabolized,
but it's absorbed through the lymph.
And it's essentially
testosterone undecanoate,
and then put into a capsule.
And that's taken twice daily.
It has fairly steady half-lifes,
but you have to take it at
specific times of the day.
So that being said,
and it's new enough to where
there isn't a huge amount
of data on it, but it is FDA approved.
So it is brand name now.
it's called JATENZO.
But the injectables in general,
the lower your SHBG, the
longer of an ester you want,
because when you inject it,
whether it's intramuscular
or subcutaneous,
just talk to your doctor about the risks
and the benefits of those.
Subcutaneous has slightly
longer active half-life,
because the esterases take longer to reach
that supinate or an estered clavate.
So most men, a lot of
people ask me about like
what a usual dose is.
For most people, it would
be a total of about 100
to 120 per week for an
actual replacement dose.
- Milligrams?
- Milligrams.
120 to 100 milligrams per week
administered two to three times per week.
- And you're not, so you're
saying dividing that into two
or three, right?
'Cause I'm sure a bunch of
people out there are thinking,
oh yeah, 103 times a week,
which is actually quite a high dose.
Yeah, there really does seem to be a shift
toward spreading these dosages out into,
dividing them into two
or three smaller doses.
And then along those lines,
5, 10 years ago,
it was common to hear
about inhibiting estrogen
through aromatase inhibitors.
Nowadays you hear, and I think it's true,
at least by my read of the literature,
that inhibiting estrogen
can disrupt brain function,
can cause connective tissue issues,
and even can cause reductions in libido.
So a lot of people think they estrogen,
if you crash estrogen, that
basically libido goes up,
but actually the opposite is often true.
You don't want estrogen
too high or too low,
is that correct?
And for that reason,
do you shy away from people
taking aromatase inhibitors?
- Yeah, very few people truly
need aromatase inhibitor.
There's almost always
lifestyle interventions.
It can just depend on which gene,
how active your aromatase gene is.
Some people's aromatase
gene is very active.
A lot of times these individuals
have pubertal gynecomastia,
which is breast tissue growth in males,
even despite no other risk factor.
- Even if they're lean?
- Some people get it if they're lean.
- I remember growing up-
- It's possible.
- There were a few kids
that got mild cases
of gynecomastia that were transient.
Like it's sort of like
they developed gynecomastia
and then it went away.
- Often it's unilateral on one side too.
So growth hormone a lot of
times is the fuel to that fire.
- Oh, interesting.
- Yeah.
- Yeah, there were a couple of kids.
I mean, they took some
teasing 'cause back then,
there wasn't online
discussions about hormones
and things like that, but
then it would seem transient.
And they were,
the people I'm thinking of
were actually lean individuals.
So they weren't overweight,
which of course can cause gynecomastia,
because adipose fat tissue
can convert testosterone into estrogen.
So it sounds like,
except in special cases,
that avoiding aromatase inhibitors
is probably going to be a good idea.
- Yeah, there's several other ways
that you can control
your estrogen and keep it
at a healthy level, which
you do have to check.
There's a lot of patients who assure me
that their estrogen's going to be sky high
and it's actually very low and vice versa.
But calcium D-glucarate is a supplement
that can help with estrogen control.
- What's a typical dosage
of calcium D-glucarate?
- 500 To 1,000 milligrams.
- But is there the risk
that if someone's estrogen
is in normal range and
they take the supplement,
that their estrogen will go too low?
Is it that potent?
- It's not that potent.
It's not near as potent
as an aromatase inhibitor.
So it helps with excretion
and also the sensitivity
of the estrogen receptor itself.
And it kind of like helps outcompete it.
Some people will also take DIM
or different cruciferous vegetable,
they get 'em from cruciferous
vegetables like kale but,
or broccoli and that
is both an antiestrogen
and an antiandrogen.
So if you're on TRT and you're on that,
then you're probably just on too much TRT.
- Yeah, I remember a few
years ago I had a friend,
and it truly is, it's not
like I have a friend thing,
'cause I'm very cautious just about
which supplements I take.
I think people might get the impression
that I'm very cavalier
about this, but I'm not.
I always alter one thing at a time.
I talk to physicians.
What I suggest other
people do I actually do
and have done for a long period of time.
And I recall wanting to take
DIM, 'cause I thought, well,
back then you hear, okay, reduce estrogen.
My estrogen levels weren't out of range,
so they were fine, but I thought, well,
what would the experience
be of bringing those down?
But someone I know is quite
informed in this area said,
yeah, exactly what you said,
which is that DIM can reduce estrogen,
but also testosterone.
So I just never opted to try and take it.
I do want, we're sort of
airing in this direction,
but we went straight from
the six pillars to TRT
or to what some people
now call sports TRT,
which is basically code language
for saying taking exogenous testosterone
even though one doesn't
need it to get into
a semi-super physiological
range or a high end,
like 900 to 1,000 nanogram
per deciliter range.
And people always point out,
I should mention that, oh,
well in certain countries,
the high end range is 1,200
nanograms per deciliter.
In the US, it's 900.
And so if you're 1,200, are
you really super physiological?
All that aside,
I neglected to ask about
that gap in between
where individuals could
think about supplementation,
meaning non-prescription approaches
to increasing testosterone,
and here we should probably
also talk about things like,
is it true that ice baths
increase testosterone or not?
Lifestyle factors that
go beyond the six pillars
for increasing testosterone.
If you could comment on
those, that would be terrific.
Supplements that are useful.
And it'd be wonderful if you could mention
where some of these same practices
and supplements might be
useful for women as well as men
to increase testosterone
for all the reasons we
talked about earlier.
- Yeah, so this is where
a true individualized approach comes in.
When you're talking about what
dose of TRT you should be on,
one thing to keep in mind is
the law of diminishing returns.
Quality of life is a subjective thing
and it's different for each person.
So some people are more willing to give up
a little bit of athleticism
or body composition.
Some people are more willing to give up,
or not willing to give up
libido or sexual health.
And as we mentioned earlier,
everybody's androgen receptor
is less or more sensitive.
So you can make a case that if
somebody's androgen receptor
is half as sensitive as somebody else,
the person with the less
sensitive receptor does need
a level of 1,000 or 1,200.
There's no great way to know that.
And you can alter the sensitivity
of your androgen receptor
with things like L-carnitine
and tadalafil as mentioned.
- And we'll definitely
come back to L-carnitine,
because I'm really intrigued
by the data on L-carnitine,
both for women and men
in terms of egg quality,
sperm quality, fertility,
and a bunch of other interesting effects.
So we'll come back to L-carnitine.
- But a lot of how you feel,
the biofeedback or subjective,
I feel like this, comes from the ratio
of your androgens to your estrogens.
And a lot of that is lifestyle.
So if someone's also on hCG,
that could upregulate aromatase as well.
- hCG, you might want to just,
human chorionic gonadotropin?
- [Kyle] Yeah.
Used to be found in pregnant,
is still found in pregnant women's urine.
- Still found in
pregnant women, yeah.
- But used to be,
believe it or not,
there was a black market
for pregnant women's urine
before this stuff was
developed synthetically.
So in other words, what
we're saying is men typically
would buy pregnant women's urine
through black markets
in order to get the hCG
in order to get the
testosterone-enhancing effects of hCG.
So in other words,
men were using pregnant
women's urine for hCG.
I do not want to how they
got it into their body.
Let's just skip to what you
were going to say next instead.
- Yeah. So that's hCG.
There's a lot of other things
that upregulate estrogen.
Alcohol significantly increases aromatase.
So if you're very sensitive to estrogen,
then you probably shouldn't even consume
two glasses three times a week.
High fat meals also upregulate aromatase.
So if you're on a ketogenic diet,
but you have hyperestrogenism,
then you should take
care with that as well.
- All kinds of fats or
just saturated fats?
- I'm not sure if it's
just saturated fats,
but fat definitely increases,
both fat and your body and consumption
of a high amount of calories
increases aromatase.
- So the it's the ratio of
testosterone and estrogen.
I don't want to break your flow,
but since we're talking
about fat, I have to ask,
since estrogen and testosterone
are both synthesized
from the cholesterol molecule,
I've heard that ingesting
some amount of saturated fat
can be useful because of
the way that cholesterol
can serve as a precursor
to these molecules.
Now I once said on a podcast
that I like butter so much
that I occasionally eat pats of butter.
Somehow that got misinterpreted to mean
that I eat entire many pats of butter.
I'm saying like one or two
pats of butter here and there,
and I have no guilt or shame about it.
My blood lipids are in great
shape also, so I feel good.
But is it possible that people
who are ingesting too
little of saturated fats
could directly or indirectly reduce
or somehow disrupt the
proper ratio of testosterone
to estrogen in men and women?
- It's theoretically possible,
but it probably doesn't
happen in developed countries
just like it's theoretically possible
to have not enough omega-6 fatty acids,
but that probably does not
happen in developed countries.
- So I don't need the butter pats,
but I'm going to do it anyway.
I'm just curious.
- Yeah.
- Okay.
- Grass-fed butter has good
omega-3 content as well.
So grass-fed foods in general.
It's not the end all be all
and everybody doesn't
need grass-fed foods,
but they are one of the only
sources of healthy trans fat.
So a naturally occurring trans
fat comes from ruminants.
So ruminants, think of like cows and
the rumination in the different stomachs
can change your omega-3 and omega-6
to trans-linolenic and
trans-linoleic fatty acids.
- Which are healthy for us.
- Yeah.
So it's actually omega-3s and omega-6s
that just happened to have a
trans instead of cis-isomer.
- And these healthy
trans fats would be found
in ruminant cheese and milk and butter
from ruminants and the meat-
- And the meat.
- And the meats?
- Yes.
- And for people who are following
a purely plant-based diet
or mostly plant-based diet,
are they at risk of not
getting enough of certain types
of fats or other nutrients to
maintain that healthy ratio
of testosterone to estrogen or not?
- If they're a vegetarian,
they're probably not at risk.
If they're a vegan, they
very well could be at risk.
Most vegans are aware of this very acutely
and they'll supplement with
algae or they'll supplement
with other sources
of healthy fats.
- I see, so the takeaway
that I'm drawing from this
is that less so than
getting saturated fat,
it's key to get these healthy
trans fats from ruminants.
- [Kyle] Yes.
- Or the food products of those ruminants
as well as to get proper
amounts of omega-3s.
- Yeah, and to be clear, you
don't need any trans fats.
It just happens that those
omega-3s and omega-6s
are in a trans-isomer.
- I see, okay, so that's nutrition.
What other supplements can
support healthy testosterone
to estrogen ratios?
- Anything that alters aromatase
can support healthy
testosterone to estrogen.
And your testosterone to estrogen ratio,
think about it as how
much estrogen activity
do you have at the beta estradiol receptor
and your alpha estradiol receptor.
- How would I know that?
- So [chuckles] it's hard to tell,
but depending on what you're eating,
if you have a lot of plant-based
diets or polyphenols,
many of these are beta
estradiol receptors.
People know about Turkesterone
and also Beta-Ecdysterone,
which are two ecdysteroids
that are beta estradiol receptor agonist.
So they activate the
beta estradiol receptor.
So if you have a very low
amount of estrogen naturally,
you're probably a better candidate for it.
- For taking Turkesterone or ecdysterone?
- Yeah, ecdysterone.
- I've never tried them,
but I know my understanding
is that they work tremendously
well for some people.
- Yeah.
- And not at all for others.
And so one just simply has to try.
But in promoting the activity
of this estrogen receptor,
is there a risk that
Turkesterone or ecdysterone
could cause some of the
quote/unquote problems associated
with increasing estrogen activity,
like reduced libido, water retention?
- Water retention, yes.
Reduced libido, probably not.
Closing growth plates in the bone, no,
because that's the
alpha-estradiol receptor.
- I've talked before on a couple
of podcasts about tongkat ali,
which is Indonesian herb, I guess,
is also made and found in Malaysia.
But it seems to be the
Indonesian variety of tongkat ali
that's most effective for potentially
for reducing sex hormone
and binding globulin
and thereby freeing up testosterone.
Whether or not the effects
are through that pathway,
through another pathway,
a lot of people report
improvements in things like libido
and maybe androgen-like phenotypes, right?
Feeling more vital, et cetera.
And of course, some of that
could be placebo, correct?
But what are your thoughts on tongkat ali?
And please challenge my
statements about tongkat ali
if they're incorrect.
I'm not looking for validation here.
I just really want to know
what your thoughts are on it.
Do you ever recommend
it to patients, when?
Men, women, one or the other?
- Yeah, so tongkat ali or longjack
has multiple mechanisms of action
and there have been several
placebo controlled studies on it.
Some of them show decrease in SHBG,
at least one of them did
not show any change in SHBG.
However, it does act on
aromatase very weakly.
Probably not so strongly
that you would have
to be concerned of hypoestrogenism.
- So it reduces aromatase and thereby
can reduce estrogen.
- Correct.
- Okay.
- It's also a weak, it's not SERM,
so it's not a selective
estrogen receptor modifier,
but it's probably a weak,
it's probably an ERM as well
or a non-selective
estrogen receptor modifier.
And that should help
with decreasing negative
feedback inhibition
of estradiol in various locations
and also increasing testosterone.
- Interesting, yeah,
the dosage that I've been
using for years now is,
it's 400 milligrams taken once a day,
typically early in the day,
'cause it can kind of have
a mild stimulant effect, very mild.
And I know that some of
the products out there
recommend dosages that are much higher.
Anytime I've taken more than
400, I don't feel very good.
I don't know how to describe it other than
it's just a little overly
stimulatory in terms
of makes me kind of,
it's like drinking too much coffee.
- [Kyle] Yeah.
- So that's interesting.
And so would women ever
want to take tongkat ali
for any reason?
- Yeah, absolutely.
So there's a lot of women
that have hyperestrogenism
and unlike adrenal fatigue or andropause,
there's actually ICD 10
codes for hypoestrogenism.
- ICD 10 codes?
- Yeah.
- That's doctor speak, right?
- Yeah.
- Okay.
- So there's codes
to where your doctor
can actually diagnose you with something.
So if you go to your doctor and you say,
I have adrenal fatigue, they
can't diagnose you with that.
Or if you say I have andropause,
they also can't diagnose you with that.
But if you say you have hypoestrogenism,
the most common complaint
that comes with it
is endometriosis, which is
overgrowth of the lining
of the uterus.
And those people could potentially,
I think, that's one
area where we might see
tongkat supplementation more and more,
because not only does
it decrease aromatase.
Like we mentioned,
testosterone in females is higher
than estrogen in females.
So a lot of females get estrogen
from aromatization as well.
Peripheral estrogen is
sometimes what we call it,
because it's not directly
produced in the ovaries.
But they could be good
candidates for tongkat
if that's the case.
- Very interesting and my understanding
is that people should
be looking for sources
of Indonesian tongkat ali in particular.
- Correct.
- Right.
- Another interesting
application is essentially a,
I'll call it a PCT,
but essentially-
- What that means is?
- PCT means, I'll defined
it as post-cycle therapy.
- Physicians love acronyms,
scientists love acronyms,
military love acronym, but we, yeah.
PCT, post cycle therapy, so
this would be people coming
off hormone therapy or steroids.
- This would actually be for
women that are coming off
of their birth control pill,
because perhaps it can help
lower that SHBG back to normal,
which is sometimes persistently elevated,
and then it can help prevent
the subsequent
hypoestrogenism that happens.
- Does tongkat ali need to be cycled?
When I first started taking
it, I would cycle it.
I would do a few, three, four months,
and I would take some time off.
Now I've just been taking
it continuously for years.
- [Kyle] Yeah.
- And I should say I do blood work
to check my liver enzymes
and everything else and
I don't see any reason
for me to cease taking it.
- Yeah. Probably not.
There's been human studies
on both tongkat and Fadogia.
And full disclosure,
I did help design Derek's new
testosterone optimization supplement,
which has both Fadogia agrestis
and also tongkat ali in it.
- Yeah. Let's talk about
Fadogia separately in a moment.
But let's say someone is
only taking tongkat ali
for whatever reason, do
they need to cycle off?
- Likely not, but I would just to be safe,
because it does both affect your aromatase
and it's an estrogen receptor modifier.
- And what would be a
reasonable cycle off?
So how long to take and how long to stop
before taking it again?
- Yeah, there's a couple
different protocols
that you can do,
but 11 months on, 1 month off for tongkat
is pretty reasonable.
Now I guess this is,
we'll talk about this later too,
but if it's combined with Fadogia,
the protocol that I would
do is three weeks on,
one week off.
- So that's tongkat ali.
But I'm curious what your
thoughts are on Fadogia agrestis,
this Nigerian shrub or this
extract from Nigerian shrubs
that at least in my experience,
in my read of the literature,
has the potential to increase testosterone
and probably other hormones as well
by way of increasing luteinizing hormone.
Something that we haven't
really talked about much
up until now.
What are your thoughts
about Fadogia agrestis?
What are your ideas about
the proposed mechanism
or mechanisms and where
might this be useful
for people on or off
hormone replacement therapy?
- Yeah, Fadogia agrestis
has just reached a point
where we have enough evidence till we know
it probably helps both with
luteinizing hormone release,
which stimulates Leydig
cells in the testes
to produce more testosterone.
And probably with LH receptor sensitivity
as well, which is a good
combination of the two.
It does come from the Nigerian shrub,
but there is not quite
enough evidence for me
to be able to say
it's safe for someone to
take this all the time,
which again, full disclosure,
that's why I recommended that we
recommended for people
to cycle this supplement.
So three weeks on, one week
off, that's likely safe.
The only toxicity studies in general are
in rats and in humans,
it looks quite safe.
- My understanding is
that the toxicity studies
in rats showed toxicity
to the testicular cells,
so that's certainly concerning,
but that the dosages that
were used or translating
the dosages used to humans would lead
to a situation where
the dosages that humans
would have to take would
be very, very large.
So the amount of, I no
longer take Fadogia,
but I took it at 600 milligrams
per day for a long time.
And I ceased taking it
because I was experimenting
with other things and I didn't
want to confound those things.
Not because I had any
negative side effects.
In fact, I was monitoring blood work,
and other biological parameters
that would've told me
if there was testicular
toxicity, and there wasn't.
Let's put it that way.
- Yeah. I think it's extremely safe.
And I'm just not convinced
that there's enough overwhelming evidence
for longterm consistent administration.
- So do you recommend this to
people who are not taking TRT
and do you recommend to men and women?
- Yeah, so if you have a really high LH,
then there's probably a gonadal issue,
whether it's heat damage to
the testes, a varicocele,
a history of testicular cancer
where your LH is going to be higher.
So if your LH is already very high,
increasing it even more is
probably not going to help.
However, if your LH is low,
then obviously try to find out is it low?
Is it deficient or is it
just a little bit low?
If it's low and you don't
have an issue with prolactin,
you don't have an issue with
opioid receptor antagonism,
and naltrexone can actually
potentially help antagonize
that to increase LH as well,
especially in people
recovering from opiates
or likely even alcohol.
So you're looking for a
subclinical secondary hypogonadism,
which is essentially, just
think of that as low LH.
So in people with that lower
LH and their estrogen is fine
and their prolactin is fine,
then Fadogia is a
particularly good option.
- Interesting, so three weeks on,
one week off for 600 milligrams Fadogia,
400 milligrams tongkat
ali, Indonesian tongkat ali
could potentially you be good.
And of course, everyone
should always check
with their physician,
clear this, do blood work, et cetera.
I always say we don't just
say that to protect us.
We say that to protect
you, meaning the consumer.
And it's very, very important.
You don't want to get,
you don't want to fly blind
with any of the stuff.
You want to do blood work, right?
- That's the catch-22 with supplements
is most of them are
safer than medications,
but the only difference
between them and a medication
is one's prescribed and one's not.
- And oftentimes with supplements,
it's unclear whether or not
what's listed on the bottle
is actually what's in the bottle but.
- Yeah.
- But I think there are a
number of reputable brands now.
The other supplement I want to talk about
in terms of testosterone
augmentation is boron.
What is boron thought to do?
Does it actually do that?
And do you ever recommend boron?
- Yeah, so boron is actually an element.
And you can find it on the periodic table.
It's more plentiful in rich soils.
So frequent farming can
deplete the soils of boron.
It's very plentiful in
the Mediterranean area
like Greece and Turkey,
so a lot of people will
just eat dates or raisins
that are grown there.
- I thought you were going
to tell me people eat dirt,
but there are people
who eat dirt.
- There are people
who eat dirt.
- And there's a phenomenon
called pica, right?
Where people in a, and that's
not a good thing, they-
- Often assign a iron deficiency.
- Okay, but they're
eating grapes and dates
that were grown in soil that
has high amounts of boron.
Is that right?
- Yeah.
Yep, so boron can help regulate SHBG,
but its effect is mostly acute.
So it's unlikely to have a bad effect,
so a lot of people take boron
because it's probably not going to hurt
and it will lower SHBG even if it
is for a short period of time.
So I guess you could make a
case that maybe cycling boron
can help too.
- What sorts of dosages
are useful for boron supplementation?
- Three to six milligrams
once to twice a day.
- Oh, interesting, so that's
higher than the amounts
that I've been taking.
I've long been doing this
cocktail of tongkat ali,
again, I stopped taking Fadogia,
but for a long time
with Fadogia, and boron,
I think it was two to
four milligrams per day,
but maybe I could afford to go higher.
Although my blood work is
where I want it, thankfully.
So circling back to Fadogia.
Fadogia was attractive
to me as a supplement,
because I saw increases
in LH, testosterone,
and free testosterone.
My estrogen stayed in check,
but I also did not see
a down-regulation of LH
when I would cycle off.
Whereas with hCG, human
chorionic gonadotropin,
which does now arrive
in forms not from pregnant
women's urine only,
but the synthetic forms
that people inject,
that, as I understand,
it can actually suppress
endogenous hormone output
if one takes it for a long period of time.
So why would a man or
woman want to take hCG?
And what are the potential risks
and benefits of taking hCG?
- Yeah, so hCG or human
chorionic gonadotropin
is actually very similar to TSH.
- Thyroid stimulating hormone?
- Correct, so when a woman is pregnant,
she produces more hCG,
especially in the first trimester.
When you take a pregnancy test,
whether it's qualitative or quantitative,
you see the hCG rise,
and it actually doubles every 48 hours.
So if you're five weeks pregnant,
you can get a hCG level.
And then two days later,
five weeks and two days,
you can see your hCG,
and maybe it went from 500 to 1,000.
So it precipitously increases.
It does a few things.
One thing is it prevents hypothyroidism
or hypothyroxinemia of pregnancy,
which is one of the most
common causes of miscarriage.
It's also why if you are,
if you have hypothyroidism
and you get pregnant
in the first trimester,
you want to increase
your dose from 25 to 40%
to keep your free T4
high as much as possible.
And the reason why you have to do that
as opposed to somebody who
does not have hypothyroidism,
is if you have hypothyroidism,
then likely your thyroid will not respond
to either TSH or hCG.
So the increased hCG does
not compensate for that.
So if you take hCG,
then it can potentially
improve your thyroid function.
So that along with selenium
are likely the two best things
that you can do for thyroid health.
- hCG and selenium?
- Yeah.
- Well, I definitely make
sure I get enough selenium
by eating three to five
Brazil nuts per day.
- Yeah.
- Which I very much enjoy
the taste of also.
Who should take hCG and can hCG suppress
one's normal luteinizing hormone output?
- Yeah, it suppresses LH
in a dose-dependent manner.
So the higher the dose of hCG you take,
the more it suppresses LH.
A common dose for fertility,
fertility is usually
why hCG is prescribed.
- In men or women?
- In both, is 10,000 IUs
all at one time, which is quite a bit.
- That's a tremendous dose.
- Yeah, in fact, some formulations,
some brand names of hCG
come in autoinjector pins
to where you cannot even
dose lower than 5,000 units
at a time.
- Wow.
- Yeah.
- But I know a number
of people who take hCG
to maintain testicular function while
on testosterone therapy or
augmentation of some sort.
Does it work to do that?
- Yeah, some people
are on hCG monotherapy.
It can be slightly better on your lipids
than being on TRT.
- Oh, so people are using hCG alone
as a kind of
neither sort of a indirect
hormone augmentation.
- Yeah.
Some clinics advertise it as
a non-suppressive alternative
to TRT, but it is suppressive of LH.
- But it could also increase
estrogen pretty potently?
- Yeah.
- And is it true that
increasing LH and/or hCG
can improve sensitivity of the genitals?
And is that true for men and women?
Yeah, I've heard this anecdotally.
People say hCG makes sexual
activity more pleasurable
for people because of some,
is it a direct effect on some
of the nerve cells in the genitals?
- Yeah, so LH is also an
agonist in the prostate
and in genital tissue in general.
So it's a very common treatment
for post-finasteride syndrome
or post-5-alpha reductase
when you've blocked the conversion of DHT
for a long time, it
helps re-upregulate DHT.
- So someone who's been taking finasteride
to prevent hair loss, comes off it,
maybe 'cause they felt lousy,
but then feels even lousier for reasons
that you talked about earlier.
And then they might use hCG
as a transition treatment
to transition back to
normal hormone health.
Is that right?
- Yeah.
- It's extremely helpful in many cases.
Now when you come off the hCG,
then you need to have a
strategy of how to return
to your normal as fast
as possible as well.
But it will upregulate those
5-alpha reductase enzymes.
You have, in your genital skin,
both scrotal skin and penile
skin, and perineum in general,
you have, I believe what's
called stratum lucidum.
It's skin layer that is very, very thin,
but it has the highest
concentration of 5-alpha reductase.
So you have a lot of activity.
And after you've been on something
that inhibits the enzyme,
the 5-AR enzyme in those tissues,
then you do something else
to upregulate those enzymes,
whether it's waiting and taking time,
whether it's trying tadalafil,
whether it's trying creatine even,
or whether it's trying HCG,
a lot of times those are the go-tos
for post-finasteride syndrome.
- Any risks for women
taking HCG on their ability
to get pregnant or risks generally?
- Yeah, obviously it'll make
any pregnancy test positive.
So that's a risk that
some women don't know.
- So one could, in theory,
fake a pregnancy test
by injecting hCG.
- Absolutely.
- Interesting.
- Yeah.
- I have no motivation to do that.
I was just curious.
[Kyle chuckles]
- Yeah.
- What about prolactin?
The simple version of
this that I was taught,
because I was taught mainly
from the neuroendocrine perspective was
dopamine is a kind of close
cousin of testosterone,
and also estrogen for that matter,
drives appetitive behaviors,
including pursuit of sexual
partners, sex itself,
motivated behaviors generally,
then postcopulatory, post-orgasmic states
are accompanied by a prolactin increase.
That's the refractory
period for mating in males,
and maybe even in females as well,
involved in milk letdown, et cetera.
What are sort of
the general contours of syndromes
or things that people
could be on the lookout for
of having too much prolactin
or too little prolactin?
And I'm aware of a number of people
who take dopamine agonists,
L-tyrosine, cabergoline,
things like that, to really
boost their dopamine levels.
And that isn't always a
good thing as it turns out.
Oftentimes people become
kind of hyper-dopaminergic
and so they have the drive
to do all these appetitive
things, fill in the blanks,
but they don't always have the ability,
because it seems,
just as testosterone
and estrogen need to be
in the proper ratios,
dopamine and prolactin need to
be in the appropriate ratios.
So how should we think about
and perhaps act on our prolactin systems?
- Absolutely, the way I describe it
is the dopamine wave pool.
So if you're increasing
your dopamine too much,
you're going to overflow and
then you're going to have
that wave crash too much.
So you want to have nice even waves
that are not going too far above the pool
of dopamine and prolactin will follow.
So prolactin and estrogen
are quite close cousins.
Estrogen upregulates a
gene called the PRL gene
or prolactin gene
that directly increases
prolactin synthesis.
So prolactin is going to also inhibit
the release of testosterone
from the pituitary.
So if you're using a dopamine agonist,
then you're to help decrease
the prolactin-producing cells,
including if you have a
prolactin-producing microadenoma
in the pituitary.
- How common are those?
Because, I mean, I hear a lot
about these hypogonadism or,
and of course that can be due
to an issue at the testicles
or hypergonadism could
also be of course in like
ovarian syndromes and
then there's of course
the brain side of it
where the signals aren't
coming from the brain.
Not enough gonadotropin, not
enough luteinizing hormone.
And there are ways of teasing this apart
with an endocrinologist
that are quite elegant
in fact, right?
Using stimulating hormones,
too much to dive into here.
But how often does one actually
have one of these pituitary tumors?
I have heard that people that play a lot
of high contact sport,
so boxing, football,
people that headed the
soccer ball quite a lot,
sadly people whose jobs force
them to take head blows for,
could be military.
And so they were firing 50 caliber guns
and the kind of woodpeckering of the brain
inside of the skull.
And construction workers
or just a concussion
can cause the pituitary
to go malfunctional.
Is that really common or
is this something that
is a rare like 1%?
- Yeah, it's extremely common.
It's another one of those conditions where
a lot of people never know they have it.
They just feel a little bit more fatigued.
They have that high prolactin
feeling all the time.
Pituitary microadenomas can
be non-producing as well.
So your prolactin can be totally normal.
Your growth hormone and
IGF-1 can be totally normal.
That's the second most common
producing microadenoma,
is growth hormone causing
either acromegaly,
which is growth of cartilage or gigantism.
- This is the big brow.
- Yeah.
- Yeah.
- So those are fairly
common causes of adenomas,
but a lot of people that
have a very small adenoma,
much less than one centimeter,
it's hard to see on imaging
even if you have a contrast
that specifically looks
at the pituitary and many
people aren't symptomatic.
So it's one of those
things along with PCOS
and pre-diabetes that
are much more frequent
when it comes to prevalence,
which is the amount,
the percentage of people that have it
in the general population.
- I'm glad you mentioned
the dopamine wave pool.
I know nowadays there's a lot of interest
in augmenting dopamine.
I know a number of people that do this
through prescription drugs,
Adderall, Ritalin, modafinil,
and those drugs of course
hit many transmitter systems,
but dopamine is certainly involved.
People taking antidepressants
like Wellbutrin tap
into that system.
And of course people are
trying to inhibit prolactin
and promote serotonin or reduce serotonin.
To me, it all seems like a
very delicate dance, right?
I mean, to just imagine the a arousal arc
for mating behavior,
for sexual reproduction,
is such an in an elaborate
dance between sympathetic drive
and parasympathetic drive,
even with across the
span of minutes, right?
I mean, I've talked about
this before on the podcast
that the arousal is kind
of more parasympathetic,
orgasm in itself is a
sympathetic response,
a completely different set of neurons.
And so where do you see
people getting into trouble
just trying to hit the
gas pedal on dopamine
and where do you think there is a place
for people who perhaps
are experiencing low drive
and motivation, not just
sexual, but in general,
to increase the amount
of dopamine circulating
in their brain and body?
How do you think about that,
given this wave pool analogy?
- Yeah, so it's important to parse it out
and start with the least
powerful interventions.
So if someone's concerned about dopamine
or maybe they have a
slightly higher prolactin,
then they eliminate things
that could be increasing that prolactin.
- Such as?
- Casein or gluten,
which are mu opioid receptor agonists
or any mu opioid receptor
agonist in the gut.
- Casein, so milk protein?
- Correct.
- Can increase prolactin?
- Correct.
- Interesting.
- In addition to that,
they should, if they need a pituitary MRI,
then they should get a pituitary MRI.
If they don't have an adenoma
or if they don't have a
high enough prolactin level
to where they need an MRI,
if they're having visual symptoms,
or if they're having olfactory
symptoms with the nose,
then it's more likely that they do.
But if they don't,
a lot of times a prolactin under about 40
is not too big of a deal.
They can take dopamine agonist
that agonize that D2 receptor
like P5P, which is essentially vitamin B6.
It's pyridoxine-5-pyrophosphate.
And pyridoxine is vitamin B6.
So that can help, 50
milligrams once to twice a day.
Vitamin E can also help,
especially if it's mixed to tocopherols.
A lot of people have
high levels of vitamin E,
but low levels of the
gamma form of vitamin E.
So that can also help.
- Fascinating, I'm so glad you
mentioned vitamin B6 and P5P.
I have heard
that one can shorten the refractory period
after orgasm, essentially to
be able to have sex again,
to be quite direct about it,
by way of vitamin B6 blunting
of the prolactin response,
which turns out to quite potent.
But I've also heard that
vitamin B6 can be neurotoxic,
especially in the periphery,
that it can cause peripheral neuropathies
if it's taken at high doses.
But that P5P is the safer form.
Is that true?
- It's pre-activated,
so it does not build up.
Think of it as a allegory
to how folate can build up.
It's not methyl folate,
but it builds up and it can
increase levels of homocystine.
Or if you have too much vitamin B12,
another water soluble B vitamin,
you can have too much
methylmalonic acid or MMA.
So depending on what your
enzymatic conversion is
to the active form of the enzyme,
often it's just safer to take
the active form of the enzyme.
- Yeah. Very interesting.
- Yeah.
- Okay, well, at risk of going
down every hormonal pathway
and talking about supplementation,
lifestyle factors,
I think touching on, as we have,
testosterone and estrogen,
and now prolactin,
I'd love to chat a little
bit about L-carnitine.
We talked about this earlier,
but I want to raise this
discussion about L-carnitine,
not in the context of L-carnitine itself,
but in the context of fertility.
Because my read of the
literature is that L-carnitine
can be very beneficial for
enhancing sperm quality
and egg quality and even
rates of conception.
What forms does L-carnitine come in
that people can reasonably consider?
Again, talk to your doctor, folks.
What is it doing?
And do we know how it's doing it?
And do you often use
this in your patients?
- Yeah, so the way I
think about L-carnitine,
and I'll try to tie this in with creatine,
and other things as well,
is if your cell is an
energy factory or car,
then L-carnitine is the
shuttle that helps get the fuel
into the motor to use the motor.
The motor is mostly due
to lifestyle factors.
So like your diet and your exercise.
And the type of fuel itself is NAD+.
We don't need to get into
NAD precursors or NMN
or NR, anything.
And then the accessory fuel
tank is your creatine phosphate.
So creatine is your accessory fuel tank.
Your NAD status,
which is largely determined
by your REM sleep
and quality sleep and exercise along
with supplementation as the fuel,
the carnitine shuttle is
carnitine palmitoyl coenzyme A.
And that takes medium-chain fatty acids,
it takes different molecules of fat.
You have two main energy
sources other than ketones.
You have your glucose or carbs.
You have your fat or fatty acids.
And that takes it across the
layer of the mitochondria
so that it can be utilized.
So upregulates that,
that's why things that
have flagella in general,
the flagella are going to
work better, like sperm.
- The flagella being anything,
sort of the wavy little
tenders on cell types
of which they're everywhere, right?
In the gut too, right, yeah.
- Yeah.
- Yeah.
- So those are going to
work significantly better.
And in general, you're mitochondria
are going to work better.
So the worst your
mitochondria are off the bat,
the better they're going to
be helped by these shuttle
that shuttles them across.
It also slightly increases the density
of the androgen receptor as well.
- Is that a local effect?
So if an L-carnitine is injected
into a particular muscle,
will it increase the density
of androgen receptors
in that muscle?
- Likely so.
- So how are people taking L-carnitine?
There are capsule forms and
there are injectable forms.
Most people are going to be
taking the capsule forms,
because that's all they're
going to have access to.
And then we should also ask,
can you get L-carnitine from food?
- Yeah, so L-carnitine
is just a combination of,
it's actually a very small peptide.
So glutathione is just
a three amino acids.
L-carnitine is the smallest peptide, two.
So peptide is just a
protein that has amino acids
between two and about 200.
And L-carnitine is just two amino acids.
- Amazing, so it's like a micro-peptide?
- Yeah, so your body synthesizes enough.
It likes to absorb the
amino acids by themselves.
And then if it puts them together,
there it makes L-carnitine.
It's not very bioavailable if you take it.
A lot of people take
L-carnitine, L-tartrate,
or a acetyl-L-carnitine,
and that's about 10% bioavailable.
So if you want 1 gram or 1,000 milligrams
of L-carnitine, you can take
10 grams of oral L-carnitine.
- Is the one gram the typical dose,
you recommend one gram per day?
- For fertility and androgen
receptor upregulation.
- So that means taking 10
grams of the capsule form?
- Yeah. So it's about 15 to
20 capsules, which is a lot.
- [Andrew] That is a lot.
- It can also potentially increase TMAO.
- Yeah, I want to ask about that,
because TMAO on your blood chart is,
when that's elevated,
that's going to cause some concern.
You taught me a trick,
however, that one can take 600
milligrams of garlic capsule
for the allicin.
Is that what it's called?
- Allicin is in it, yeah.
- It's like the name
Allison but with two L's?
- Yeah.
- Okay.
And that had a remarkable
effect in reducing TMAO.
So that's quite potent and also
was it just coincidence that
it really brought my LDL down as well?
- I'm not sure if the
LDL is a coincidence,
but depending on your gut
microbiome or your microbiota,
some microbiome beneficial bacteria
will convert carnitine and also choline.
So any choline precursor like Alpha-GPC
or phosphatidylserine,
it'll will convert them
more or less to TMAO.
So TMAO is something
that you can get measured
in a blood test and see
if it's high or low.
Some people might not even need allicin.
- Interesting.
- Some people
do benefit from it.
- Interesting, although I think it was you
that also told me
that allicin in garlic
can have positive effects
on cardiovascular tone
and blood flow generally.
Is that right?
- Yeah.
- Okay.
So is 600 milligrams
garlic an excessive amount
or can I just eat garlic?
- You can just eat-
- I mean,
I like eating garlic.
- Yeah.
- Yeah.
So, okay, so one could
also just eat garlic.
If one were going to take
L-carnitine in injectable form,
how much of that is bioavailable?
- 100% if you inject it.
It is in a aqueous solution,
so it's bacteria static water essentially.
So it's not in a carrier oil.
So it's going to burn a lot if
you inject it subcutaneously.
So it's going to be absorbed
faster and more evenly
and also just hurt a lot
less if you inject it
into a muscle.
- But one could then just
take one gram per day injected
or divide it up into a couple doses?
- Yeah, or 500,
the minimally efficacious
dose for injectable's probably
around 200 when it
comes to sperm motility,
the androgen receptor upregulation.
So it really depends on
why you're taking it.
- In terms of fertility,
and in terms of blood tests generally,
I always say that if possible,
either by way of insurance
or by way of some other way,
affording it, it would be great for people
to have blood tests
to know what their hormone
levels and other levels
of other things like metabolic
markers and lipids were
in their 20s, also in their
30s, also in their 40s.
I think there's this idea that
you only take a blood test
when you have a problem,
but then of course
one can't actually do the comparison
that you mentioned earlier
or state the comparison to one's physician
that things are changing over time.
And it seems to me that
basically everyone should get
at least a once-a-year blood test.
Is there the hope that insurance
will someday just cover it for everybody?
This will be standard care?
I would think that everybody
should know what sorts
of things are floating
around in their bloodstream
and what they need more
of and less of in life.
- I doubt it will ever
be covered by insurance.
In many cases,
you could make an argument
that it's indicated.
As insurance begins to cover more
of the population for pathologies,
the things like FSAs
or HSAs or care credit
will likely cover this advanced testing,
which it continues to come
down and down in price.
So it'll be affordable,
but it won't be free.
- Got it. Yeah.
I'd like to shift gears slightly
and talk about social interactions
and relational effects on hormones.
Something that I just find fascinating.
We touched on this a little bit earlier
in terms of oral contraception,
but now that we have the backdrop
of what these various hormones do,
some involvement in neurotransmitter
systems like dopamine
and pro prolactin and associated pathways.
Prolactin of course being a
hormone. Not a neurotransmitter.
But there's a phenomenon
in human beings where people
get very excited about
a new partner and
that excitement no doubt is related
to the dopamine system
among other systems.
And that excitement can be
maintained or can wane over time.
And here I'm talking about attraction,
but I'm also talking about
just general excitement
in the sense of novelty,
because that's what
dopamine's associated with.
Given that you work with human beings
and they have lives and
relationships and lifestyles,
and they have hormones, and
all these things interact,
what are some of the ways
that we could think about
adjusting our relationships
in order to optimize hormones
as opposed to just thinking
about how to optimize hormones
for sake of our relationship?
Because it's bidirectional of course.
And this assumes, I should say,
that one is already paying attention
to the six pillars talked about earlier,
that people are doing most things right.
How should we think about
relationships in hormones:
friendships, romantic relationships,
new partners, longterm partners,
yeah, how do you think
about this kind of stuff?
- Yeah, so if you have a new partner,
then it is largely regulated
by the dopaminergic system,
which changes over time.
So people may have heard
the saying that you have
to go through a full calendar year
with someone that you're in a relationship
so that you-
- Very good advice,
by the way.
- So that
you really know what to
do and what not to do.
But because you experience
both of your families
in the holidays and all
the different situations.
But I would argue until
you have moved in together,
had a baby,
and then raised that baby,
preferably breastfeeding,
because that's when you
get the prolactin spikes,
you haven't really gone through
every stage in life yet.
Now you can't really do
that with every person
that you're considering.
- Well, some people do,
but it can be quite
costly in terms of time
and finances and emotionally costly.
- Yeah.
- And then here, I'm
definitely not referring to
any personal experience
of having done all that many times over,
but what would you suggest people
do or think about as they
enter a relationship or
for people that are in
longterm relationships
where they feel like
something has shifted,
and indeed those shifts
may reflect the output
of different hormone systems
and neurotransmitter systems.
It almost certainly has
to be the case, right?
- Yeah, so just like women who
spend a lot of time together,
whether they're coworkers or whatever,
a lot of times their
menstrual cycles will align.
There is a lot of pheromonal
and hormonal crosstalk,
including prolactin between men and women.
So spending 100% of the time together,
this is why people think
it's so hard to work together
and live together.
They're around each other 24/7.
You don't have the reprieve where you let
that dopamine settle down,
and then you're excited
when you see them again.
A lot of guys know that if they've gone on
a hunting trip or if they've
gone on a trip for a long time,
they come back and they see their partner,
and it's like a new, not
quite like a new relationship,
but almost like a new relationship.
And they have that excitement again.
And purposely building that
into every relationship
can help significantly,
especially if you choose to
have a child or get pregnant
or be breastfeeding,
because you just plan ahead
for both of your prolactins
to be high and both of
your dopamines to be low.
And both of your testosterones to be low.
So there's a lot of
planning that you can do.
Essentially every relationship
goes through a crisis.
And that crisis is personal
between the two of you.
And you can plan ahead and
figure out a way, maybe
it's not supplementation.
Maybe it's not even the
amount of time you spend away
from each other.
But plan ahead to have good times
if you know you're about
to go into a crisis.
- Got it, and so it sounds like time apart
and time together,
which is actually built
into a number of cultures
where men and women
will purposefully avoid each
other for some period of time,
avoid physical touch
and maybe in proximity,
and then will reconvene,
and yet those are very stable
relationships over time often.
Is the inverse also true?
For instance, for people that are
in long distance relationships,
where they're only seeing each other three
or four days a week or two days a week,
does this explain the fact that
some of those relationships
can go on for a very long period of time
without ever actually entering the,
let's call it the hyper-prolactin phase
of actually moving in together
and et cetera, et cetera.
Like in other words,
is that a way in which people are spiking
and troughing dopamine
that keeps them attached?
This kind of elusive,
this sort of, what is it called?
I think it's called like a cat string.
Like if you play with a cat
and you move the string away,
they'll keep reaching,
but you throw the string on
the ground, they're like,
they're totally uninterested in it.
Is that what's going on?
'Cause that's a dopaminergic phenomenon,
the cat string example.
We know this experimentally.
- In those cases, the relationship
hasn't really progressed,
in many of those cases,
past the dopamine spike,
the fun initial stage, honeymoon stage,
whatever you want to call it.
So it's almost kind of like a roommate.
If you're looking for a roommate,
if it was for college or
after college or whatever,
you can fill out forms and
look for common interests,
but until you're actually together
a significant proportion of the time,
you're not really going to know
if you're going to be compatible or not.
- And is there evidence
that the appearance
of an infant changes,
obviously there're going
to be hormonal shifts.
We know actually that for
in both women and in men,
there's a prolactin increase
when couples are expecting a child.
It's almost like a brooding phenomenon.
You see this in birds where
it's actually called brooding
and it's caused by prolactin increase,
but it turns out this
also occurs in humans.
And some people would argue this causes
the dad bod phenomenon,
'cause it actually,
prolactin is involved in
laying down a body fat,
preparing for sleepless nights.
And presumably that spike
in prolactin is there also
to suppress sexual activity,
because there are periods
of time immediately
near childbirth where sexual
activity is not advantageous.
- Yeah, you see a prolactin
spike right after breastfeeding.
So if you think about it,
often when you have an infant,
you'll breastfeed, put the infant to bed,
and then immediately go
to bed with your partner,
which is not particularly conducive.
It's almost like trying to
have intercourse back to back.
And it's very difficult.
- Because of in the prolactin sense?
- Yeah.
- Yeah.
- Low dopamine, high prolactin.
Oxytocin is also increased significantly
to help with milk let-down as well.
So yeah, as far as brooding,
there's definitely a human
equivalent of brooding.
Some humans call it nesting
instinct, which is both helpful,
but it's not necessarily a
bad change in a relationship.
It's just a change.
And as long as you know that it's coming,
you're going to do better with it.
Just like any medication.
If you are aware of the side effect
and that it might happen,
then when it happens, it's not only
less severe, it also happens less often.
- Very interesting.
- If you tell the patient.
- Well as a neuroscientist,
I come from the framework that
of course hormones impact
perception and behavior,
but perception and behavior
also impact hormones.
I find this fascinating.
I also really like the example you gave
of people taking time apart,
but also these affiliative bonds
that are non-romantic bonds
can serve as kind of
a reservoir to replenish dopamine that
is then released upon
experience going back
to one's partner or some sort
of regular feature of home.
Very interesting, and of
course this should exist
on both sides.
I'm guessing that from both
the male side and female side,
there's an interest in kind
of separation and reunion
as the theme.
And I guess the frequency will vary for
different couples and
different situations.
- Yeah, and I don't want to
make it seem like prolactin
is all bad, so prolactin does help
with the nesting instinct.
It helps with breastfeeding as well.
A lot of women are diagnosed
with luteal phase defects,
which is basically the
phase after ovulation,
but before a period or giving birth.
A pregnancy's kind of a
prolonged luteal phase.
And a lot of them will go
on progesterone for this.
Progesterone can also decrease
prolactin and prolactin
is also helpful for the
maturity of lungs in infants.
So it helps the sphingomyelin
to lecithin ratio.
So if your prolactin's
too low through pregnancy,
it spikes up very high during pregnancy,
then it can lead to increased risk
of respiratory distress of the newborn.
- Really interesting. Yeah.
So we certainly don't
want to paint a picture
where prolactin is the
bad hormone to avoid.
Without proactive, none of
us would be here of course.
It's so vital.
I realized that earlier I raised
the question about whether
or not cold exposure could
modify hormone output,
in particular whether or
not ice baths or ice applied
to specific tissues of the
body, as people are doing,
one way or the other,
can change testosterone
levels, estrogen levels.
In other words, does taking
ice baths and cold showers
increase testosterone and/or estrogen?
- Yeah, so taking a ice
bath or a cold shower
or cold exposure in general,
it's not going to correct
a vitamin D deficiency
or a metabolic syndrome.
So there's a lot of things
that it will not correct
that are causes of hypogonadism
or low testosterone,
but it will help acutely,
specifically the application of cold
to testes that are too warm.
So if you have a varicocele
or if you have a little bit
of a primary hypogonadism,
which is where testosterone
is not released by the testes,
but your LH and FSH signals
are sufficiently high,
then you'll likely respond
to cold exposure better.
And there's actually undergarments that
are designed specifically
to help with fertility.
And there's probably going
to be more and more of that
in the future.
You just need to be careful
not to get frost bite,
because it's a particularly
bad spot to get frost bite.
- Noted. Could you define varicocele?
You've mentioned it a few times.
That's a varicose vein?
- Yeah, so it's essentially
a varicose vein.
It brings warm blood and the venous flow
or the flow back to the
heart is not as good.
Just like in the legs, it
can happen in the scrotum.
Usually about 20 to 25% of people
have one grade of varicocele.
There's grades one through
four, one through five.
And most people just have a very mild one,
usually on the left side
because the blood has
to go through further to
get back to the heart.
And it raises the
temperature of the testes.
Temperature is the enemy of testes.
So they like to be 5 to 10 degrees cooler
than the rest of the body.
- So are saunas particularly
bad for sperm production?
- They can be, yeah.
- When you say can be, I mean,
how long could one safely be in the sauna,
or would you want to go
back and forth between
the cold and sauna?
Are there any data?
- If someone is having infertility,
then I tell them to avoid
all saunas empirically.
If someone has, if they're not infertile,
but they have a low sperm count,
I also tell them to avoid.
However, it's mostly warmed water
that can raise the temperature
of the testes faster
than the sauna.
- So hot tubs and things of that sort?
- Yeah, so hot tub and a jacuzzi.
Those are enemies number
one and number two of sperm.
- What about ice baths and
cold showers for women?
Any evidence that it can
shift hormone output in women?
- Yeah, it can.
It increases the activity of
the beta adrenergic receptors,
even in the central nervous system
and the astrocytes as well.
So it can do a few things.
It can slightly decrease the
drive for food,
which astrocytes and beta
adrenergic receptors have,
some medications that
are weight loss medicines
also do similar things.
But it can be beneficial in women too.
- But no evidence that it
changes estrogen output
in women, correct?
- Not that I know of.
- No. Me either.
Peptides, lot of discussion
these days about peptides.
Peptides of course just
being strings of amino acids,
as you mentioned the very small ones like
two amino acids like L-carnitine
all the way up to polypeptides,
which just mean many amino acids.
There's so many peptides that
we should probably just do an
entire episode about peptides,
but I think one of the reasons I'm hearing
so much about peptides these days
is that they are not called steroids.
The name steroids I think
has come to be associated
with anabolic steroids
in the context of acne,
testosterone rage, et cetera.
But of course testoster, excuse me,
estrogen is a steroid hormone, right?
There are other steroid
hormones, as we both know.
But peptides are gaining
increasing popularity.
I am willing to go on record saying
that you can be sure that many
of the incredible
transformations that you see
in Hollywood are the
consequence of peptide use.
And I'd put
my name behind that because
I'm well aware of people
that use these to prepare for
roles, but athletes use them.
And then everyday people
are using them too.
For instance sermorelin,
tesamorelin, ipamorelin,
to stimulate the release of growth hormone
rather than taking growth hormone.
BPC-157, which is essentially
a synthetic gastric juice
that normally repairs the gut,
being used to treat injuries.
And there are other are ones as well.
What can we say generally
about peptides? Are they safe?
Are they not safe? What about sourcing?
And are there any peptides
that you think could be
of particular use for people?
And we should probably
also touch on peptides
that people shouldn't go anywhere
near with a 10-foot pole.
- Yeah, definitely, so peptides
are very heterogeneous.
There's very dangerous
ones and very safe ones.
My favorite peptide is
the original peptide,
which is insulin.
So insulin is a peptide and
less than 100 years ago,
there was a scientist studying insulin.
And at some point, they
saw that an animal had
its diabetes cured by
insulin inject, cured,
by insulin injection.
Less than a year later,
they were injecting insulin
into every type one diabetic,
because it was saving their lives.
- And yet insulin can kill you
if you take it at the incorrect dose?
- Yeah, so just like
insulin should be prescribed
by a doctor, there is
over-the-counter insulin,
ReliOn or NPH,
but ideally your insulin is
prescribed by your doctor
for your diabetes, as it's lifesaving.
Peptides should be prescribed
by doctors as well.
And there's several that are FDA approved.
So you mentioned a lot of different ones.
Let's start with tesamorelin.
So tesamorelin was recently FDA approved
for something called lipodystrophy.
It happens where body fat is
displaced into abnormal areas,
often as part of aids or
severe burns, things like that.
And it helps redistribute
this body fat and give people
their quality of life back.
Tesamorelin is a GHRH,
which I kind of loop into
the category of GHRPs,
so growth hormone-releasing peptides.
So it's only a couple
amino acids different
from endogenously-produced
growth hormone-releasing hormone.
So growth hormone itself
is also a peptide.
It's a peptide hormone.
Not a steroid hormone.
So you have
different somatotrophs
which are very similar
to growth hormone.
Another fun fact is that HPL,
which is human placental lactogen,
we love acronyms, right?
Human placental lactogen
is nearly identical
to growth hormone.
The growth hormone in pregnancy
is not what causes the sugar
spike in gestational diabetes.
It's the human placental lactogen.
So if you look at twin pregnancies,
if they have two placentas
or more placental tissue making
more human placental lactogen,
the risk of gestational diabetes
is exponentially higher.
So this HPL is only a
couple molecules different
from growth hormone.
It is interesting that
these different GHRHs
and GHRPs actually
have pretty different
mechanisms of action.
Ghrelin is also a hormone that's released
when you're hungry.
This is probably one of the reasons
why you have more growth
hormone release overnight.
And there's a lot of peptides
that are very similar
to ghrelin, so these peptides
are not bioidentical peptides,
but they just have a couple
different amino acids changed.
So they're almost identical
and they're probably going to
be used in the future for
growth hormone deficiencies,
including in kids, they've been studied.
- So if somebody wants
to increase their growth hormone output,
in addition to not eating
within two hours of sleep,
getting good, deep sleep,
doing all the other
things in the six pillars
that you mentioned earlier,
especially resistance exercise
at some point earlier in the day,
what are the risks and benefits of taking
a growth hormone-releasing hormone peptide
like sermorelin prescribed
by a doctor, of course.
What should one be concerned about?
How long could one take these?
I've even heard that they
can modify gene expression
so that they really are
changing your hypothalamus
in very long lasting ways.
- Yeah, there's definitely a lot of risk,
tumor growth and cancer.
So you look at a type one diabetic,
they have very high incidences
of various types of cancer.
They have very high growth hormone,
but low IGF-1 paradoxically.
So they would likely give
you a similar cancer risk
to a type one diabetic that
has very high growth hormone.
However, the benefits of it,
you think of lipolysis,
decreased body fat,
increased lean body mass.
A lot of those,
you can use other things
to get those benefits.
So then you don't need growth
hormone for those benefits.
It just leaves cosmetic benefit
to which you can usually
use topicals to get.
Your hair and your skin and your nails,
there's a lot of other
things that you can do
other than growth hormone.
So a lot of people just
don't need these GHRPs
if they don't have lipodystrophy
or if they don't have
growth hormone deficiency.
There is other uses of them,
specifically in injuries.
So I know that they've been studied,
I'm not sure if it's in the military.
We mentioned the woodpecker
or the contrecoup injury.
So that obviously.
- The head jolting back
and forth and the brain basically slamming
up against the front of the skull.
- So-
- Football, heading the ball
in soccer, definitely people who use
the 50 caliber in military,
although that's a fairly small population.
And I think anyone that's
hit their head hard
more than once.
- Yeah, we can talk
about BPC-157 for a bit,
GHK-copper peptide for a bit.
TB-500 or a thymosin beta-4 analog.
And then we can also
talk about bremelanotide,
which is melanotan III.
They have melanotan I and II,
and then they also have
melanotan III and IV.
- Yeah, let's talk about
BPC-157 and melanotan,
'cause I think those are the ones
that most people are eyeing, so to speak.
- Yeah, so BPC-157 is body
protective compound 157.
It's identical or bio-identical
to gastric protective compound 157
that's produced in the stomach.
So as you age, you get
atrophic gastritis very often.
That's why you have less intrinsic factor,
which is kind of another peptide
that binds to vitamin B12.
That's why you can get
age-related B12 deficiencies.
So that's one reason why
you have more colitis,
more or diverticulitis as you age.
You don't have that gastric
protective compound.
It increases VEGF vascular
endothelial growth factor,
which basically makes your
blood vessels grow more.
So that's what causes your
body to form a blood vessel.
So another medication known as Avastin.
It's on the WHO's list
of essential medications for cancer.
So many different types of
cancer, including colon cancer,
you treat it with Avastin,
which is a VEGF inhibitor.
So if you have cancer
or a high cancer risk,
you probably don't want
to be taking a medication
that's the exact opposite
mechanism of action
as your essential anti-cancer med.
- In other words, if you have cancer,
you're at risk of cancer, avoid BPC-157?
- Correct, a lot of people prescribe it
for six weeks and BPC-157,
so bremelanotide, that is FDA approved
for a hypoactive sexual disorder.
Tesamorelin, that's also
approved for lipodystrophy.
Interestingly another
one of the melanotans
is also approved for lipodystrophy.
And also deficiency in
the melanocortin receptor.
So the receptor that receives
the alpha-melanocyte-stimulating hormone,
it's a very rare condition.
It's also approved for that,
because if you don't take it,
then you get obesity.
But BPC-157 is not FDA approved,
but it is essentially standard
of care at this point.
I would say it's,
if you're not counting insulin
or growth hormone as peptides,
it's one of the most commonly
used peptides and anecdotally,
and in some clinical literature,
it's fairly well tolerated
for short periods of time.
I'm not in the camp that
everybody needs to do it two
to three times a week or even daily
for six weeks no matter what.
The major benefit is when you're
going to take it early on,
because it's going to allow
your body to increase blood flow
to the injured area, and
the less blood flow it has,
for example, cartilage, ligaments
have horrible blood flow,
especially as people age,
it's going to make a
significant difference.
So I would wager that that Russian gymnast
that achilles healed in one
month and completely from
a full rupture was likely taking BPC-157
or something very similar.
- Yeah, I'm willing to
wager on that as well,
a remarkable recovery.
And so because it is prescription,
there are non-prescription forms,
my understanding of the
non-prescription forms
and the danger of going
after non-prescription forms
is that oftentimes they will contain
what they claim they contain,
BPC-157 in this case,
but they are not adequately
cleaning out the LPS,
the lipopolysaccharide which
can cause inflammation.
In fact, in the laboratory,
we use LPS to deliberately
induce fever and inflammation
to study systemic inflammation.
So this is a warning to people.
If you're interested in peptides,
you absolutely need to
work with a physician,
in my opinion.
- Yeah.
- Get it from a really
good compounding pharmacy
that cleans out the LPS.
Because if you're buying
it through a source that
a lot of people, I don't
want to name sources,
but there are these common
sources on the internet
that everyone knows about.
They're buying these sources,
they'll ship it to anyone essentially.
But then the LPS is really
causing inflammation
and many people experience
a kind of mild fever
or tingling from that when they
inject it and they're like,
oh, I can feel it working.
That's probably LPS action,
which is not good for the brain.
I don't know about on
other peripheral tissues.
I haven't heard of people
dropping dead from this stuff yet,
but I certainly wouldn't
want to be ingesting
any LPs unnecessarily.
So would you agree that you
should work with a doctor?
After all you are a doctor.
- Yeah.
Definitely talk to your doctor about this
and talk to them about
dosing regimen as well.
So if they have you
doing it for six weeks,
ask 'em why am I doing it for six weeks?
Why not two weeks or why not
as soon as I feel better?
Can I just stop it?
Yeah, there's a lot of
good questions like that
that you should ask your doctor.
And if somebody's trying to prescribe you
a bunch of different things, then see,
is this what they prescribe everybody
or is this individualized for me?
There are peptides like GHK-copper peptide
which is produced
endogenously in the liver more
at younger ages.
That's why the liver can regenerate fully,
is this, the GHK-copper peptide helps.
And if you're copper deficient,
which not a whole lot of people are,
but a lot of people that
have had bariatric surgery
are copper deficient,
GHK-copper peptide can help significantly
with your nervous system.
And it's also synergistic.
So any growth agonist
like thymosin beta-4 made
in kids in the thymus, which shrinks.
That's another reason why
kids heal really well.
That and GHK is somewhat
synergistic with BPC,
but if you don't need all
three, you don't want them.
And if you don't need
it for more than a week,
you don't want it for more than a week.
- I really appreciate you saying that.
I often say that sometimes
the best dose of something
to take is zero.
It's often the case that
the best dosage is zero.
You mentioned melanotan.
There are several kinds of melanotan.
I find it a little bit
of a funny conversation,
because I first learned about melanotan
from reading about peptides
and discovering that people were
injecting melanotan to get tan,
because it's in the
melanin synthesis pathway.
They also discovered,
this isn't an individual.
This is reading about this
in various manuscripts
and peer-reviewed papers that
it could cause things like priapism,
like sustained erection,
that might be the last one
that anyone would ever have
because of damage to the vasculature.
Also women taking melanotan
as a way to get tan and lose body fat.
So this sounds all very recreational.
Are there any clinical usage of melanotan?
So separate from the kind
of extreme biohacking cosmetic world,
which is really not the main
focus of this podcast ever,
more in terms of health,
pursuing health optimization.
- Yeah, there's actually three
FDA approved indications,
believe it or not.
Not many people know about this,
but there's three well
accepted indications.
One of them is the
hypoactive sexual disorder,
and more in women,
that's for bremelanotide.
- So-
- Those are women
that have essentially
no libido whatsoever?
- Yeah.
- But other hormones are in check?
Yeah, classically it's before menopause.
So those hormonal issues
are not contributing.
And when you give them this peptide,
it's also known as PT-141,
it helps significantly.
A lot of times you use it in nasal spray.
It goes straight into the
central nervous system
and acts centrally.
You can also inject it,
and you can also take it via troche.
- Men and women take it?
- Correct. It's approved for women.
But it can also help men.
And it's relatively safe.
The only relative contraindication
that I tell people
and a lot of people say, oh,
there's no side effects that I know of.
But if you have a family
history of melanoma
or potentially have a melanoma
and don't know about it,
that's why I'm a big advocate
of dermoscopy as well
on regular skin checks,
then theoretically it's going to increase
that alpha-melanocyte-stimulating hormone,
and it can grow that.
So that's definitely not a good a thing.
So be very careful about
longterm administration of it.
It's also approved for lipodystrophy,
which is the same exact
thing as tesamorelin,
which I believe is also
known as Evista or Egrifta.
And then it's also approved
for the rare genetic condition
where your receptors or your
melanocytes don't proliferate
as well, so you usually
have hypopigmentation.
It's not true albinism,
but it's associated
with morbid obesity and
very be poor outcomes
from that in childhood, so
it's used in kids actually.
- Interesting, well, peptides
are a fascinating landscape,
but thank you for that deep
dive into several of them.
We will probably return to you
to talk about peptides
again in the near future,
because I know there's a lot more there.
And a lot of interest.
I want to talk about the
sixth pillar, all right?
So just to remind people,
you said diet, exercise,
where appropriate, caloric restriction,
managing stress, sleep
and sunlight are critical
for everyone at all ages to manage
and optimize hormone health.
Then you have the sixth category,
which is a really intriguing
one, which is spirit.
Which is kind of unusual
thing to hear coming
from a medical doctor,
except that I have many
colleagues and indeed our
former director of the
National Institutes of Health,
Francis Collins has talked
about this notion of spirit.
We've talked about belief effects
on this podcast before with Alia Crum,
how one's understanding
of the things that they do
and their world in general really creates
an important effect on everything
at the level of physiology,
not just psychology.
So as a physician,
how do you conceptualize
this spiritual aspect?
And how do you talk to
patients about this,
given that people walking into your clinic
presumably have a bunch
of different religious
and not a religious backgrounds.
I'm sure some are atheists.
Some are probably strong believers.
How do you deal with that?
And how should people think about this?
- Yeah, I believe it is
surprisingly well received.
You wouldn't think at first
glance that a patient really
wants to talk about their spiritual health
with their doctor,
but the way I think about it
and the way that it really is
is it's like a Venn diagram
and you have a body and a mind and a soul.
And you can't have one healthy
without the other healthy,
even if your mental health is phenomenal,
and even if your physical
health is phenomenal,
the mental aspect of spirituality,
if that piece is not there,
then that's going to affect your
body physiologically as well.
And Alia Crum's done some excellent work.
There's also been a lot of
other studies regarding prayer.
And I'm a Christian, I believe in God.
And that gives me a lot of
that resilience and motivation.
It gives me the cornerstone
or the groundwork,
how I can interact with life.
And regardless if someone's an atheist or
regardless of what someone
believes as far as religion
or the origin of the species,
they can know that their
spirituality is going to have
a profound effect on their mental
and physical health as well.
People like to compartmentalize it.
So they like to talk to
their doctor only about
the physical health 'cause
it's comfortable to do that.
They only talk to their pastor or a mom or
reiki healer for their spiritual health.
And they just talk to their therapist
or psychiatrist about their mental health.
But you need to bring all
three of those things together.
It's well known that
interdisciplinary clinics lead
to improved patient outcomes
and that's just disciplines
within medicine.
So that's just doctors
that are specializing
in this or this.
So this takes a step back
in the upper part of that tree
before you've reached those
dichotomies or the split-offs.
You have your body and
your mind and your soul,
so your spiritual health
and your mental health
and your physical health.
So if you're in line in
all three of those things,
that builds the cornerstone
for the rest of your health
and the rest of your life.
- So if someone comes into
your clinic and they say,
they're feeling one way in their body,
they're feeling one way
in their emotional life,
you run their charts,
you get their blood work,
and they're an atheist
or they're agnostic,
what are some of the
sixth pillar practices
that they can consider that are in keeping
with their atheism or agnosticism?
Because I have to assume that
people who are in participate
or feel that they belong to
a particular religious sex
will have particular prescriptives
from those religious sex
that will direct them towards
particular types of prayer.
But how would somebody who doesn't have
a prescriptive coming to
them from some other source,
what could they do or would they do?
- Yeah, so I certainly don't force prayer
on anybody or anything like that.
But it's my belief that being,
especially being an agnostic,
it's almost the hardest thing,
because if you're an atheist,
then you have some groundwork
and you have some spirituality,
even if it has to do with the
human spirits' interaction
with the environment,
things that can't be
physically explained well,
phenomenon like the work
that Alia Crum does.
But if you're agnostic, you're
still trying to find that.
So I hope that everybody does
find what they truly believe
in as far as their own spirituality.
But yeah, that's a personal journey.
From a physician's standpoint,
and even if I'm friends with them as well
from a friend's standpoint,
I don't like to push anybody
in any specific direction.
So I don't think that
everybody should believe
what I believe.
And I don't feel like there
should be any pressure
for them to believe something different.
So I think that there can
be excellent physician-patient rapport,
regardless of what we believe
and what our backgrounds are.
- Yeah. That's wonderful to hear.
I can say without revealing any names
that I have close colleagues that,
in every bin of this spectrum,
like hardcore atheists,
hardcore religious in different domains,
different religions, I don't know,
I don't know if I know many agnostic,
as to whether or not I know
any agnostics, I should say.
It's not something that
people commonly discuss,
but in the context of
science and medicine,
but it's starting to happen more and more.
And certainly this issue of spirituality
is one of the areas in
which neuroscience is asking
a lot of questions.
Like what spiritual experiences really are
in terms of how they're
grounded in the brain
or not grounded in the brain.
I think it's a really
interesting area for discovery.
And I appreciate that you bring it up,
and you bring it up in the
non-pressured way that you do.
I think that it will
stimulate a lot of thinking,
which is ultimately the
goal of this podcast.
Well, I have one final question that
a listener insisted I ask,
and it's a very straightforward one.
It's not at all a curve
ball and not at all related
to what we were just talking about.
But it was the most common
question when I told people
that I was going to be
talking to you, which is,
is caffeine problematic for hormones?
It's amazing, I received hundreds
of the same question about caffeine.
And since it's probably
the most commonly used drug
on the planet,
I know it's taking us back
into the very practical,
but in closing, we're not quite there yet,
but in closing is caffeine having
an effect, one way or the other,
on testosterone, estrogen,
or other hormones that is
positive, negative or neutral?
- Only if it affects your sleep.
So it works on adenosine
and it can actually slightly
improve allergies as well,
but negligible effects otherwise.
- Great.
- Yep.
- Well, sorry to end on
such a practical brass tacks
type of question, but I did
promise to the listeners
that I would ask that question.
Listen, I want to sincerely thank you.
We covered basically an
endocrinology textbook,
a neuroendocrinology textbook's
worth of information,
a ton of practical tips in there.
Where can people find out more about you?
We will certainly provide links.
And I guess the other question
is, are you taking patients?
I'm sure you'll hear that
in the various venues
where people can contact you.
But where are you active in
terms of public facing work?
- I'm active on Instagram, kylegillettmd.
I'm also active on the social
medias of my brand new clinic,
which is Gillett Health.
That's @GillettHealth on
Instagram or GillettHealth.com.
- Great. We'll provide links to those.
And I should say that
the content you've been
putting out on Instagram
is terrific because you actually pointed
to specific studies and you put things
into actionable context, which
is very meaningful for me.
Kyle, Dr. Gillett, I should say,
thanks so much for your time.
I really appreciate it and I
know the listeners will too.
- Thank you. My pleasure.
- Thank you for joining
me for my discussion
about hormone health and
optimization with Dr. Kyle Gillett.
As you just heard,
he is a treasure trove of
actionable clear information.
And again, you can find him
teaching more about hormones
and other aspects of health
on Instagram @kylegillett,
that's Gillett with two
T's and two L's, but no E,
kylegillettmd on Instagram
and Gillett Health on all other platforms.
And if you would like more
information about his practice,
you can find that at gilletthealth.com.
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During today's episode and
on many previous episodes
of the Huberman Lab Podcast,
we discuss supplements.
While supplements certainly
aren't necessary for everybody,
many people derive
tremendous benefit from them
for things like optimizing
sleep and focus,
and indeed hormone health.
Anytime you're considering
taking a supplement,
you want to make sure
that the supplements are
of the very highest quality.
For that reason, we've
partnered with Thorne,
T-H-O-R-N-E because Thorne
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which is not true for many
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If you'd like to see the
Thorne supplements that I take,
you can go to Thorne,
that thorne.com/u/huberman,
and you can get 20% off
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Also if you navigate deeper
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If you're not already following
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please do so.
It's Huberman Lab on both
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And there I cover science
and science-based tools,
some of which overlap with the contents
of the Huberman Lab Podcast,
but much of which is
distinct from the contents
of the Huberman Lab Podcast.
And again, we are hosting two live events.
One in Seattle on May 17th.
Another in Portland on May 18th.
That series is called
"The Brain Body Contract"
where I'll talk about science
and science-based tools,
some of which I have never
about in a public forum before.
And there will be an open
question and answer format
for you to ask me your questions,
and I will do my best to
answer them in real time.
Thank you once again for joining me
for today's discussion
with Dr. Kyle Gillett.
And as always, thank you for
your interest in science.
[energetic music]